Isoflavones, a type of phytoestrogen, are found in soy protein. Most traditional standard diets have soybean meal as a major ingredient, and therefore are a significant source of isoflavones. Please refer toFAQsection for more information about phytoestrogens.
In contrast, casein-based purified diets such as AIN-76A, AIN-93G, AIN-93M, and formulas with similar ingredients, are essentially free of isoflavones. This type of diet is sometimes used for research that requires a minimal isoflavone background. This type of diet can be used as the background to which isoflavones such as genistein (supplied by the customer) can be added.
An alternative to a purified, casein-based diet is a natural ingredient diet from our global rodent diet line. Several diets in this line contain minimal isoflavone/phytoestrogen levels and are commonly used for research that requires a minimal isoflavone/phytoestrogen background. This type of diet can also be used as the background to which isoflavones such as genistein (supplied by the customer) can be added.
Not all products are stocked locally; extended lead time and additional fees may apply. Many diets are available in certified format designated by a “C” following the product code. When diets are certified a representative sample is tested for a panel of contaminants. If not stocked as certified, certification can be made available upon request. Minimum order size and additional charges may apply.
The most common custom rabbit diets are those with a standard diet base and added cholesterol. Typically, the added cholesterol ranges from 0.25% to two percent. Additional fat can also be a feature of these formulas. To preserve pellet quality we recommend no more than six percent additional fat. Added fat is most often supplied as peanut oil, corn oil, coconut oil, or a combination. We recommend the Teklad base diets 2030 or 2031.
Rabbits do not readily consume purified diet. When specific nutrient manipulations are necessary, hybrid diets or at least some alfalfa meal inclusion is recommended. Contact us for formula examples or to discuss your specific needs.
Most often, customized diets for swine feature natural ingredients with added fat and cholesterol. Here are three variations on this theme:
TD.93296 Swine diet (15% lard, two perecent cholesterol)
We recommend these diets in meal/powder form, as pellets are not very durable. Other natural ingredient and purified diets with various nutrient manipulations are available. Contact us for further information.
The most common custom Guinea pig diets are those with a standard diet base (such as Teklad 2040 or 2041) and added cholesterol.
Guinea pigs do not readily consume purified diets, so when specific nutrient manipulations are necessary, hybrid diets (mixture of refined and natural ingredients) are recommended. At the very least it is advisable to retain some alfalfa meal in the diet. Contact us for further information.
Most times, diets that are developed for mice and rats are suitable for hamsters and gerbils, and vice versa. We may advise increasing specific nutrients in a purified diet for hamsters and gerbils. Contact us for further information.
Depending on the focus of your research, customized diet for non-human primates can contain natural ingredients, refined ingredients, or a mixture of both. Custom diets for primates often feature adjustments in fat type, fat level, and cholesterol. Contact us for further information.
At Envigo, we are dedicated to providing a broad range of research models and related services to the pharmaceutical and biotechnology industries, government, academia, and other life science organizations. We are committed to helping researchers realize the full potential of their critical research projects as we fulfill our mission to work together to build a healthier and safer world.
In order to build trust and confidence with our customers, we strive to consistently deliver scientific excellence. Included below is a list of our most recent certificates and accreditations.
Envigo RMS (Europe) — ISO 9001:2015 certificate The Production, Maintenance and supply of Laboratory Animals, Animal Diet, Biological Products, Surgically Modified Animals and the Production of Health and Genetic Monitoring
You may want to prepare your own diet at your research site or facility, and if that is the case, you depend on the ingredients being of the highest quality. Envigo can provide you with many of the same ingredients used to produce our advanced Teklad custom research diets so you can develop your own formula. And as always, our nutritional experts are here to help you make the best decisions for your ingredients and ultimate formulation.
Our ingredients
We offer several ingredients for individual sale so that you can develop your own blends.
“VFT” casein
“Vitamin-free” test casein (alcohol-extracted) is best suited for purified test diet formulas where fat or vitamin content needs to be precisely controlled
The reduced levels of many vitamins in VFT casein make it the preferred protein source for many vitamin studies. Thus, the nickname “Vitamin-free” was given to the extracted casein many years ago
Vitamin mixes
The common vitamin mixes shown below use sucrose or corn starch as a carrier
Customized vitamin mixes may use cellulose if a non-nutritive carrier is necessary
Vitamin mixes are formulated with a diet inclusion rate in mind. Using more or less than recommended could impair the health of your laboratory animal
For those preparing their own diets, vitamin premixes are an efficient way to add vitamins to a diet
Vitamin mixes should be stored at 4 degrees celsius or lower upon receipt. Storage at –20 degrees celsius is recommended if the mix will be used beyond 1 month
Minimum order is 500 g for both stock and custom vitamin mixes
Our available vitamin mixes are commonly used in diets, and are available from stock
Vitamin mixes are shipped within a few days of order
The common mineral mixes shown below as examples use sucrose as a carrier
Customized mineral mixes could use cellulose or no carrier if a non-nutritive carrier is necessary
Our mineral mixes are formulated with a diet inclusion rate in mind. Using more or less than recommended could impair the health of the animal
For those preparing their own diets, mineral premixes are an efficient way to add minerals to a diet
Mineral mixes should be stored in a dry cool environment and used within a year of receipt. The minimum order is 500 g for both stock and custom mineral mixes
These mineral mixes are commonly used in diets, and are available from stock
Our mineral mixes are shipped within a few days of order
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Envigo is a global company that is committed to helping customers realize the full potential of their products and research which contribute to enhancing the lives of people and animals, as well as protecting the environment. The value of animals in this critical research is essential for advancing our understanding of the body in health and disease and for developing new medicines and other compounds. Without animal research, we would not be able to produce the life-changing medicines that enhance and save lives across the world.
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A few vitamin adjusted formulas are shown below. Please contact us for additional formulas of this nature or for more information about altering the vitamin profile of a diet, and please read below to learn more.
Most vitamin deficient diets use vitamin-free test casein (VFT casein) as the protein source. VFT casein is casein that has been extracted with denatured alcohol to reduce the fat content from about 1% to 0.1%. In the process the content of a number of vitamins (present at low or trace levels in casein) is further reduced, making this an ideal protein source for these types of diets. Envigo produces our own VFT in-house, and we also offer this as an ingredient for those mixing their own diets.
From this vitamin deficient base, various levels of vitamins can be added back. Many formulas adjust multiple vitamins, and other nutrients.
If use of an intact protein source is not advisable, an amino acid defined diet can be used.
Contact us for other formula examples or to discuss your specific needs.
Purified high fat diets used to induce obesity and obesity-related complications such as diabetes and metabolic syndrome typically have 40-60% of energy derived from fat. The diet tables below summarize relevant diet features for several Teklad custom research diets commonly used in rodent models.
Teklad also creates high-fat diets for other species, including pigs, primates, and dogs.Contact usto discuss the use of these diets or one that better meets your needs.
Commonly-used diet-induced obesity (DIO) Teklad rodent diets with 55-60% of calories from fat
*Control diets can be designed in several ways, depending on what features the researcher wants to modify relative to the high-fat diet. These are just a few examples.
Commonly-used diet-induced obesity (DIO) Teklad rodent diets with 40-45% of calories from fat
Diets with 55-60% of calories from fat like TD.06414 and TD.93075 are commonly used for inducing obesity in rodents. While considered extreme compared to typical human fat consumption, these diets are effective in initiating rapid weight gain in most rodents. With higher fat content there is less room for carbohydrate, thus the carbohydrate (particularly sucrose) amount is relatively low compared to other obesity inducing diets. If you are interested in high fat and high carbohydrate, look at diets with 40-45% of calories from fat (often referred to as western diets).
As the fat level increases, pellet quality (durability) is often compromised. Some higher fat formulas are available only in non-pelleted form or require specific carbohydrate, maltodextrin, for pelleting. Depending on the fat and carbohydrate sources used, the non-pelleted form could be dense and crumbly, dough-like, or paste-like. Though a little more challenging to work with, non-pelleted diet is still used by many researchers for diet-induced obesity models as these researchers suspect the softer form may enhance obesity development.
Diets with 40-45% of calories from fat, like TD.95217 , TD.88137 , TD.06415 , and TD.08811 , represent another popular diet pattern for diet-induced obesity work. These diets have double or triple the amount of sucrose found in higher fat diets. High levels of simple carbohydrate like sucrose and fructose may help to promote hypertriglyceridemia, insulin resistance, and fatty liver. Diets with a pattern of high sucrose and high saturated or trans fat are often referred to as “Western Diets” in obesity and cardiovascular fields. Some “Western Diets” have further modifications to the fatty acid profile or even specific vitamin and minerals adjustments to be even more closely matched to a Western Diet pattern. For specific fatty acid modifications, see examples on our fat/lipid adjusted diets page.
Diets for diet-induced diabetes
Many of the same diets used for inducing obesity in rodents can be used to enhance diabetes related phenotypes like insulin resistance and glucose intolerance. However, fasting hyperglycemia characteristic of diabetes (glucose > 200 mg/dL) is uncommon with a diet only approach. Pre-feeding a high fat diet to induce a certain level of obesity and insulin resistance and then giving low-dose streptozotocin (STZ) may be an effective approach if overt hyperglycemia is desired.
Ingredient matched, low-fat DIO control diets
There are many options with different levels and types of fat in addition to different types of carbohydrate ranging from sucrose (highly refined, simple digestion) to corn starch (refined, but more complex) to resistant starch (refined, but not fully digestible). A very basic purified control diet would be AIN-93M (TD.94048 ) or AIN-93G (TD.94045 ). AIN-93 diets have a moderate amount of sucrose at ~10%, and fat is from soybean oil with a healthy fatty acid profile. Additional examples of controls for specific DIO diets can be found in the above tables. Learn more about AIN diet formulas.
Many researchers choose to compare their high fat fed animals to animals fed a natural ingredient, grain-based diet (also referred to as standard diets or chow). These diets differ in the source and level of nutrients as well as in the presence of non-nutritive factors (such as phytates or phytoestrogens). Depending on what your main comparisons are, it may be suitable to have a grain-based diet as your control/reference group. However, making such comparisons limits inferences to dietary patterns versus a specific dietary component.
Enrichment products enhance the welfare of research animals. Inotiv offers a number of enrichment products, making Inotiv your one-stop supplier for lab animal diets, bedding and enrichment.
Not all products are stocked locally; extended lead time and additional fees may apply. Many diets are available in certified format designated by a “C” following the product code. When diets are certified a representative sample is tested for a panel of contaminants. If not stocked as certified, certification can be made available upon request. Minimum order size and additional charges may apply.
The raw stock for our corncob bedding products is 100% corncob. No other components or additives are used. The 1/4″ (7097) and 1/8″ (7092) products are produced from only the woody-ring portion of the corn cob, and the pelleted corncob is produced from the pith and chaff (beeswing) portions.
As the raw stock corncobs are introduced to the plant, they pass through a hammermill that produces corncob fractions. The corncob fractions are then heat-dried. The drying process utilizes a rotary dryer systemthat heats the corncob fractions to approximately 200 degrees fahrenheit for two to three minutes. An aspiration process separates the woody-ring portion of the corncob from the pith and chaff portions. Smaller fractions/particles are produced by rollermill and hammermill processes. The particles are then sized and separated through a sifting process which utilizes screens conforming to U.S. standards. The particles pass through a final aspiration process to remove any remaining dust and aspiration process to remove any remaining dust and are then placed in overhead storage until packaged. The pith and chaff portions are processed through a pellet mill to produce the pelleted corncob product. Plant operating procedures require a minimum testing frequency of twice per shift for measuring moisture content and particle size distribution.
Listed below is information on average particle size and absorption rates.
7092 — 1/8″ corn cobs, 40 lbs.
7092A, Autoclavable — 1/8″, corn cobs, 40 lbs.
7902.25 Irradiated — 1/8″ corn cobs, 25 lb. cap sacks
7902,CS Irradiated — 1/8″ corn cobs, four by seven lbs./case
7097 — 1/4″ corn cobs, 40 lbs.
7097A Autoclavable — 1/4 ” corn cobs, 40 lbs.
7907.25 Irradiated — 1/4″ corn cobs, 25 lb. cap sacks
7907.CS Irradiated — 1/4″ corn cobs, four by seven lbs./case
These formulas are purified diets with commonly used refined ingredients. These basic formulas are often modified for a specific research purpose, such as altering the fat source, a vitamin or mineral level, or adding a compound. See theFAQsection to learn more about the history of these formulas, AIN-76A, AIN-93G, and AIN-93M.
These formulas (as well as other purified diets) do not contain alfalfa and can be used to reduce background autofluorescence in certain imaging applications. Our Global Rodent Diets are also alfalfa-free and are suitable for imaging work. Please contact us for further information about these formulas or modifications.
Other related product codes:
TD.94096 version of AIN-76A suitable for irradiation (vitamin levels are increased)
TD.97184 version of AIN-93G suitable for irradiation (vitamin levels are increased)
TD.00102 version of AIN-93M suitable for irradiation (vitamin levels are increased)
TD.95092 modification of AIN-93G where soybean oil is replaced with corn oil
When your experiments require the addition or application of certain compounds to your animal research subject, you can consider adding your medications or compounds to your animal’s diet. Envigo has experience customizing diets for all types of research needs, and that includes introducing additives as a convenient way to medicate lab animals. Simply turn to one of our expert staff nutritionists to determine whether it is a viable option.
Medications or compounds supplied by your investigator are referred to as “customer supplied ingredients” or “customer reserves,” and they can be added to most diets. Generally, if the stability or activity of the compound is not compromised during manufacture or further processing such as irradiation, adding an ingredient can be a smart option for simplifying your feeding and medicating schedules. Also, the inclusion rate of any given compound is adjusted to suit your needs, and can be determined in consultation with our expert nutritional staff.
Please use the customer supplied ingredients submission form if you require the addition or application of certain compounds to your animal research subject.
When adding a compound to a diet, we will work with you to be sure that it is appropriate for our diet formulation procedures and can be done safely.
We require a safety data sheet or other relevant safety and usage information
We have an obligation to maintain a safe work environment. This typically applies to drugs, experimental compounds and chemicals
Food products generally will not require safety information, although information about nutrient content, reason for use, etc. is helpful in the design of diets
Water is added as a pelleting aid. Pellets are formed under pressure but no external heat is applied
Sometimes the drying process can be modified if heat stability is questioned
It is your responsibility to determine the suitability of the compound for inclusion into a pelleted diet
If you require irradiation, we can customize most diets to be suitable for this sterilization process
Once your diet has been produced, we can send it for irradiation. The dose ranges from 20-50 kGy. Diets that are to be irradiated require an additional two weeks for shipment (four weeks total)
For diets that are to be irradiated, vacuum packaging may be beneficial. Both irradiation and vacuum packaging must be requested when ordering
We defer to you to determine the suitability of the compound for irradiation
Inform us on a g/kg diet or percentage basis, how much of the compound you want in the diet
If you need to calculate a dose based on animal body weight, we can help convert that to g/kg diet
Depending on the choice of base diet and the nature of the added ingredient(s), more than a ten percent dilution is generally not advisable
To limit differences between the control and experimental diets you may want to consider using a control diet that uses similar ingredients and has gone through the same production process
Send extra compound (approximately enough for one more kg than you have ordered) so that we can yield the desired amount of diet
If we have not received enough compound, we will use the entire amount and make as much diet as possible, unless special arrangements can be made
If you plan to use the compound more than once and stability with storage is not an issue, we can maintain an inventory for you and store it appropriately, per your instructions
Unless otherwise instructed, we will return any remaining compound with your shipment, but we do not dispose of the compound
If you would like your compound retained for future use, please supply us with a retention document
Dietary methods to induce NAFLD/NASH in rodents can be split into two common categories:
diets fed for longer periods of time to induce obesity, metabolic syndrome, and mild NASH or
diets fed for short periods of time to induce hepatic features of severe NASH without inducing obesity or insulin resistance
This page provides further information on dietary methods to induce NAFLD/NASH. We’ve also prepared a downloadable NASH/NAFLD mini paper.
The tables below highlight diet options from both of the above categories. For more complete descriptions of NAFLD/NASH models see the drop down menus that follow the tables.
Diet options for inducing obesity, metabolic syndrome and mild NAFLD/NASH
Diets inducing obesity, metabolic syndrome and mild NAFLD/NASH
Western and Fast Food diets with milkfat and cholesterol
Western or fast food style diets fed to induce NASH with metabolic syndrome contain 40 – 45% kcal from milkfat (a fat source high in palmitate) with added cholesterol (0.15 – 2%) and are high in sucrose (>30%). Dietary palmitate and cholesterol have both previously been associated with the progression from simple steatosis to NASH.
These diets can induce obesity, metabolic syndrome, and simple steatosis within nine weeks of feeding. Increased hepatic inflammation has been observed after 12 weeks of feeding. NASH typically requires longer feeding with fibrosis developing within nine months and late stage fibrosis including hepatic ballooning occurring after 14 – 20 months of feeding. Increasing dietary sucrose (~41%) and cholesterol (~1.25%) accelerates the NASH phenotype with steatosis, inflammation and hepatocyte ballooning observed within 12 weeks. In addition to feeding a high fat diet, providing a glucose/fructose mixture in the drinking water may further promote NASH development.
Select References:
Charlton, M., et al., Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition. Am J Physiol Gastrointest Liver Physiol, 2011. 301(5): p. G825-34. www.ncbi.nlm.nih.gov/pubmed/21836057
Gores, G., Charlton M, Krishnan A, Viker K, Sanderson S, Cazanave S, McConico A, Masuoko H. Am J Physiol Gastrointest Liver Physiol, 2015. 308: p. G159. ajpgi.physiology.org/content/308/2/G159
Li, Z.Z., et al., Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-CoA desaturase. J Biol Chem, 2009. 284(9): p. 5637-44. www.ncbi.nlm.nih.gov/pubmed/19119140
Ioannou, G.N., et al., Hepatic cholesterol crystals and crown-like structures distinguish NASH from simple steatosis. J Lipid Res, 2009. 54(5): p. 1326-34. www.ncbi.nlm.nih.gov/pubmed/23417738
Alkhouri, N., et al., Adipocyte apoptosis, a link between obesity, insulin resistance, and hepatic steatosis. J Biol Chem, 2010. 285(5): p. 3428-38. www.ncbi.nlm.nih.gov/pubmed/19940134
Dixon, L.J., et al., Caspase-1 as a central regulator of high fat diet-induced non-alcoholic steatohepatitis. PLoS One, 2013. 8(2): p. e56100. www.ncbi.nlm.nih.gov/pubmed/23409132
DeLeve, L.D., et al., Prevention of hepatic fibrosis in a murine model of metabolic syndrome with nonalcoholic steatohepatitis. Am J Pathol, 2008. 173(4): p. 993-1001. www.ncbi.nlm.nih.gov/pubmed/18772330
VanSaun, M.N., et al., High fat diet induced hepatic steatosis establishes a permissive microenvironment for colorectal metastases and promotes primary dysplasia in a murine model. Am J Pathol, 2009. 175(1): p. 355-64. www.ncbi.nlm.nih.gov/pubmed/19541928
Asgharpour, A., et al., A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer. J Hepatol, 2016. 65(3): p. 579-88. www.ncbi.nlm.nih.gov/pubmed/27261415
Tetri, L.H., et al., Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. Am J Physiol Gastrointest Liver Physiol, 2008. 295(5): p. G987-95. www.ncbi.nlm.nih.gov/pubmed/18772365
Tsuchida, T., et al., A simple diet-and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer. Journal of hepatology, 2018. 69(2):385-395. www.ncbi.nlm.nih.gov/pubmed/29572095
The ALIOS model: western diet with trans-fat
The American Lifestyle-Induced Obesity Syndrome (ALIOS) model involves feeding the “American fast food” diet high in trans-fats and sugar. Dietary trans-fats from hydrogenated vegetable shortening (HVO) are associated with increased insulin resistance and hepatic inflammation in rodent NASH models. In addition to diet, a glucose/fructose solution is added to the drinking water and sedentary behavior promoted by removing the overhead cage feeders in this model.
The ALIOS model develops obesity with insulin resistance, elevated ALT levels, and steatosis within 16 weeks. Increased inflammation and early development of fibrosis have been observed at 6 months. Severe steatosis with fibrosis and inflammation develops within 12 months of feeding with 50% of the mice reportedly developing hepatic neoplasms. Adding cholesterol (0.2%) to the American Fast Food diet may accelerate NASH phenotype development.
Select References:
Koppe, S.W., et al., Trans fat feeding results in higher serum alanine aminotransferase and increased insulin resistance compared with a standard murine high-fat diet. Am J Physiol Gastrointest Liver Physiol, 2009. 297(2): p. G378-84. www.ncbi.nlm.nih.gov/pubmed/19541924
Tetri, L.H., et al., Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. Am J Physiol Gastrointest Liver Physiol, 2008. 295(5): p. G987-95. www.ncbi.nlm.nih.gov/pubmed/18772365
Mells, J.E., et al., Glp-1 analog, liraglutide, ameliorates hepatic steatosis and cardiac hypertrophy in C57BL/6J mice fed a Western diet. Am J Physiol Gastrointest Liver Physiol, 2012. 302(2): p. G225-35. www.ncbi.nlm.nih.gov/pubmed/22038829
Dowman, J.K, et al., Development of hepatocellular carcinoma in a murine model of nonalcoholic steatohepatitis induced by use of a high-fat/fructose diet and sedentary lifestyle. Am J Pathol, 2014. 184(5):1550-1561. www.ncbi.nlm.nih.gov/pubmed/24650559
Mells, J.E., et al., Saturated fat and cholesterol are critical to inducing murine metabolic syndrome with robust nonalcoholic steatohepatitis. J Nutr Biochem, 2014. 26(3): p. 285-92. www.ncbi.nlm.nih.gov/pubmed/25577467
FPC diet: fructose, palmitate, cholesterol and trans-fat diet
The Fructose, Palmitate, Cholesterol and Trans-Fat (FPC) diet is a recent NASH diet that includes Western and ALIOS model diets to achieve both metabolic and hepatic NASH features within an accelerated time frame. Key features of the FPC diet include 1) a lower Met content than typical rodent diets by decreasing total protein without supplementing sulfur amino acids; 2) choline supplementation is lower than typical but is not considered deficient; 3) high in sucrose (~34% by weight); 4) 1.25% cholesterol; 5) 52% kcal from fat with fat sources including milkfat fat, palmitic acid and hydrogenated vegetable shortening to provide trans-fats. Like the ALIOS model, the FPC model also provides a glucose/fructose solution to the drinking water.
Male C57BL/6J mice fed the FPC diet and provided a glucose/fructose drinking solution developed insulin resistance and NAFLD with inflammation, hepatocyte death, and fibrosis within 16 weeks.
Select References:
Wang, X., et al., Hepatocyte TAZ/WWTR1 promotes inflammation and fibrosis in nonalcoholic steatohepatitis. Cell Metab, 2016. 24(6): p. 848-62. www.ncbi.nlm.nih.gov/pubmed/28068223
Zhu, C., et al., Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis. Sci Transl Med, 2018. 10(468). www.ncbi.nlm.nih.gov/pubmed/30463916
High fat diets
Common diets to induce obesity (DIO) can be fed to induce uncomplicated NAFLD. These high fat diets typically contain 40–60% kcal from fat without supplemented cholesterol or cholate. Simple sugars such as sucrose or fructose can also be supplemented via diet or water to progress the fatty liver phenotype. Diets can be in pellet or powder/dough form depending on the formula. Some models require limited physical activity and in those cases diets can be fed inside the cage. For more information see our Diet Induced Obesity page.
In susceptible rodent models, high fat diets are commonly used to induce NAFLD with obesity and insulin resistance common metabolic features associated with NASH in humans. However, the degree of NASH pathology (steatosis, inflammation, and fibrosis) is limited or mild and varies depending on the animal model, length of feeding, and dietary components.
Diets to induce severe hepatic NAFLD/NASH without obesity or metabolic
Atherogenic diets high in fat, cholesterol, and cholate
Originally formulated to induce mild atherosclerosis in wild-type rodents, high fat diets containing added cholesterol (1 – 1.25%) and cholate (0.5% as sodium cholate or cholic acid) have also been useful in inducing NASH. This diet option includes purified “Western” style diets with increased cholesterol and cholate and also hybrid diets. Hybrid diets were originally developed by Beverly Paigen and colleagues by mixing a natural ingredient mouse diet in a 3:1 ratio with a concentrated purified diet (containing 5% cholesterol and 2% sodium cholate) resulting in a diet containing ~15.8% fat, 1.25% cholesterol, and 0.5% sodium cholate. Although a less refined approach, the hybrid diet is associated with increased gallstone formation and liver damage as compared to similar purified diets.
Atherogenic diets are able to induce varied degrees of NASH with increased hepatic inflammation with early fibrosis observed after ten weeks of feeding. However, the metabolic profile typical in human NASH (obesity with insulin resistance) is not recapitulated in this model with animals typically maintaining similar body weights as control fed groups without the development of metabolic syndrome.
Select References:
Nishina, P.M., J. Verstuyft, and B. Paigen, Synthetic low and high fat diets for the study of atherosclerosis in the mouse. J Lipid Res, 1990. 31(5): p. 859-69. www.ncbi.nlm.nih.gov/pubmed/2380634
Kamari, Y., et al., Lack of interleukin-1alpha or interleukin-1beta inhibits transformation of steatosis to steatohepatitis and liver fibrosis in hypercholesterolemic mice. J Hepatol, 2011. 55(5): p. 1086-94. www.ncbi.nlm.nih.gov/pubmed/21354232
Kim, D.G., et al., Non-alcoholic fatty liver disease induces signs of Alzheimer’s disease (AD) in wild-type mice and accelerates pathological signs of AD in an AD model. J Neuroinflammation, 2016. 13: p. 1. www.ncbi.nlm.nih.gov/pubmed/26728181
Madrigal-Perez, V.M., et al., Preclinical analysis of nonsteroidal anti-inflammatory drug usefulness for the simultaneous prevention of steatohepatitis, atherosclerosis and hyperlipidemia. Int J Clin Exp Med, 2015. 8(12): p. 22477-83. www.ncbi.nlm.nih.gov/pubmed/26885230
Savransky, V., et al., Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver. Am J Physiol Gastrointest Liver Physiol, 2007. 293(4): p. G871-7. www.ncbi.nlm.nih.gov/pubmed/17690174
Methionine/choline deficient (MCD) diets
Methionine and choline deficient (MCD) diets are amino acid defined rodent diets deficient in methionine and choline, high in sucrose (>40% by weight) with ~10% corn oil by weight. Methionine and choline deficiency decreases fat oxidation and export of fat from the liver. Dietary sucrose is necessary for hepatic lipid accumulation and oxidation. The polyunsaturated fat in corn oil promotes hepatic lipid oxidation.
Steatosis, increased serum alanine aminotransferase (ALT), inflammation, and hepatic fat oxidation has been observed within three weeks of feeding the MCD diet with fibrosis development after six weeks. This dietary model does not produce metabolic syndrome (an aspect of NASH in human models) and progressive weight loss (up to 40%) is associated with the MCD diet feeding.
Select References:
Pickens, M.K., et al., Dietary sucrose is essential to the development of liver injury in the MCD model of steatohepatitis. J Lipid Res, 2009. 50(10):2072-82. www.ncbi.nlm.nih.gov/pubmed/19295183
Li, Z.Z., et al., Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-CoA desaturase. J Biol Chem, 2009. 284(9): p. 5637-44. www.ncbi.nlm.nih.gov/pubmed/19119140
Lee, G.S., et al., Polyunsaturated fat in the methionine-choline-deficient diet influences hepatic inflammation but not hepatocellular injury. J Lipid Res, 2007. 48(8): p. 1885-96. www.ncbi.nlm.nih.gov/pubmed/17526933
Vetelainen, R., A. van Vliet, and T.M. van Gulik, Essential pathogenic and metabolic differences in steatosis induced by choline or methione-choline deficient diets in a rat model. J Gastroenterol Hepatol, 2007. 22(9): p. 1526-33. www.ncbi.nlm.nih.gov/pubmed/17716355
Leclercq, I.A., et al., Intrahepatic insulin resistance in a murine model of steatohepatitis: effect of PPARgamma agonist pioglitazone. Lab Invest, 2007. 87(1): p. 56-65. www.ncbi.nlm.nih.gov/pubmed/17075577
Kashireddy, P.R. and M.S. Rao, Sex differences in choline-deficient diet-induced steatohepatitis in mice. Exp Biol Med (Maywood), 2004. 229(2): p. 158-62. www.ncbi.nlm.nih.gov/pubmed/14734794
Dixon, L.J., et al., Caspase-1-mediated regulation of fibrogenesis in diet-induced steatohepatitis. Lab Invest, 2012. 92(5): p. 713-23. www.ncbi.nlm.nih.gov/pubmed/22411067
Emerging NASH models
Dietary models of NAFLD/NASH continue to evolve with the goal of more accurately recapitulating both the metabolic and hepatic symptoms of human disease. Commonly researchers are studying the synergistic effects of various NASH dietary features to accelerate progression of the model and severity of liver disease.
A Teklad nutritionist can work with you to formulate new diets in order to investigate novel dietary models of NAFLD/NASH. Contact a nutritionist at askanutritionist@envigo.com for a diet consultation.
Control diets
The choice of control diet is dependent on the specific research goal. Many researchers choose to compare their NAFLD/NASH diet-fed animals to animals fed a natural ingredient, grain-based diet (also referred to as standard diet or chow). These diets differ in the source and level of nutrients as well as in the presence of non-nutritive factors (such as phytates or phytoestrogens).
Depending on what your main comparisons are, it may be suitable to have a grain-based diet as your control/reference group. However, making such comparisons limits inferences to dietary patterns versus a specific dietary component. In some cases, such as those studies feeding amino acid defined diets like the MCD model, a matched control diet is recommended given the very different formulations and protein sources of grain-based diets.
When making inferences about specific nutrients within the diet an ingredient matched, low fat control diet may be necessary. There are many options with different levels and types of fat in addition to different types of carbohydrate ranging from sucrose (highly refined and digestible) to corn starch (refined, but more complex) to resistant starch (refined, but not fully digestible).
A very basic purified control diet would be AIN-93M TD.94048 or AIN-93G TD.94045 . AIN-93 diets have a moderate amount of sucrose at ~10% with fat from soybean oil providing a healthy fatty acid profile. Learn more about AIN diet formulas.
Contact a nutritionist for an additional information and control diet recommendations.
Need more information? A Teklad nutritionist will work with you to determine if existing diets will meet your needs or formulate new diets to help you investigate novel dietary models of NAFLD/NASH. Contact us for a diet consultation.
Diet can be a useful tool to induce or accelerate atherosclerosis in laboratory animal models. Key dietary features used to induce atherosclerosis in rodents vary depending on the research model, desired endpoint, and length of feeding. While formulations of atherogenic diets continue to evolve, the options that are well-described in the literature are summarized below. For more information on each diet option and literature references see the expandable tabs following the diet table.
Research use
Key dietary features
Examples
“Western” purified atherogenic diet
Accelerated hypercholesterolemia and plaque formation in genetically modified models such as Apoe and Ldlr deficient mice.
Used for diet induced obesity in a variety of rodent models.
High fat diet (20 – 23% by weight; 40 – 45% kcal from fat)
Saturated fatty acids (SFA >60% of total fatty acids)
*Sodium cholate or cholic acid aid cholesterol and fat absorption and reduce cholesterol disposal via bile acid synthesis. However, if including a cholate source is not desired for your research, diets without cholate are available.
“Western” purified atherogenic diet
“Western” style diets are fed to genetically-modified cardiovascular models, such as Apoe and Ldlr deficient mice, to accelerate and enhance hypercholesterolemia and plaque formation and to elicit phenotypes commonly associated with metabolic syndrome. Within the atherogenic literature, a “Western” diet typically is described as a purified rodent diet with 20-23% milkfat/butterfat, 0.2% total cholesterol, and 34% sucrose by weight. TD.88137 is an example of a “Western” style diet that was originally designed to characterize and enhance atherosclerosis development in a newly generated Apoe-deficient mouse model. Contact us for more information about “Western” style diets, modifications, or possible control diets.
Examples:
TD.88137 Adjusted calories diet (42% from fat, 0.2% total cholesterol)
TD.10885 45% fat Kcal diet (0.2% total cholesterol)
Research use:
Accelerated hypercholesterolemia and plaque formation in genetically-modified models, such as Apoe and Ldlr deficient mice.
Used for diet-induced obesity in a variety of rodent models.
Key dietary features:
High Fat Diet (20-23% by weight; 40 – 45% kcal from fat)
Saturated fatty acids (SFA >60% of total fatty acids)
Milkfat/butterfat
Sucrose (34% by weight)
Cholesterol (0.2% total)
References:
Febbraio, M., et al., Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J Clin Invest, 2000. 105(8): p. 1049-56.
Huszar, D., et al., Increased LDL cholesterol and atherosclerosis in LDL receptor-deficient mice with attenuated expression of scavenger receptor B1. Arterioscler Thromb Vasc Biol, 2000. 20(4): p. 1068-73.
Nakashima, Y., et al., ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb, 1994. 14(1): p. 133-40.
Nakashima, Y., et al., Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse. Arterioscler Thromb Vasc Biol, 1998. 18(5): p. 842-51.
Plump, A.S., et al., Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell, 1992. 71(2): p. 343-53.
Towler, D.A., et al., Diet-induced diabetes activates an osteogenic gene regulatory program in the aortas of low density lipoprotein receptor-deficient mice. J Biol Chem, 1998. 273(46): p. 30427-34.
Tsuchiya, K., et al., FoxOs integrate pleiotropic actions of insulin in vascular endothelium to protect mice from atherosclerosis. Cell Metab, 2012. 15(3): p. 372-81.
“Western” purified atherogenic diet with added cholesterol and cholate source*
Wild type mice and rats generally are resistant to atherosclerosis, requiring more extreme dietary manipulation to modify lipoprotein profiles and develop mild atherosclerosis (foam cells, fatty streaks). Modern formulations are made completely of purified ingredients because this more refined approach has been reported to decrease the incidence of gallstones and liver damage associated with less refined and more traditional dietary approaches. To induce mild atherosclerosis in wild type animals, the “Western” purified diet can be modified to increase cholesterol (1-1.25%) and add a bile salt such as sodium cholate or cholic acid. Contact us for more information, modifications, or possible control diets.
Examples of purified high fat diets with added cholesterol and cholate source*:
Induce hypercholesterolemia and mild atherosclerosis (foam cells, fatty streaks) primarily in wild type mice and rats.
Will not promote obesity.
Key dietary features:
High fat diet (15-20% by weight; 34 – 45% kcal from fat)
Saturated fatty acids (SFA >55% of total fatty acids)
Milkfat/butterfat, cocoa butter
Sucrose (30-50% by weight)
Cholesterol (1 – 1.25%)
Cholate source (0.5%)*
References:
Bernal, C., et al., Lipid biomarkers and metabolic effects of lycopene from tomato juice on liver of rats with induced hepatic steatosis. J Nutr Biochem, 2013. 24(11): p. 1870-81.
Gao, Q., et al., Atherogenic diets exacerbate colitis in mice deficient in glutathione peroxidase. Inflamm Bowel Dis, 2010. 16(12): p. 2043-54.
Lichtman, A.H., et al., Hyperlipidemia and atherosclerotic lesion development in LDL receptor-deficient mice fed defined semipurified diets with and without cholate. Arterioscler Thromb Vasc Biol, 1999. 19(8): p. 1938-44.
Marcondes, M.C., et al., Effects of chronic mental stress and atherogenic diet on the immune inflammatory environment in mouse aorta. Brain Behav Immun, 2011. 25(8): p. 1649-57.
Nishina, P.M., et al., Effects of dietary fats from animal and plant sources on diet-induced fatty streak lesions in C57BL/6J mice. J Lipid Res, 1993. 34(8): p. 1413-22.
Nishina, P.M., et al., Atherosclerosis and plasma and liver lipids in nine inbred strains of mice. Lipids, 1993. 28(7): p. 599-605.
Yue, P., et al., Enhanced hepatic apoA-I secretion and peripheral efflux of cholesterol and phospholipid in CD36 null mice. PLoS One, 2010. 5(3): p. e9906.
Nishina, P.M., J. Verstuyft, and B. Paigen, Synthetic low and high fat diets for the study of atherosclerosis in the mouse. J Lipid Res, 1990. 31(5): p. 859-69.
*Sodium cholate or cholic acid aid cholesterol and fat absorption and reduce cholesterol disposal via bile acid synthesis. However, if including a cholate source is not desired for your research, diets without cholate are available. See TD.96121 for a purified diet and TD.94059 for a hybrid diet. Contact us for additional options.
Hybrid high fat diets with added cholesterol and cholate source*
Beverly Paigen and colleagues first characterized atherosclerosis development in C57BL/6 mice by feeding a hybrid atherogenic diet. The hybrid diet was created by mixing a natural ingredient mouse diet in a 3:1 ratio with a concentrated purified diet (containing 5% cholesterol and 2% sodium cholate; referred to as Thomas-Hartroft diet). The resulting mixture recreated in TD.88051 /TD.90221 (same formula) contains ~15.8% fat, 1.25% cholesterol, and 0.5% sodium cholate. This group later compared the hybrid atherogenic diet approach to the more modern “western” purified atherogenic diet with added cholesterol and cholate and found that the hybrid atherogenic diet induced more gallstones and liver damage. Hybrid diets contain a variety of unrefined ingredients that may modify lipid metabolism and atherogenesis and do not allow for precise control of ingredients and nutrients for the study of chronic diseases. Although more refined diets have been developed, hybrid atherogenic diets are still popular for inducing mild atherosclerosis and gallstones in wild type mice and rats. Contact us for more information, modifications, or possible control diets.
Examples of hybrid high-fat diets with added cholesterol and cholate source*:
TD.88051 and TD.90221 (same formula) are Teklad product codes for hybrid atherogenic diets
Example of hybrid high-fat diet with added cholesterol (without cholate source):
Induce hypercholesterolemia and mild atherosclerosis (foam cells, fatty streaks) primarily in wild type mice and rats.
Will not promote obesity.
Also used for lithogenic (gallstone) rodent studies.
Key dietary features:
75% rodent breeder diet; 25% purified ingredients
High fat (~15% by weight; 37% kcal from fat)
Saturated fatty acids (SFA >45% of total fatty acids)
Cholesterol (1.25%)
Cholate source (0.5%)*
References:
Nishina, P.M., J. Verstuyft, and B. Paigen, Synthetic low and high fat diets for the study of atherosclerosis in the mouse. J Lipid Res, 1990. 31(5): p. 859-69.
Clee, S.M., et al., Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis. J Lipid Res, 2000. 41(4): p. 521-31.
George, J., et al., Enhanced fatty streak formation in C57BL/6J mice by immunization with heat shock protein-65. Arterioscler Thromb Vasc Biol, 1999. 19(3): p. 505-10.
Miyake, J.H., et al., Transgenic expression of cholesterol-7-alpha-hydroxylase prevents atherosclerosis in C57BL/6J mice. Arterioscler Thromb Vasc Biol, 2002. 22(1): p. 121-6.
Paigen, B., et al., Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis, 1987. 68(3): p. 231-40.
Schreyer, S.A., D.L. Wilson, and R.C. LeBoeuf, C57BL/6 mice fed high fat diets as models for diabetes-accelerated atherosclerosis. Atherosclerosis, 1998. 136(1): p. 17-24.
Vergnes, L., et al., Cholesterol and cholate components of an atherogenic diet induce distinct stages of hepatic inflammatory gene expression. J Biol Chem, 2003. 278(44): p. 42774-84.
*Sodium cholate or cholic acid aid cholesterol and fat absorption and reduce cholesterol disposal via bile acid synthesis. However, if including a cholate source is not desired for your research, diets without cholate are available. See TD.96121 for a purified diet and TD.94059 for a hybrid diet. Contact us for additional options.
Standard diets with added cholesterol
Standard, natural ingredient diets with cholesterol added are fed to induce hypercholesterolemia. Various levels of cholesterol, fat, and/or bile salts can be added to one of the numerous standard rodent diets stocked by Envigo Teklad. For many applications, adding these components to Envigo’s minimal-to-moderate phytoestrogen global rodent diets is recommended. Our minimal phytoestrogen global rodent diets are soybean meal free, limiting the effect of phytoestrogens on your research outcomes. Soybean meal, a common dietary source of phytoestrogens, has been shown to decrease aortic fatty streak development and modify plasma cholesterol, which may reduce the risk of developing atherosclerosis. Limiting dietary soybean meal may reduce confounding variables within your dietary-induced atherosclerosis model. Contact a nutritionist to discuss additional diet options.
Examples of minimal and moderate phytoestrogen rodent diets with added cholesterol:
Induce hypercholesterolemia in genetically-modified and wild type models without promoting obesity.
Key dietary features:
Standard, grain-based rodent diet
Minimal/moderate phytoestrogen diets recommended
Cholesterol (1 – 4%)
References:
Belch, J.J., et al., Longitudinal assessment of endothelial function in the microvasculature of mice in-vivo. Microvasc Res, 2013. 85: p. 86-92.
Hartvigsen, K., et al., A diet-induced hypercholesterolemic murine model to study atherogenesis without obesity and metabolic syndrome. Arterioscler Thromb Vasc Biol, 2007. 27(4): p. 878-85.
Diets for additional animal models of atherosclerosis
Rabbits, hamsters, and swine are common models of atherosclerosis. Contact a nutritionist for information and formula examples. See rabbit, swine and other species for information and formula examples.
For additional phytoestrogen information, see our list of phytoestrogen references.
A few protein adjusted formulas are shown below. Please contact us for additional formulas of this nature or for more information about altering the protein type or content of a diet.
These diet examples are from a series of diets with the following features: casein-based, isocaloric (3.8 kcal/g) and matched for fat (5.5%), calcium (0.7%), and phosphorus (0.54%). There are other diets available from this series of diets, as well as other unique protein adjusted diets.
Casein is the most widely used refined protein source, but it is also possible to use other refined protein sources, such as “vitamin-free” test casein (alcohol extracted), lactalbumin, isolated soy protein, and egg white solids. These particular protein sources are usually used to achieve a specific research objective, rather than for routine use. For instance, vitamin-free test casein is most appropriately used in vitamin deficient diets, and egg white solids is most suitable for zinc or biotin deficient diets.
Adjusted protein diets usually range from “protein-free” (trace) to 60% protein, depending on the research.
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Running an effective research study requires reliable products and processes.
At Envigo, our quality assurance team is an integral part of delivering the consistent research models and services that you expect for your program.
Our curriculum ensures compliance with our policies as well as requirements set by AAALAC, IACUC and the USDA. To maintain our high standards, our quality assurance team is comprised of quality professionals with relevant industry certifications and credentials. In order to support our core value of animal welfare, and to optimize consistent, correct, and reliable research models for you, the provision of quality services within Research Models Services (RMS) is implemented within a framework that is closely aligned with the international standard, ISO 9001:2015.
Our quality assurance services include:
Core SOPs and document lifecycle control
Development of internal quality management systems, such as robust deviation and change management program
Continuous process improvement initiatives
Preventive controls including auditing services
Accurate data analytics through the use of TrackWise®, a leading complaint management system
Through the effective application of a risk-based quality management system and an internal continuous improvement process, we proactively monitor, track and remediate issues as they arise. This strategic method allows us to quickly take action and improve operational performance. Externally, we work with global regulatory authorities to verify that our operations, facilities and processes meet or exceed local and international standards.
With best practices identified and replicated across our global sites, we can offer high-quality research models and services that uphold our stringent quality assurance standards and our brand promise to enable your ongoing success.
Corporate social responsibility (CSR) has always been part of the way we’ve done business — it’s what we do and how we do it.
Our vision is ‘Working together to build a healthier and safer world.’ We work with our customers in the knowledge that the research they conduct, and the products we help them develop, have the potential to enhance life. Our role is to deliver the highest levels of ethical and scientific standards, customer service and compliance.
Our commitment to acting responsibly in achieving this vision is strengthened by our company values:
Doing our best work, together, every day
Caring about each other, our animals and the environment
Being honest and respectful
Always learning, challenging and improving
These values provide guidance and perspective in the way we manage our business, enabling us to act as a responsible company and ensuring that decisions take account of ethical, social and environmental concerns.
This commitment to CSR helps us to serve our customers, operate efficiently and sustainably, gain the trust of our stakeholders, and foster the right environment to further develop our business.
Our CSR is focused on the following areas:
Labour and human rights
Combating bribery and anti-competitiveness
Data protection
Animal welfare
Environment
Compliance and accreditation
At Envigo we are committed to corporate social responsibility.
Envigo is continuously monitoring, preparing and updating its guidance to customers as we approach the key dates of the Article 50 separation of the United Kingdom from the European Union (aka “Brexit”). Envigo established a Brexit task force consisting of senior leadership from key areas of our business to ensure ongoing business continuity for both Envigo and its customers.
This task force continues to meet regularly in order to prepare and implement business process plans and resourcing to anticipate and minimize the impact of Brexit on our business. The following FAQs have been prepared as current guidance and is continually updated as the position between the British Government and the EU develops.
Brexit is a priority for Envigo and if you have any concern, please contact us at brexit@envigo.com.
Will there be tariffs applied to animal costs under WTO?
Laboratory animals currently have no tax added for movement in to the EU and across the EU, this position will remain the same under WTO
Prices for 2021 are being reviewed as normal and will be confirmed in due course.
Will there be changes in documentation needed for movements of animals in or out of the UK?
Import to UK Changes: Envigo’s current understanding is that there will be limited change in terms of documentation required.
DEFRA have now confirmed that no additional vet checks on arrival will be required
Also customers can use the AHPA License for the import into the UK of live rodents or lagomorphs for research. Our Customer Services team are talking to the relevant customers and can advise any new customers as required
Our Customer Services team is working directly with customers to make the necessary changes to Incoterms
Export from UK Changes: Envigo understands that the export documentation will need to be agreed with the EU and may require an additional licence per shipment. This may take an additional time to secure plus an additional vet check may be required prior to shipment. We are working with EU groups to clarify this position and will update customers once a firm position is confirmed.
Documentation: Exact documentation requirements are to be clarified, please contact your customer services representative if you have immediate concerns.
Will there be any other impact on the movement of animals in and out of the UK?
The main impact we currently predict is additional delays in shipments due to:
Export license requests may add time to the process from PO to shipment for small animals being shipped from the UK to the EU. Vet checks might be required at Border Inspection Posts at the airport of arrival.
Additional CITES might be required and thus may add additional time for shipments of animals requiring to travel under CITES from the EU to the UK.
Will there be tariffs on any other goods imported in and out of the UK under WTO?
Under WTO terms the Envigo team have assessed that there will be additional tariffs on certain goods including our Teklad diet shipments into the UK. Additional costs are being assessed and any cost impact to clients will be conveyed to customers via our commercial sales team as soon as possible.
Has Envigo ensured that its supply chain for its Operations are ready for the change on 1st Jan?
Envigo’s Procurement team continues to work with it’s key suppliers in the UK to ensure that supply chains are secure for the post Brexit period. The team are encouraging suppliers to ensure that they have sufficient stock to cover any transition period at the beginning of January.
What will the impact be on the movement of biological products (UK to customer EU and EU to UK)?
We are working with the governmental authorities in the relevant countries together with our international couriers to determine labelling / commercial invoice / payment of VAT / export license & vet check requirements. We will update all parties once further clarity is obtained. We are sure that this will be determined to ensure continuity of these services as we transition to the post Brexit position.
Does Envigo think movement of animals in and out of the UK will have the changes in place ready for 1st Jan?
Envigo recommends that its clients do not request animals deliveries in or out of the UK during the first two weeks of January in order to ensure that all changes at borders and documentation are in place. If there is a requirement for a shipment early in January we would request that you contact your customer services representative as early as possible in December order that the necessary plans can be put in place.
Are there any specific concerns in relation to shipments to Ireland?
The changes in movement of goods from UK to both Northern and Southern Ireland is still unknown – further clarification will be provided when we have more information.
Talent
What proportion of Envigo’s UK employees are EU nationals?
Less than 6% of Envigo’s UK employees are EU nationals. We have worked with all of these employees to ensure they have the relevant rights to live / work in the UK or EU as appropriate
What is Envigo’s expectation of the impact of immigration challenges to staffing your UK-based operation?
This is not expected to have significant impact as Envigo has separate distribution centres in both the UK and EU to enable us to continue to operate under the most favourable trading environment for our customers regardless of trading arrangements between the UK and the EU, or between the UK, EU and the rest of the world. We are committed to recruiting and retaining the best people and to pursue our mission to be the best company to work with and the best company to work for.
Financial
What will be the impact on Envigo’s finances?
Envigo is financially stable and resilient: Though there might be minor changes arising from the Brexit transition, we believe that there will not be any significant adverse impact to the business and we will continue to invest in world-class operations and innovation post Brexit.
Impact of exchange rate movements on costs, profitability and competitive position
Exchange rate movements are an inevitable fact of the business environment and occur because of numerous factors including, inflation, government fiscal policy, real gross domestic product GDP and expectations around future economic performance and the impact of speculative currency investment. In this regard, they are not deemed to be solely a Brexit specific issue. Exchange rate risk is mitigated by Envigo due it being an international business, which has regional operational centres in proximity to the customer base incurring costs in the same currency of sale.
Data Protection/GDPR
What is will be the status of the General Data Protection Regulation (2016/679) (GDPR) after the transition period.
The UK is committed to maintaining the high standards of the GDPR and the government plans to incorporate it via the European Union (Withdrawal) Act 2018 into UK law alongside the Data Protection Act 2018, at the end of the transition period.
What safeguards will be in place for 1. UK to EEA Personal Data flows; 2. EEA to UK Personal Data flows; and, 3. UK sharing data outside the EEA after the transition period?
The UK government has stated that transfers of Personal Data to the EEA will not be restricted and that no additional steps are necessary at this time.
The European Commission is presently deliberating on an adequacy decision under Article 45(3) of the GDPR which would enable the transfer of personal data from EEA states to the UK without requiring any further safeguards. Pending such an adequacy decision or in the absence thereof, Envigo is putting in place approved safeguards in the form of standard contractual clauses.
Rules for sharing data with countries outside the EEA will remain similar.The UK government has confirmed that there will be transitional provisions to recognise existing EU adequacy decisions and EU-approved transfers safeguards.
Other
What Brexit scenario is Envigo planning for?
At this stage Envigo is planning for a “no-deal” scenario and have put the necessary actions in place to manage its business on this basis
Has Envigo undertaken an internal assessment of what impact Brexit will have on customer’s business operations?
Yes, Envigo continues to assess the potential impact of Brexit on both our customers and suppliers. In response to Brexit we have:
Our internal task force is continuously assessing the overall business risks
Developing a range of contingency plans to mitigate the effects
Envigo are taking a leading role and working with various industry associations. ABPI, BIA, EARA, and UK government departments (e.g. DEFRA, Home office, Her Majesty’s Revenue and Customs (HMRC)). At this stage there are still uncertainties on specific issues e.g. CITES and as such there are still risks that we continue to try and mitigate against. As a result, we would recommend that cross border shipment in the first two weeks of January be avoided.
Have you developed a plan to mitigate the Brexit risks you have identified?
Yes, and are already initiating action and contingency plans to address potential impacts on our business based upon our current understanding.
Does Envigo review and adjust plans based on Brexit negotiations and wider external events?
Yes, our internal task force is continuously assessing the overall business risks, to ensure the plans are both relevant and appropriate to the current political situation.
Whom may we contact to follow up on the responses to Brexit mitigation plans?
An e-mail address has been established: brexit@envigo.com. This is available for use to allow any specific follow up questions to be raised that you might have in relation to Envigo’s Brexit mitigation plans.
Glossary
ABPI
Association of British Pharmaceutical Industry
BIA
Bioindustry Association
CLP
Classification, Labelling and Packaging
CITES
Convention on International Trade in Endangered Species of Wild Fauna and Flora (also known as the Washington Convention)
DEFRA
Department for Environment, Food and Rural Affairs
DPB
Data Protection Bill
EARA
European Animal Research Association
EU27
European Union (the 27 European Union countries involved in Brexit negotiations)
The sodium content of natural ingredients such as corn, wheat, and soybean meal is low. Thus, these ingredients can be used to create a base diet that is sodium deficient. To this base diet, various amounts of sodium chloride salt (NaCl) can be added, and other ingredients adjusted slightly to maintain a relatively constant nutrient profile (with the exception of sodium and chloride).
Below are examples from a popular series of adjusted NaCl diets. Contact us for more information.
* When added to natural ingredient diets, these water soluble food dyes offer a slight color tint. More intense color can be achieved at higher inclusion rates.
Ask a nutritionist about additional salt concentrations or color options.
These diets are grain-based, with no animal derived ingredients, and have a background sodium content of approx. 0.01-0.02% and a background chloride content of approx. 0.06-0.07%. The selected nutrient content of the diets are as follows: approximately 19% protein, 5% fat, 3% crude fiber, 0.86% Ca, 0.64% P, 0.72% K, and 0.15% Mg.
NaCl adjusted diets are often fed to dahl salt-sensitive/resistant (rapp) inbred rats. These rats are maintained on Teklad traditional diet 7034 (0.12% NaCl) within maximum security production facilities.
For additional formulas of this nature, or for a purified sodium adjusted diet, please email us at askanutritionist@envigo.com.
Not all products are stocked locally; extended lead time and additional fees may apply. Many diets are available in certified format designated by a “C” following the product code. When diets are certified a representative sample is tested for a panel of contaminants. If not stocked as certified, certification can be made available upon request. Minimum order size and additional charges may apply.
There are numerous possibilities in adjusting both the level and source of fat in a diet. If your primary interest is inducing atherosclerosis or obesity, additional information can be found on our Teklad atherogenic and diet induced obesity (DIO) diet pages. Depending on your research goals and level of desired fat supplementation, fats can be added to a standard natural ingredient diet or a purified diet.
Purified ingredients are refined to the point of chemical simplicity and allow for extreme fat levels such as no fat diet TD.03314 or very high fat ketogenic diet TD.96355 . Unless adjustments are made to the level of fiber, diets with high fat levels will have a greater caloric density since fat contains 9 kcal/g versus 4 kcal/g for carbohydrate or protein. Animals are good at regulating caloric intake, therefore it is common to adjust other nutrients (vitamins, minerals, protein) relative to energy content to account for differences in feed intake.
Specific fats can be utilized as in this essential fatty acid deficient diet TD.84224 or to provide high levels of omega-3 polyunsaturated fat from flaxseed or fish oil. Normally, 1-2% fat from plant sources like corn or soybean oil will supply sufficient levels of essential fatty acids. Additional fat provides energy and can influence palatability due to effects on taste and texture of the diet.
Mixtures of fats can be used to mimic a Western or Mediterranean diet fatty acid profile. Contact us for a table comparing the fatty acid composition of several stocked fat sources (solid fats, oils).
We also commonly work with customer supplied oils and purified fatty acids such as DHA and EPA. If you prefer to mix fat sources in your lab, ask about a basal mix. Basal mixes are supplied in powder form and often allow you to use one diet mix for creating several different diets.
If fat stability is a concern, contact a nutritionist to discuss options for diet drying, vacuum packaging, and synthetic antioxidant supplementation.
You may want to add some specific ingredients in your own facility. In that case, Envigo provides basal mixes that are, by design, a starting point for additional inclusions. When you choose a basal mix diet, you simply add any ingredient(s) in a specific proportion that your require. The nutrient levels in our basal mix are adjusted to account for the dilution of the added ingredient(s), so that the final complete diet contains the desired nutrient levels.
