title: Microbiota depletion promotes browning of white adipose tissue and reduces obesity.
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.
authors.affiliation: 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.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Suárez-Zamorano
authors.affiliation: 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.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Fabbiano
authors.affiliation: 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.
authors.forename: Claire
authors.initials: C
authors.lastname: Chevalier
authors.affiliation: 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.
authors.forename: Ozren
authors.initials: O
authors.lastname: Stojanović
authors.affiliation: University Hospital of Geneva, Centre for BioMedical Imaging (CIBM), Geneva, Switzerland.
authors.forename: Didier J
authors.initials: DJ
authors.lastname: Colin
authors.affiliation: 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.
authors.forename: Ana
authors.initials: A
authors.lastname: Stevanović
authors.affiliation: 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.
authors.forename: Christelle
authors.initials: C
authors.lastname: Veyrat-Durebex
authors.affiliation: 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.
authors.forename: Valentina
authors.initials: V
authors.lastname: Tarallo
authors.affiliation: 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.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Rigo
authors.affiliation: University Hospital of Geneva, Centre for BioMedical Imaging (CIBM), Geneva, Switzerland.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Germain
authors.affiliation: Alkaloid AD Skopje, Skopje, Republic of Macedonia.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Ilievska
authors.affiliation: University Hospital of Geneva, Division of radiology, Geneva, Switzerland.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montet
authors.affiliation: University Hospital of Geneva, Cyclotron unit, Division of Nuclear Medicine, Geneva, Switzerland.
authors.forename: Yann
authors.initials: Y
authors.lastname: Seimbille
authors.affiliation: University of Bern, Institute for Infectious Diseases, Bern, Switzerland.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Hapfelmeier
authors.affiliation: 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 College London (UCL), Division of Biosciences, Institute of Structural and Molecular Biology, London, UK.
authors.forename: Mirko
authors.initials: M
authors.lastname: Trajkovski
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D048429:Cell Size / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005856:Germ-Free Life; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000494:pharmacology; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects; D009765:Obesity / Q000382:microbiology* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050151:Subcutaneous Fat / Q000187:drug effects / Q000378:metabolism
chemical_list: D016207:Cytokines; D007328:Insulin; D012333:RNA, Messenger; D005947:Glucose