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Nat Med. 2015 Dec;21(12):1497-1501. doi: 10.1038/nm.3994. Epub 2015 Nov 16.

Microbiota depletion promotes browning of white adipose tissue and reduces obesity.

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University of Geneva, Faculty of Medicine, Department of Cell Physiology and Metabolism, Centre Médical Universitaire (CMU), Geneva, Switzerland.
University of Geneva, Diabetes Centre, Faculty of Medicine, Geneva, Switzerland.
University Hospital of Geneva, Centre for BioMedical Imaging (CIBM), Geneva, Switzerland.
Alkaloid AD Skopje, Skopje, Republic of Macedonia.
University Hospital of Geneva, Division of radiology, Geneva, Switzerland.
University Hospital of Geneva, Cyclotron unit, Division of Nuclear Medicine, Geneva, Switzerland.
University of Bern, Institute for Infectious Diseases, Bern, Switzerland.
University College London (UCL), Division of Biosciences, Institute of Structural and Molecular Biology, London, UK.
Contributed equally


Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity. 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 browning. 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 germ-free mice with microbes. These results provide insight into the microbiota-fat signaling axis and beige-fat development in health and metabolic disease.

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