Bacteroides spp. promotes branched-chain amino acid catabolism in brown fat and inhibits obesity

Naofumi Yoshida; Tomoya Yamashita; Tatsunori Osone; Tetsuya Hosooka; Masakazu Shinohara; Seiichi Kitahama; Kengo Sasaki; Daisuke Sasaki; Takeshi Yoneshiro; Tomohiro Suzuki; Takuo Emoto; Yoshihiro Saito; Genki Ozawa; Yushi Hirota; Yasuyuki Kitaura; Yoshiharu Shimomura; Yuko Okamatsu-Ogura; Masayuki Saito; Akihiko Kondo; Shingo Kajimura; Takeshi Inagaki; Wataru Ogawa; Takuji Yamada; Ken-Ichi Hirata

doi:10.1016/j.isci.2021.103342

Bacteroides spp. promotes branched-chain amino acid catabolism in brown fat and inhibits obesity

iScience. 2021 Oct 24;24(11):103342. doi: 10.1016/j.isci.2021.103342. eCollection 2021 Nov 19.

Authors

Naofumi Yoshida¹, Tomoya Yamashita^{1

2}, Tatsunori Osone³, Tetsuya Hosooka⁴, Masakazu Shinohara^{5

6}, Seiichi Kitahama⁷, Kengo Sasaki^{8

9}, Daisuke Sasaki⁸, Takeshi Yoneshiro¹⁰, Tomohiro Suzuki¹¹, Takuo Emoto¹, Yoshihiro Saito¹, Genki Ozawa¹², Yushi Hirota¹³, Yasuyuki Kitaura¹⁴, Yoshiharu Shimomura¹⁵, Yuko Okamatsu-Ogura¹⁶, Masayuki Saito¹⁶, Akihiko Kondo⁸, Shingo Kajimura¹⁷, Takeshi Inagaki¹¹, Wataru Ogawa¹³, Takuji Yamada³, Ken-Ichi Hirata¹

Affiliations

¹ Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 6500017, Japan.
² AMED-PRIME, Japan Agency for Medical Research and Development, 1-8-1 Inohana, Chuo-ku, Tokyo 1008152, Japan.
³ School and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Tokyo 1528550, Japan.
⁴ Laboratory of Nutritional Physiology, School of Food and Nutritional Sciences/Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka 4228526, Japan.
⁵ Division of Epidemiology, Kobe University Graduate School of Medicine, Kobe 6500017, Japan.
⁶ The Integrated Center for Mass Spectrometry, Graduate School of Medicine, Kobe University, Kobe 6500017, Japan.
⁷ Department of Metabolic and Bariatric Surgery, Center for Obesity, Diabetes and Endocrinology, Chibune General Hospital, Osaka 5550034, Japan.
⁸ Graduate School of Science, Technology and Innovation, Kobe University, Kobe 6578501, Japan.
⁹ Bio Palette Co., Ltd., Kobe 6500047, Japan.
¹⁰ Division of Metabolic Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 1538904, Japan.
¹¹ Laboratory of Epigenetics and Metabolism, Institute for Molecular and Cellular Regulation, Gunma University, Gunma 3718512, Japan.
¹² TechnoSuruga Laboratory Co., Ltd., Shizuoka 4240065, Japan.
¹³ Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 6500017, Japan.
¹⁴ Laboratory of Nutritional Biochemistry, Department of Applied Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 4648601, Japan.
¹⁵ Department of Food and Nutritional Sciences, College of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi 4878501, Japan.
¹⁶ Faculty of Veterinary Medicine, Hokkaido University, Sapporo 0600818, Japan.
¹⁷ Division of Endocrinology, Diabetes & Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

Abstract

The gut microbiome has emerged as a key regulator of obesity; however, its role in brown adipose tissue (BAT) metabolism and association with obesity remain to be elucidated. We found that the levels of circulating branched-chain amino acids (BCAA) and their cognate α-ketoacids (BCKA) were significantly correlated with the body weight in humans and mice and that BCAA catabolic defects in BAT were associated with obesity in diet-induced obesity (DIO) mice. Pharmacological systemic enhancement of BCAA catabolic activity reduced plasma BCAA and BCKA levels and protected against obesity; these effects were reduced in BATectomized mice. DIO mice gavaged with Bacteroides dorei and Bacteroides vulgatus exhibited improved BAT BCAA catabolism and attenuated body weight gain, which were not observed in BATectomized DIO mice. Our data have highlighted a possible link between the gut microbiota and BAT BCAA catabolism and suggest that Bacteroides probiotics could be used for treating obesity.

Keywords: Computer systems organization; Energy engineering; Energy systems.

Abstract

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