Understanding the effect of high-fat rodent diets on obesity phenotypes

Studying obesity, diabetes, insulin resistance, or other metabolic syndromes requires feeding rodents purified, high-fat diets, but at what age should a high-fat diet be introduced to a model? Which type of high-fat rodent diet can enhance development of obesity phenotypes? To answer these important questions, researchers at Inotiv ran a study with 144 male C57BL/6 mice to understand the differences in diet response.

The experiment compared both the age of starting the high-fat diets, as well as the differences between types of high-fat diets. With all models beginning on a fixed formula vegetarian grain-based diet, the experimental groups were formed and given one of three diets:

• 17F7S (TD.08810, now TD.120455): A low glycemic control diet with resistant starch to more closely resemble digestion of a natural ingredient standard diet, which served as the control.
• 45F30S (TD.08811): A so-called “Western Diet” with ~45% of kcal from fat using primarily milkfat and with ~30% kcal from sucrose.
• 60F10S (TD.06414): A high-fat rodent diet with an industry standard formulation with~60% of kcals from fat using primarily lard.

Measuring diet-induced differences
Introducing one of the diets at either 3 weeks, 6 weeks, or 9 weeks of age, the researchers monitored body weight and food disappearance once weekly across the nine groups of mice, with 15-16 mice per group. Additional phenotyping was assessed through:

• Body Composition by DEXA at 9, 15, and 19 weeks of age
• Oral Glucose Tolerance Test, 2 g/kg, at 17 weeks of age

A concurrent cohort of mice (20 per group) started on diets at 3 weeks of age were shipped to a collaborator and evaluated at 11 and 19 weeks of age for:

• Body Composition with Nuclear Magnetic Resonance (NMR)
• Serum Triglycerides, Cholesterol, and Liver Triglycerides
• Serum Insulin and Leptin levels

Comparing the weights
As expected, mice consuming the high-fat rodent diet starting at 3 weeks of age were significantly heavier than their controls after 3-4 weeks. However, mice introduced to the high-fat diet at 6 and 9 weeks of age quickly attained similar weight compared to mice introduced to the diet at 3 weeks of age. One exception was noted in the group receiving 60F10S (high fat lard diet) at 9 weeks of age. This group failed to catch up to the body weight of the other high-fat diet groups by 19 weeks.

Analyzing the variances
Even with the notable difference of body weight in one cohort, the researchers concluded that both high-fat rodent diet patterns produced similar obesity phenotypes. Regardless of when the high-fat diet was started, or if consuming 45F30S or 60F10S, the C57BL/6N mice showed:

• Similar percent body fat that was nearly double that of the control
• Impaired glucose tolerance

The concurrent cohorts that started in high-fat diets at 3 weeks of age showed:
• High liver triglyceride levels
• Histological liver changes consistent with hepatocellular lipid accumulation

Despite similar body fat percentages and developing hyperinsulinemia and hyperleptinemia, mice fed 60F10S had 2-fold higher serum leptin at 19-20 weeks of age as compared to mice fed 45F30S. This is one interesting finding that may guide decision making in studies that need to account for serum leptin levels.

If you’d like to learn more about high-fat rodent diets, diet induced obesity or discuss your upcoming study needs, please send an email to Teklad nutritionists at askanutrutionist@inotivco.com. You can also download the study poster.