Coupling of energy intake and energy expenditure across a temperature spectrum: Impact of diet-induced obesity in mice

Authors: ONO-MOORE, KIKUMI - Arkansas Children'S Nutrition Research Center (ACNC); RUTKOWSKY, JENNIFER - University Of California, Davis; PEARSON, NICOLE - University Of Iowa; WILLIAMS, D. KEITH - Arkansas Children'S Nutrition Research Center (ACNC); GROBE, JUSTIN - Medical College Of Wisconsin; TOLENTINO, TODD - University Of California, Davis; KENT LLOYD, K.C. - University Of California, Davis; Ferruzzi, Mario

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/19/2020
Publication Date: 7/21/2020
Citation: Ono-Moore, K., Rutkowsky, J.M., Pearson, N.A., Williams, D., Grobe, J.L., Tolentino, T., Kent Lloyd, K., Adams, S.H. 2020. Coupling of energy intake and energy expenditure across a temperature spectrum: Impact of diet-induced obesity in mice. American Journal of Physiology - Endocrinology and Metabolism. 319:E472-E484. https://doi.org/10.1152/ajpendo.00041.2020.
DOI: https://doi.org/10.1152/ajpendo.00041.2020

Interpretive Summary: Weight regulation is important to health and prevention of obesity, yet the detailed mechanisms that balance food intake (energy intake [EI]) to energy expenditure ([EE]: metabolic rate, calorie burning) are not fully understood. New models are needed to unmask which of the body's brain and non-brain systems participate in the crosstalk between energy intake and energy expenditure. The somatosensory (nerves that sense temperature), sympathetic (nerves that can trigger more active metabolism), and hypothalamic (nerves in the brain that coordinate and regulate metabolism) systems are thought to be abnormal in obesity. Since these systems contribute to integrative regulation of EE and EI in response to ambient temperature (Ta) changes, it was hypothesized that diet-induced obesity (DIO) in mice fed a high fat diet disrupts Ta-associated EE-EI coupling. C57BL/6N male mice were fed a high fat diet (HFD, 45% kcal) or low fat diet (LFD, 10% kcal) for ~9.5 wk; HFD mice were then split into body weight (BWT) quartiles (n=8 ea.) to study DIO-resistant (Q1) vs. -susceptible (Q4) mice. EI and indirect calorimetry (measurement of oxygen consumption and carbon dioxide production in the breath) were measured over 3 days each at 10 deg C, 20 deg C, and 30 deg C. Responses did not differ between LFD, Q1 and Q4: EI and EE increased rapidly when transitioning toward cooler temperatures of 20 deg C and 10 deg C in order to maintain body temperature. In all groups, EI at a warmer 30 deg C was not reduced despite lower EE, resulting in EE/EI imbalance and weight gain in all groups. (1) DIO-type obesity did not impair Ta-dependent acute EI/EE coupling, and Ta-sensitive systems that coordinate energy balance remained intact; (2) Rapid coupling of EI/EE at cooler temperatures is an important adaptation to maintain energy stores and defend body temperature, and less critical at warmer temperatures when body temperature is close to environmental temperature. The experimental model provides a new platform to study the biological mechanisms that drive EI/EE coupling and energy balance regulation. This will ultimately enable science-based interventions and strategies to thwart obesity and to help maintain a healthy body weight.

Technical Abstract: Obesity and its metabolic sequelae are implicated in dysfunction of the somatosensory, sympathetic, and hypothalamic systems. Since these systems contribute to integrative regulation of energy expenditure (EE) and energy intake (EI) in response to ambient temperature (Ta) changes, we hypothesized that diet-induced obesity (DIO) disrupts Ta-associated EE-EI coupling. C57BL/6N male mice were fed a high fat diet (HFD, 45% kcal) or low fat diet (LFD, 10% kcal) for ~9.5 wk; HFD mice were then split into body weight (BWT) quartiles (n=8 ea.) to study DIO-resistant (Q1) vs. -susceptible (Q4) mice. EI and indirect calorimetry (IC) were measured over 3 d each at 10 deg C, 20 deg C, and 30 deg C. Responses did not differ between LFD, Q1 and Q4: EI and BWT-adjusted EE increased rapidly when transitioning toward 20 deg C and 10 deg C. In all groups, EI at 30 deg C was not reduced despite lower EE, resulting in positive energy balance and respiratory exchange ratios consistent with increased de novo lipogenesis and relative hyperphagia. Conclusions: (1) DIO did not impair Ta-dependent acute EI/EE coupling, and Ta15 sensitive systems that coordinate energy balance remained intact; (2) Rapid coupling of EI/EE at cooler temperatures is an important adaptation to maintain energy stores and defend body temperature, and less critical at thermoneutrality; (3) Secondary, post hoc analyses indicated that digestible EI plus IC-calculated EE could not explain obesity susceptibility, leading to speculation that standard IC assumptions are not always valid in DIO. The experimental paradigm provides a platform to query the hypothalamic, somatosensory, and sympathetic mechanisms that drive Ta-associated EI/EE coupling.