Why Do Mice Overeat High-Fat Diets? How High-Fat Diet Alters the Regulation of Daily Caloric Intake in Mice

Abstract

Objective: Ad libitum high-fat diets (HFDs) spontaneously increase caloric intake in rodents, which correlates positively with weight gain. However, it remains unclear why rodents overeat HFDs. This paper investigated how changing the proportion of diet that came from HFDs might alter daily caloric intake in mice.

Methods: Mice were given 25%, 50%, or 90% of their daily caloric need from an HFD, along with ad libitum access to a low-fat rodent chow diet. Food intake was measured daily to determine how these HFD supplements impacted total daily caloric intake. Follow-up experiments addressed the timing of HFD feeding.

Results: HFD supplements did not alter total caloric intake or body weight. In a follow-up experiment, mice consumed approximately 50% of their daily caloric need from an HFD in 30 minutes during the light cycle, a time when mice do not normally consume food.

Conclusions: An HFD did not disrupt regulation of total daily caloric intake, even when up to 90% of total calories came from the HFD. However, HFDs increased daily caloric intake when provided ad libitum and were readily consumed by mice outside of their normal feeding cycle. Ad libitum HFDs appear to induce overconsumption beyond the mechanisms that regulate daily caloric intake.

Figure 1. Food intake, weights and energy expenditure all positively correlate

(A) weights plotted with food intake, (B) weights plotted with daily energy expenditure, (C) weights plotted with average speed in an open field test, and (D) daily energy expenditure plotted with food intake per mouse.

Figure 2. High fat diet leads to overeating

Mice were fed diets with varying percentages of fat derived from either lard (A) or vegetable shortening (B) for 3 days. Average daily kcal consumed per mouse per diet is plotted with circles for individual mice. * indicates p<0.05 on Sidak’s multiple comparison test.

Figure 3. Animals fed limited HFD supplements do not overeat

(A) Schematic of the experiment: mice were given ad libitum access to chow while a subgroup was also given an increasingly higher amount of HFD supplements. (B) Average total kcal consumed per day for each week of varying HFD supplements. (C) Average kcal consumed per condition (bars) and per mouse (circles) for each supplement phase. (D) Weekly average weights per group for the duration of the experiment. * indicates p<0.05 on Sidak’s multiple comparison test.

Figure 4. Animals fed ad libitum HFD overeat

(A) Average total kcal consumed per day for a week of mice fed ad libitum HFD or chow. (B) Average kcal consumed per condition (bars) and per mouse (circles). (C) Weekly average weights per group. **** for p<0.0001.

Figure 5. Animals fed HFD in multiple dispenses do not overeat, but do binge on HFD

(A) Schematic of the experiment: mice were first given a HFD supplement with 50% of their daily caloric intake provided at a single time daily for 8 days or mice were then given the same total amount of HFD, but dispensed gradually every 4 hours for a total of 6 dispenses. (B) 3D illustration of the HFD dispenser and (C) position of dispenser in a home cage. (D) Average total kcal consumed per day for a week with 50% of the mice’s caloric need provided by a HFD supplement given at one time (day 1-8) then dispensed gradually every 4 hours (day 9-16). (E) Average kcal consumed per HFD dispensing count. (F) Total amount (kcal) of HFD or chow consumed by mice in 30 minutes during the light cycle. * for p<0.05 and **** for p< 0.0001.