Intermittent cold exposure improves glucose homeostasis despite exacerbating diet‐induced obesity in mice housed at thermoneutrality

Autor: Hesham Shamshoum, Hana A. Dibe, Jibran Y. Khokhar, Greg L. McKie, David C. Wright, Hayley H. A. Thorpe, Christine A. Doucette, Kristin Hunt
Rok vydání: 2021
Předmět:
Zdroj: The Journal of Physiology. 600:829-845
ISSN: 1469-7793
0022-3751
Popis: Key points Ambient cold exposure is often regarded as a promising anti-obesity treatment in mice. However, most preclinical studies aimed at treating obesity via cold-induced thermogenesis have been confounded by sub-thermoneutral housing temperatures. Therefore, the ability of ambient cold to combat diet-induced obesity in mice housed under humanized thermoneutral conditions is currently unknown. Moreover, mammals such as mice are rarely exposed to chronic ambient cold without reprieve, yet mice are often subjected to experimental conditions of chronic rather than intermittent cold exposure (ICE), despite ICE being more physiologically relevant. Having addressed these issues herein, we provide novel evidence that thermoneutral housing uncouples the effects of ICE on glucose and energy homeostasis suggesting that ICE, despite improving glucose tolerance, is not an effective obesity treatment when mice are housed under humanized thermoneutral conditions. Abstract This study examined whether a physiologically relevant model of ambient cold exposure, intermittent cold exposure (ICE), could ameliorate the metabolic impairments of diet-induced obesity in male and female mice housed under humanized thermoneutral conditions. Male and female C57BL/6J mice housed at thermoneutrality (29 °C) were fed a low-fat diet (LFD) or high-fat diet (HFD) for 6 weeks before being weight matched into groups that remained unperturbed (CTRL) or underwent ICE for four weeks (4 °C for 60 min/day; 5 days/week) while being maintained on their respective diets. ICE induced rapid and persistent hyperphagia exacerbating rather than attenuating HFD-induced obesity over time. These ICE-induced increases in adiposity were found to be energy intake dependent via pair-feeding. Despite exacerbating HFD-induced obesity, ICE improved glucose tolerance, independent of diet, in a sex-specific manner. The effects of ICE on glucose tolerance were not attributed to improvements in whole-body insulin tolerance, tissue specific insulin action, nor to differences in markers of hepatic insulin clearance or pancreatic beta cell proliferation. Instead, ICE increased serum concentrations of insulin and C-peptide in response to glucose, suggesting that ICE may improve glucose tolerance by potentiating pancreatic glucose-stimulated insulin secretion. These data suggest that ICE, despite improving glucose tolerance, is not an effective obesity treatment in mice housed under humanized conditions. Greg L. McKie is a third year PhD Candidate in the Human Health and Nutritional Sciences Department at the University of Guelph, where he works under the supervision of Dr. David C. Wright. Greg's dissertation focuses on the effects of environmental perturbations, such as aerobic exercise and ambient cold exposure, on adipose tissue metabolism, specifically as it relates to promoting non-shivering thermogenesis under translationally relevant thermoneutral conditions. This article is a follow up to Greg's first PhD study, also published in The Journal of Physiology, which demonstrated that housing temperature affects the acute and chronic metabolic adaptations to aerobic exercise in mice. This article is protected by copyright. All rights reserved.
Databáze: OpenAIRE
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