Adaptation of fuel selection to acute decrease in voluntary energy expenditure is governed by dietary macronutrient composition in mice

Abstract

In humans, exercise-induced thermogenesis is a markedly variable component of total energy expenditure, which had been acutely affected worldwide by COVID-19 pandemic-related lockdowns. We hypothesized that dietary macronutrient composition may affect metabolic adaptation/fuel selection in response to an acute decrease in voluntary activity. Using mice fed short-term high-fat diet (HFD) compared to low-fat diet (LFD)-fed mice, we evaluated whole-body fuel utilization by metabolic cages before and 3 days after omitting a voluntary running wheel in the cage. Short-term (24-48 h) HFD was sufficient to increase energy intake, fat oxidation, and decrease carbohydrate oxidation. Running wheel omission did not change energy intake, but resulted in a significant 50% decrease in total activity and a ~20% in energy expenditure in the active phase (night-time), compared to the period with wheel, irrespective of the dietary composition, resulting in significant weight gain. Yet, while in LFD wheel omission significantly decreased active phase fat oxidation, thereby trending to increase respiratory exchange ratio (RER), in HFD it diminished active phase carbohydrate oxidation. In conclusion, acute decrease in voluntary activity resulted in positive energy balance in mice on both diets, and decreased oxidation of the minor energy (macronutrient) fuel source, demonstrating that dietary macronutrient composition determines fuel utilization choices under conditions of acute changes in energetic demand.

Keywords: COVID-19; energy expenditure; high-fat diet; metabolic cages; running wheel.

FIGURE 1

Acute HFD induces a shift in whole‐body fuel utilization. (a) Scheme of study protocol. (b,c) Energy intake and (d,e) Energy expenditure of LFD and HFD mice during active (night) and inactive (day) phases. (b and d) Are hourly averages of energy intake/energy expenditure in each 4‐h interval, and (c and d) are hourly averages of energy intake/energy expenditure per 12 h of active/inactive phases. (f) Hourly average RER of LFD and HFD mice during 12 h of active/inactive phases. Hourly averages of carbohydrate (g) and fatty acid (h) oxidation every 4 h in LFD and HFD mice. Data represent the mean ± SEM from eight mice per group. */**p < 0.05/0.01 within the dietary groups, bar + */**p < 0.05/0.01 between the dietary groups

FIGURE 2

Effect of running wheel omission on voluntary and total activity. Cumulative wheel activity in active (gray bar) and inactive (white bar) phases in LFD (a) and HFD (b) mice. (c,d) Mean hourly activity every 4 h period in LFD and HFD mice, respectively, before and after running wheel omission from the cage. (e,f) Mean hourly activity per 12 h day phase in LFD and HFD mice, respectively, with (full black dots) or without (empty white dots) presence of the wheel. Data represent the mean ± SEM from 4–8 mice per group at each time point. */**p < 0.05/0.01 within the dietary groups, bar + */**p < 0.05/0.01 between the dietary groups

FIGURE 3

Effect of running wheel omission on energy intake and energy expenditure during the active day phase. Hourly average of energy intake (a) and energy expenditure (b) in the active phase (night) in LFD and HFD mice with (black circles) or without (white circles) the presence of running‐ wheel. (c) Three‐day change in body weight with (black circles) or without (white circles) the presence of running wheel. Data represent the mean ± SEM from eight mice per group. */**p < 0.05/0.01 within the dietary groups, bar + */**p < 0.05/0.01 between the dietary groups

FIGURE 4

Effect of acute decrease in voluntary activity on fuel utilization in LFD and HFD mice. Hourly average RER (a), fatty acid (b), and carbohydrate (c) oxidation during active phase (night) in LFD and HFD mice with (black circles) or without (white circles) the presence of running wheel. Data represent the mean ± SEM from eight mice per group. */**p < 0.05/0.01 within the dietary groups, bar + */**p < 0.05/0.01 between the dietary groups