34 Investigating the Impact of a Ketogenic Diet in Mice: Effects on Food Intake and Body Composition

A ketogenic diet (KD) is a very high-fat, low-carbohydrate diet that has been used to treat epilepsy since the discovery of its benefits in 1921 by Dr. Russel Wilder [1]. The mechanisms for why it works are unclear. The ketogenic diet experienced a surge in interest in controlling weight and body composition starting in the 1960s and regaining popularity in the 2000s. There are two reasons for this resurgence: 1) A KD is believed to decrease insulin and glucose levels promoting the burning of fat and adipose stores in the body and 2) it may increase satiety levels and decrease food intake, leading to a reduction in body weight. It is well known that a 60% fat diet induces obesity in mice, but studies have found that weight gain declines with an increasing amount of fat in the diet [2]. However, it is unclear whether differences in body weight on a KD are due to reduced food intake or increased fat-burning. Therefore this study aimed to elucidate whether a KD affects food intake, body weight, and body composition.

Methods

We used 90 male C57BL/6J mice (n=15-20/ group), aged 14 weeks at the start of the study. We compared the effects of a ketogenic diet (:10% kcal from protein, 0.1% kcal from carb, 89.9% kcal from fat) to four different diets, including a high-fat diet (: 20% kcal from protein, 20% kcal from carb, 60% kcal from fat), a high-fat low-carbohydrate diet (: 40% kcal from protein, 60% kcal from fat), a low-fat control diet (:20% kcal from protein, 70% kcal from carb, 10% kcal from fat), and a low-fat diet in which the % protein content was matched to the ketogenic diet (protein control:10% kcal from protein, 80% kcal from carb, 10% kcal from fat). Body weight and food intake were monitored weekly, while body composition was measured every 4 weeks for a total of 8 weeks.

Results

We confirmed that ketogenic diet-fed mice were in ketosis as measured by significantly more β-hydroxybutyrate compared to all other diets. There were no statistically significant differences in food intake between mice fed a ketogenic diet and those fed control, protein control, or high-fat low-carbohydrate diets. There was no statistically significant increase in body weight in the mice fed the ketogenic diet compared to the low-fat diets’ whereas mice on 60% high-fat diet gained weight. Yet, the mice on a ketogenic diet had a similar increase in fat mass but no change in lean mass comparable to high-fat diet-fed mice throughout the experiment.

Conclusions

Results suggest that the ketogenic diet may prevent weight gain when compared to the high-fat diet. However, the ketogenic diet affects body composition as evidenced by an increase in body fat over the 8 weeks when compared to high-fat low-carbohydrate, protein control, and control diets. These results were not expected as there was no change in the food intake yet an increase in fat percentage with body weight remaining consistent. In future studies, the type of fat, protein, or proportion of carbohydrates could be altered to see whether that affects the results. Additionally, investigations into other strains of mice or female mice could be added to the research to determine whether these effects that we have observed hold true in different sexes and strains. Analyzing the cholesterol, triglycerides, activity, and energy expenditure could also help determine why the ketogenic diet suppresses weight gain as compared to a 60% HFD. This research could be used to better educate people wanting to go on this diet to make the best decision for themselves. It can also serve as a baseline for comparing the effects of a KD on weight in clinical studies.