Tight Regulation of Energy Intake and Expenditure Across a Temperature Spectrum is Disrupted at Thermoneutrality
Authors: Ono-Moore Kikumi D. , Rutkowsky Jennifer M. , Pearson Nicole A. , Grobe Justin L. , Tolentino Todd , Ramsey Jon J. , Lloyd K.C. Kent , Adams Sean H. 
Published: April 2020

Energy balance is exquisitely regulated by peripheral and central hormones, brain behavioral centers, and neuronal networks. Under homeostatic conditions, energy intake (EI) is well matched to energy expenditure (EE), presumably via hypothalamic cross‐talk among: peripheral somatosensory afferents, sympathetic nervous system regulators, and feeding sites. The paradigm of closely matched energy balance is not evident during every life stage (e.g., normal growth and development, pregnancy) or in certain diseases (obesity). This highlights a disconnect between systems controlling EI from those controlling EE. We hypothesized that high fat diet (HFD)‐induced obesity (DIO) in mice would disrupt the normal energy intake‐expenditure relationship across a spectrum of temperatures. C57BL/6N male mice were fed a HFD (45% of energy) for ~9 wk, and were split into quartiles (n=8 ea) based on body weight (BWT) to study DIO resistant (Q1) vs. susceptible (Q4) mice compared to low fat (LF) controls. To assess EI and EE during a temperature challenge, 3 d/temperature food intake and indirect calorimetry (IC) measures took place at 10, 20, and 30°C. Despite differences in DIO susceptibility, BWT covariate‐adjusted EE responses to temperature did not differ between Q1 and Q4 mice. As expected, EE increased in all groups transitioning from the TNZ toward 20 and 10°C. EI matched EE at both 20 and 10°C, indicating tight co‐regulation at these temperatures. EI displayed a different pattern at 30°C: calorie consumption was not reduced compared to 20°C, resulting in positive energy balance and BWT gain. Respiratory exchange ratio percent relative cumulative frequency (PRCF) curves at 10 and 20°C indicated more fat combustion in HFD mice vs. LF controls, regardless of DIO status. 30°C led to a rightward shift in the PRCF in all mice, indicative of increased de novo lipogenesis and energy storage.Conclusions1) Countering our hypothesis, obesity did not significantly alter patterns of EI or EE at different temperatures. This suggests that temperature‐sensitive systems that coordinate energy balance in this DIO model remain largely intact. 2) During the fattening period before temperature challenge, hyperphagia only accounted for part of BWT gain in DIO susceptible mice, yet EE calculated from IC did not differ in DIO susceptible‐ vs. resistant mice. Thus, common assumptions related to EE calculation from IC might not be accurate under DIO conditions. 3) Tight co‐regulation of EE and EI was disrupted in mice within the TNZ, leading to hyperphagia and weight gain. The mechanisms behind this EE/EI decoupling remain to be identified. The current experimental paradigm provides a unique system to identify novel temperature‐sensitive factors in the hypothalamic, somatosensory, and sympathetic systems.Support or Funding InformationFunded by USDA‐ARS Project 6026‐51000‐010‐05S, AR Children’s Research Institute, and AR Biosciences Institute. Support in part by NIH grant U24‐DK092993.