Characterizing the Effects of High Fat and High Carbohydrate Diets on Feeding Behavior and Energy Expenditure in Mice

Benjamin Linden; Hussein Herz; Yi Chu; Mohamad Mokadem

doi:10.1096/fasebj.2022.36.S1.R5818

We sought to characterize how different compositions of the diet can alter feeding behavior and energy expenditure in mice, ultimately driven by changes in sympathetic activation and thermogenesis. Mice on a high fat diet (HFD) will consume more calories/day compared to high carbohydrate diet (HCD) and standard chow fed mice. Mice on HFD will have decreased expression of UCP1 in both brown and white adipose tissue. There will be decreased expression for several lipolytic enzymes in the white adipose of HFD mice. A total of 21 mice were divided into three ad libitum fed diet groups: HFD, HCD, and standard chow. Each group was fed their respective diet for 7 weeks. Changes in weight and percent body fat were recorded by NMR. At week 5, glucose tolerance tests were performed on all mice. Both a 24-hour heat production and respiratory exchange ratio were collected on each group using a metabolic cage system. Mice were sacrificed at the conclusion of week 7 and organs were collected for molecular analysis. We show that mice on both ad libitum HFD and HCD consume significantly more calories/day when compared to standard chow. Both HFD and HCD fed mice have a significantly increased body weight and percent body fat when compared to standard chow; however, the HFD mice had a far greater increase in weight compared to HCD fed mice despite no difference in calorie consumption. Mice on a HFD had a lower 24-hour average heat production per body mass when compared to standard chow and HCD mice and a significantly impaired glucose tolerance test. Furthermore, UCP1 mRNA expression is significantly elevated in brown adipose tissue (BAT) of HCD mice compared to that of HFD and standard chow mice. There were no differences in UCP1 expression in subcutaneous or visceral white adipose tissue (WAT) among all groups. There were also no differences in tyrosine hydroxylase (TH) expression in BAT between all mice. Three markers of lipolysis were decreased in visceral WAT of HFD mice compared to HCD and standard chow counterparts. Mice consumed significantly more calories when fed a HFD or HCD. These mice gain significantly more weight compared to chow with HFD mice gaining weight far more than the HCD group. This major difference in weight gain despite no significant difference in calorie consumption between HFD and HCD suggests differences may be determined by energy expenditure. This evidence is further supported by the fact that HFD fed mice had a significantly lower daily heat production compared to HCD and standard chow mice. We also show that HCD increases thermogenesis in mouse BAT which may be protective against weight gain. Finally, lipolysis signaling seems to be impaired in HFD mice, but no data supports that this is due to differences in sympathetic activation. Further work will include analyzing the same tissues in isocaloric, restricted diet fed mice.

Characterizing the Effects of High Fat and High Carbohydrate Diets on Feeding Behavior and Energy Expenditure in Mice

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