Microbiota depletion promotes browning of white adipose tissue and reduces obesity

Nicolas Suárez-Zamorano; Salvatore Fabbiano; Claire Chevalier; Ozren Stojanović; Didier J. Colin; Ana Stevanović; Christelle Veyrat-Durebex; Valentina Tarallo; Dorothée Rigo; Stéphane Germain; Miroslava Ilievska; Xavier Montet; Yann Seimbille; Siegfried Hapfelmeier; Mirko Trajkovski

doi:10.1038/nm.3994

Microbiota depletion promotes browning of white adipose tissue and reduces obesity

Nicolas Suárez-Zamorano
, Salvatore Fabbiano
, Claire Chevalier
, Ozren Stojanović
, Didier J. Colin
, Ana Stevanović
, Christelle Veyrat-Durebex
, Valentina Tarallo
, Dorothée Rigo
, Stéphane Germain
, Miroslava Ilievska
, Xavier Montet
, Yann Seimbille
, Siegfried Hapfelmeier
, Mirko Trajkovski^*

^*Corresponding author for this work

University of Geneva
University Hospital of Geneva
Alkaloid AD Skopje
University of Bern
University College London

Research output: Contribution to journal › Article › Academic › peer-review

375 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1497-1501
Number of pages	5
Journal	Nature Medicine
Volume	21
Issue number	12
DOIs	https://doi.org/10.1038/nm.3994
Publication status	Published - Dec 2015
Externally published	Yes

Bibliographical note

Funding Information:
We thank M. Gustafsson Trajkovska, C. Wollheim and R. Coppari for their discussions and critical reading of the manuscript; C. Darimont for help with bomb calorimetric measurements; P. Maechler and M. Karaca for help with and discussions about the OCR measurements; S. Startchik for help with image quantifications; ERC-2013-StG-281904 to S.H. for partial funding of the gnotobiotic research; and G. Waksman for support. The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 336607 (ERC-2013-StG-336607); the Louis-Jeantet Foundation; Fondation pour Recherches Médicales; Novartis Foundation (14B053) and the Swiss National Science Foundation (SNSF) Professorship (PP00P3_144886) to M.T.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/nm.3994

Cite this

Suárez-Zamorano, N., Fabbiano, S., Chevalier, C., Stojanović, O., Colin, D. J., Stevanović, A., Veyrat-Durebex, C., Tarallo, V., Rigo, D., Germain, S., Ilievska, M., Montet, X., Seimbille, Y., Hapfelmeier, S., & Trajkovski, M. (2015). Microbiota depletion promotes browning of white adipose tissue and reduces obesity. Nature Medicine, 21(12), 1497-1501. https://doi.org/10.1038/nm.3994

@article{1e14f979fb6d4a4eb2c0d3411d66a758,

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.",

author = "Nicolas Su{\'a}rez-Zamorano and Salvatore Fabbiano and Claire Chevalier and Ozren Stojanovi{\'c} and Colin, \{Didier J.\} and Ana Stevanovi{\'c} and Christelle Veyrat-Durebex and Valentina Tarallo and Doroth{\'e}e Rigo and St{\'e}phane Germain and Miroslava Ilievska and Xavier Montet and Yann Seimbille and Siegfried Hapfelmeier and Mirko Trajkovski",

note = "Funding Information: We thank M. Gustafsson Trajkovska, C. Wollheim and R. Coppari for their discussions and critical reading of the manuscript; C. Darimont for help with bomb calorimetric measurements; P. Maechler and M. Karaca for help with and discussions about the OCR measurements; S. Startchik for help with image quantifications; ERC-2013-StG-281904 to S.H. for partial funding of the gnotobiotic research; and G. Waksman for support. The research leading to these results has received funding from the European Research Council under the European Union{\textquoteright}s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 336607 (ERC-2013-StG-336607); the Louis-Jeantet Foundation; Fondation pour Recherches M{\'e}dicales; Novartis Foundation (14B053) and the Swiss National Science Foundation (SNSF) Professorship (PP00P3\_144886) to M.T.",

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month = dec,

doi = "10.1038/nm.3994",

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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 & Trajkovski, M 2015, 'Microbiota depletion promotes browning of white adipose tissue and reduces obesity', Nature Medicine, vol. 21, no. 12, pp. 1497-1501. https://doi.org/10.1038/nm.3994

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T1 - Microbiota depletion promotes browning of white adipose tissue and reduces obesity

AU - Suárez-Zamorano, Nicolas

AU - Fabbiano, Salvatore

AU - Chevalier, Claire

AU - Stojanović, Ozren

AU - Colin, Didier J.

AU - Stevanović, Ana

AU - Veyrat-Durebex, Christelle

AU - Tarallo, Valentina

AU - Rigo, Dorothée

AU - Germain, Stéphane

AU - Ilievska, Miroslava

AU - Montet, Xavier

AU - Seimbille, Yann

AU - Hapfelmeier, Siegfried

AU - Trajkovski, Mirko

N1 - Funding Information: We thank M. Gustafsson Trajkovska, C. Wollheim and R. Coppari for their discussions and critical reading of the manuscript; C. Darimont for help with bomb calorimetric measurements; P. Maechler and M. Karaca for help with and discussions about the OCR measurements; S. Startchik for help with image quantifications; ERC-2013-StG-281904 to S.H. for partial funding of the gnotobiotic research; and G. Waksman for support. The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 336607 (ERC-2013-StG-336607); the Louis-Jeantet Foundation; Fondation pour Recherches Médicales; Novartis Foundation (14B053) and the Swiss National Science Foundation (SNSF) Professorship (PP00P3_144886) to M.T.

PY - 2015/12

Y1 - 2015/12

N2 - 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.

AB - 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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DO - 10.1038/nm.3994

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SN - 1078-8956

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SP - 1497

EP - 1501

JO - Nature Medicine

JF - Nature Medicine

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ER -

Microbiota depletion promotes browning of white adipose tissue and reduces obesity

Abstract

Bibliographical note

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