Oral administration of branched-chain amino acids ameliorates high-fat diet-induced metabolic-associated fatty liver disease via gut microbiota-associated mechanisms

Ranran Zhang; Hongna Mu; Ziyun Li; Jie Zeng; Qi Zhou; Hongxia Li; Siming Wang; Xianghui Li; Xianghui Zhao; Liang Sun; Wenxiang Chen; Jun Dong; Ruiyue Yang

doi:10.3389/fmicb.2022.920277

Oral administration of branched-chain amino acids ameliorates high-fat diet-induced metabolic-associated fatty liver disease via gut microbiota-associated mechanisms

Front Microbiol. 2022 Jul 22:13:920277. doi: 10.3389/fmicb.2022.920277. eCollection 2022.

Authors

Ranran Zhang^{1

2}, Hongna Mu¹, Ziyun Li¹, Jie Zeng³, Qi Zhou¹, Hongxia Li¹, Siming Wang¹, Xianghui Li¹, Xianghui Zhao¹, Liang Sun¹, Wenxiang Chen^{1

3}, Jun Dong¹, Ruiyue Yang^{1

2}

Affiliations

¹ The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, China.
² Institute of Geriatrics, Peking University Fifth School of Clinical Medicine, Beijing, China.
³ National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China.

Abstract

Branched-chain amino acids (BCAAs), essential amino acids for the human body, are mainly obtained from food. High levels of BCAAs in circulation are considered as potential markers of metabolic-associated fatty liver disease (MAFLD) in humans. However, there are conflicting reports about the effects of supplement of BCAAs on MAFLD, and research on BCAAs and gut microbiota is not comprehensive. Here, C57BL/6J mice were fed with a high-fat diet with or without BCAAs to elucidate the effects of BCAAs on the gut microbiota and metabolic functions in a mouse model of MAFLD. Compared to high-fat diet (HFD) feeding, BCAA supplementation significantly reduced the mouse body weight, ratio of liver/body weight, hepatic lipid accumulation, serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and alanine aminotransferase (ALT), and the expressions of the lipogenesis-related enzymes Fas, Acc, and Scd-1 and increased expressions of the lipolysis-related enzymes Cpt1A and Atgl in the liver. BCAAs supplementation also counteracted HFD-induced elevations in serum BCAAs levels by stimulating the enzymatic activity of BCKDH. Furthermore, BCAAs supplementation markedly improved the gut bacterial diversity and altered the gut microbiota composition and abundances, especially those of genera, in association with MAFLD and BCAAs metabolism. These data suggest that BCAA treatment improves HFD-induced MAFLD through mechanisms involving intestinal microbes.

Keywords: LC–MS/MS; branched-chain amino acids; branched-chain amino acids metabolism; gut microbiota dysbiosis; lipometabolism; metabolic-associated fatty liver disease.