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Microbiota depletion promotes browning of white adipose tissue and reduces obesity

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Published in Nature Medicine. 2015, vol. 21, no. 12, p. 1497-1503
Abstract Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity1. In response to cold or exercise, brown fat cells also emerge in the white adipose tissue (WAT; also known as beige cells), a process known as browning2–4. Here we show that the development of functional beige fat in the inguinal subcutaneous adipose tissue (ingSAT) and perigonadal visceral adipose tissue (pgVAT) is promoted by the depletion of microbiota either by means of antibiotic treatment or in germ-free mice. This leads to improved glucose tolerance and insulin sensitivity and decreased white fat and adipocyte size in lean mice, obese leptin-deficient (ob/ob) mice and high-fat diet (HFD)-fed mice. Such metabolic improvements are mediated by eosinophil infiltration, enhanced type 2 cytokine signaling and M2 macrophage polarization in the subcutaneous white fat depots of microbiota-depleted animals. The metabolic phenotype and the browning of the subcutaneous fat are impaired by the suppression of type 2 cytokine signaling, and they are reversed by recolonization of the antibiotic-treated or germfree mice with microbes. These results provide insight into the microbiota-fat signaling axis and beige-fat development in health and metabolic disease.
Keywords Adipocytes/cytology/drug effects/metabolismAdipose Tissue, Brown/drug effects/metabolismAdipose Tissue, White/drug effects/metabolismAnimalsCell Size/drug effectsCytokines/metabolismGene Expression Regulation/drug effectsGerm-Free LifeGlucose/metabolismGlucose Tolerance TestInsulin/pharmacologyIntra-Abdominal Fat/drug effects/metabolismMice, Inbred BALB CMice, Inbred C57BLMicrobiota/drug effectsObesity/microbiology/pathologyRNA, Messenger/genetics/metabolismSignal Transduction/drug effectsSubcutaneous Fat/drug effects/metabolism
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PMID: 26569380
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Other version: http://www.nature.com/doifinder/10.1038/nm.3994
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Research groups Laboratory of metabolic diseases (934)
Imagerie per-opératoire multi-modalité en radiologie interventionnelle (949)
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SUAREZ ZAMORANO, Nicolas et al. Microbiota depletion promotes browning of white adipose tissue and reduces obesity. In: Nature Medicine, 2015, vol. 21, n° 12, p. 1497-1503. https://archive-ouverte.unige.ch/unige:78973

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Deposited on : 2016-01-05

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