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Clinical Research

Physiological and molecular mechanisms of cold-induced improvements in glucose homeostasis in humans beyond brown adipose tissue

International Journal of Obesity volume 47, pages 338–347 (2023)Cite this article

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Abstract

Exposure to low ambient temperatures has previously been demonstrated to markedly improve glucose homeostasis in both rodents and humans. Although the brown adipose tissue is key in mediating these beneficial effects in rodents, its contribution appears more limited in humans. Hence, the exact tissues and underlying mechanisms that mediate cold-induced improvements in glucose homeostasis in humans remain to be fully established. In this review, we evaluated the response of the main organs involved in glucose metabolism (i.e. pancreas, liver, (white) adipose tissue, and skeletal muscle) to cold exposure and discuss their potential contribution to cold-induced improvements in glucose homeostasis in humans. We here show that cold exposure has widespread effects on metabolic organs involved in glucose regulation. Nevertheless, cold-induced improvements in glucose homeostasis appear primarily mediated via adaptations within the skeletal muscle and (presumably) white adipose tissue. Since the underlying mechanisms remain elusive, future studies should be aimed at pinpointing the exact physiological and molecular mechanisms involved in humans. Nonetheless, cold exposure holds great promise as a novel, additive lifestyle approach to improve glucose homeostasis in insulin resistant individuals.

Parts of this graphical abstract were created using (modified) images from Servier Medical Art, licensed under the Creative Commons Attribution 3.0 Unported License. TG = thermogenesis, TAG = triacylglycerol, FFA = free fatty acid, SLN = sarcolipin, UCP3 = uncoupling protein 3, β2-AR = beta-2 adrenergic receptor, SNS = sympathetic nervous system.

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Fig. 1: Schematic representation of uncoupling protein 1 (UCP1)-dependent and independent thermogenic mechanisms.

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Data sharing not applicable to this article as no datasets were generated or analyzed for the present review.

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SvB is supported by a grant from the Nutrim NWO graduate program.

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  1. Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands

    Sten van Beek, Dzhansel Hashim & Joris Hoeks

  2. Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden

    Tore Bengtsson

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SvB and JH conceived the idea and designed the review. SvB performed the literature search and drafted the manuscript. TB and DH contributed to the further development of the review. All authors revised the manuscript and gave approval for the final version to be published.

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Correspondence to Joris Hoeks.

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van Beek, S., Hashim, D., Bengtsson, T. et al. Physiological and molecular mechanisms of cold-induced improvements in glucose homeostasis in humans beyond brown adipose tissue. Int J Obes 47, 338–347 (2023). https://doi.org/10.1038/s41366-023-01270-z

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