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

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.

SUBMITTER: Yoshida N

PROVIDER: S-EPMC8586802 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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

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

iScience 20211024 11

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 ...[more]

PMID: 34805797

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Project description:Despite the role of branched-chain amino acids (BCAAs) in physiological processes such as nutrient signaling and protein synthesis, there is ongoing debate about the link between circulating BCAAs and insulin resistance (IR) in various populations. In healthy women, IR mildly increases during pregnancy, whereas both BCAAs and markers of BCAA catabolism decrease, indicating that fetal growth is being prioritized. Exercise reduces IR in nonpregnant adults, but less is known about the effect of exercise during pregnancy in women with obesity on IR and BCAA breakdown. The aim of this study was to determine the effect of a moderate-intensity exercise intervention during pregnancy on maternal circulating BCAAs and markers of BCAA catabolism [short-chain acylcarnitines (ACs)], and their associations with IR. Healthy obese [n = 80, means ± SD; body mass index (BMI): 36.9 ± 5.7 kg/m2] pregnant women were randomized into an exercise (n = 40, aerobic/resistance 3×/wk, ∼13th gestation week until birth) or a nonexercise control (n = 40) group. Blood was collected at 12.2 ± 0.5 and 36.0 ± 0.4 gestation weeks and analyzed for BCAA-derived acylcarnitine concentrations as markers of BCAA breakdown toward oxidative pathways, and glucose and insulin concentrations [updated homeostatic model assessment of IR (HOMA2-IR)]. After adjusting for HOMA2-IR, there were no interaction effects of group by time. In addition, there was a main positive effect of time on HOMA2-IR (12 wk: 2.3 ± 0.2, 36 wk: 3.0 ± 0.2, P = 0.003). A moderate-intensity exercise intervention during pregnancy in women with obesity was not associated with changes in BCAA-derived ACs versus standard of care. The decrease in BCAA-derived ACs throughout gestation could not be explained by IR.NEW & NOTEWORTHY This research showed an increase in insulin resistance (IR) and decrease in branched-chain amino acid catabolism throughout gestation in women with obesity, and addition of a moderate exercise intervention (known to attenuate IR in nonpregnant populations) did not alter these shifts. Findings provide support for metabolic safety of exercise during pregnancy.

Dataset Information

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

Publications

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

Similar Datasets

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