A simple action reduces high fat diet intake and obesity in mice

Abstract

Diets that are high in fat cause over-eating and weight gain in multiple species of animals, suggesting that high dietary fat is sufficient to cause obesity. However, high-fat diets are typically provided freely to animals in obesity experiments, so it remains unclear if high-fat diets would still cause obesity if they required more effort to obtain. We hypothesized that unrestricted and easy access is necessary for high-fat diet induced over-eating, and the corollary that requiring mice to perform small amounts of work to obtain high-fat diet would reduce high-fat diet intake and associated weight gain. To test this hypothesis, we developed a novel home-cage based feeding device that either provided high-fat diet freely, or after mice poked their noses into a port one time - a simple action that is easy for them to do. We tested the effect of this intervention for six weeks, with mice receiving all daily calories from high-fat diet, modifying only how they accessed it. Requiring mice to nose-poke to access high-fat diet reduced intake and nearly completely prevented the development of obesity. In follow up experiments, we observed a similar phenomenon in mice responding for low-fat grain-based pellets that do not induce obesity, suggesting a general mechanism whereby animals engage with and consume more food when it is freely available vs. when it requires a simple action to obtain. We conclude that unrestricted access to food promotes overeating, and that a simple action such as a nose-poke can reduce over-eating and weight gain in mice. This may have implications for why over-eating and obesity are common in modern food environments, which are often characterized by easy access to low-cost unhealthy foods.

Figure 1:. Design of the Tumble Feeder.

A. 3D design of the Tumble Feeder. B. Back view of the assembled Tumble Feeder with relevant part labels. C. Front view of the Tumble Feeder in both open- and closed positions. D. Photographs of Tumble Feeder in a mouse home-cage. E. Average daily weight of mice during Free vs. FR1 tasks for laboratory chow (n=8). F. Number of active and inactive pokes per day in the Free and FR1 modes (n=8 mice, 5 days in each phase).

Figure 2:. Mice take less high-fat diet and gain less weight on FR1 vs. Free access.

A. Average weight of mice across Free and FR1 phases for chow and high-fat diet (n=12 male mice). B. Weight gain in each phase. C. Food taken in each phase. D-F. same plot format as A-C, but for 8 female mice. ** denotes p<0.001 * denotes p<0.05.

Figure 3:. FR1 access to high-fat diet prevents, but does not reverse, obesity.

A. Weight of mice on FR1 for high fat diet for 6 weeks, followed by Free access for six weeks (n=7 male mice). Dashed line is predicted growth curve of age-matched C57Bl6 mice from Jackson labs. B. Average weight at the end of the FR1 (week 6) vs. Free periods (week 12). C. Average weight of mice on Free access for high fat diet for 6 weeks, followed by FR1 access for six weeks (n=7 male mice). D. Average weight at the end of the Free (week 6) vs. FR1 access period (week 12). ** denotes p<0.001 * denotes p<0.05.

Figure 4:. Mice take more grain pellets during Free vs. FR1 access.

A. Locations of labs from which FED3 data was collected (n=10 study locations). B. Average pellet count for mice on the Free vs. FR1 task across study locations (n=105 mice). C. Histogram of inter-pellet intervals with a meal cutoff line. (Inset) Average inter-pellet interval for free vs FR1 task. D. Histogram of meal sizes for Free vs FR1 tasks (n=105). (Insets) Average count and size of meals in each task. E. Circadian plot of average pellets per hour over 24 hours for Free vs FR1 tasks. F. Pellets taken by males (n=72) and females (n=33) in Free vs FR1 tasks. ** denotes p<0.001 * denotes p<0.05.