Microbiota depletion promotes browning of white adipose tissue and reduces obesity

• Published in: Nature medicine Vol. 21; no. 12; pp. 1497 - 1501
• Main Authors: Suárez-Zamorano, Nicolas, Fabbiano, Salvatore, Chevalier, Claire, Stojanović, Ozren, Colin, Didier J, Stevanović, Ana, Veyrat-Durebex, Christelle, Tarallo, Valentina, Rigo, Dorothée, Germain, Stéphane, Ilievska, Miroslava, Montet, Xavier, Seimbille, Yann, Hapfelmeier, Siegfried, Trajkovski, Mirko
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2015; Nature Publishing Group
• Subjects: 13/51; 14/63; 38/77; 59/78; 631/326/2565/2134; 631/443/319/1642/137/773; 631/443/319/1642/393; 631/443/319/2723; 64/110; 64/60; 692/308/575; 96/31; Adipocytes - cytology; Adipocytes - drug effects; Adipocytes - metabolism; Adipose tissue; Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; Adipose tissues; Animals; Biomedicine; Body fat; Cancer Research; Care and treatment; Cell Size - drug effects; Composition; Cytokines - metabolism; Development and progression; Diseases; Gene Expression Regulation - drug effects; Germ-Free Life; Glucose; Glucose - metabolism; Glucose Tolerance Test; Health aspects; Infectious Diseases; Insulin; Insulin - pharmacology; Intra-Abdominal Fat - drug effects; Intra-Abdominal Fat - metabolism; Leptin; letter; Macrophages; Metabolic Diseases; Metabolic disorders; Mice, Inbred BALB C; Mice, Inbred C57BL; Microbiota (Symbiotic organisms); Microbiota - drug effects; Microorganisms; Molecular Medicine; Neurosciences; Obesity; Obesity - microbiology; Obesity - pathology; Pregnancy; Prevention; Recolonization; Risk factors; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - drug effects; Subcutaneous Fat - drug effects; Subcutaneous Fat - metabolism; Europe
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.3994

Browning of white adipose tissue is induced by depletion of the microbiota, improving metabolic disease and reducing obesity. Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity 1 . 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 2 , 3 , 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 germ-free mice with microbes. These results provide insight into the microbiota-fat signaling axis and beige-fat development in health and metabolic disease.