1. Microbiota depletion promotes browning of white adipose tissue and reduces obesity.
- Author
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Suárez-Zamorano N, Fabbiano S, Chevalier C, Stojanović O, Colin DJ, Stevanović A, Veyrat-Durebex C, Tarallo V, Rigo D, Germain S, Ilievska M, Montet X, Seimbille Y, Hapfelmeier S, and Trajkovski M
- Subjects
- Adipocytes cytology, Adipocytes drug effects, Adipocytes metabolism, Adipose Tissue, Brown drug effects, Adipose Tissue, White drug effects, Animals, Cell Size drug effects, Cytokines metabolism, Gene Expression Regulation drug effects, Germ-Free Life, Glucose metabolism, Glucose Tolerance Test, Insulin pharmacology, Intra-Abdominal Fat drug effects, Intra-Abdominal Fat metabolism, Mice, Inbred BALB C, Mice, Inbred C57BL, RNA, Messenger genetics, RNA, Messenger metabolism, Signal Transduction drug effects, Subcutaneous Fat drug effects, Subcutaneous Fat metabolism, Adipose Tissue, Brown metabolism, Adipose Tissue, White metabolism, Microbiota drug effects, Obesity microbiology, Obesity pathology
- Abstract
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.
- Published
- 2015
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