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An unexpected role for bile acid synthesis in adaptation to low temperature

Nature Medicine volume 23, pages 800–802 (2017)Cite this article

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Enhanced conversion of dietary cholesterol to bile acids through the alternative pathway leads to cold-associated, metabolically beneficial changes in the intestinal microbiome and to elevated bile acid levels that contribute to adaptive thermogenesis.

The induction of thermogenesis is a major mechanism for the maintenance of mammalian body temperature in a cold environment. It is an energy-consuming process that occurs particularly in brown adipose tissue (BAT) through activation of the mitochondrial uncoupling protein 1 (UCP1). Exposure to cold activates BAT and also promotes the appearance of so-called brown-like or beige adipocytes in white adipose tissues, with features similar to those of BAT. The role of BAT in maintaining energy homeostasis has drawn growing interest because it is now recognized that adult humans have physiologically relevant amounts of this heat-generating tissue, in contrast to earlier beliefs1. Given that the activation of BAT results in increased energy expenditure and increased oxidation of lipid stores, it might constitute a promising target for the treatment of obesity and related metabolic disorders. Indeed, loss of BAT leads to obesity in mice, and the induction of BAT increases energy expenditure and is associated with a lean phenotype even in high-fat-diet-fed mice2. Enhanced thermogenesis in BAT is mediated by adrenergic activation.

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Figure 1: The BAT–liver–intestine axis contributes to microbiome modulation and adaptive thermogenesis in cold-exposed mice fed a high-fat and high-cholesterol diet.

Debbie Maizels/Springer Nature

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Authors and Affiliations

  1. Departments of Pediatrics and Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Folkert Kuipers

  2. Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Albert K Groen

  3. Department of Vascular Medicine, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands

    Albert K Groen

Authors
  1. Folkert Kuipers
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  2. Albert K Groen
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Correspondence to Folkert Kuipers.

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Kuipers, F., Groen, A. An unexpected role for bile acid synthesis in adaptation to low temperature. Nat Med 23, 800–802 (2017). https://doi.org/10.1038/nm.4365

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