Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese Mice

Given the increasing prevalence of obesity, the white-to-beige adipocyte conversion has attracted interest as a target for obesity treatment. Gamma-aminobutyric acid (GABA) treatment can reduce obesity, but the underlying mechanism remains unclear. Here, we aimed to investigate the mechanism by whic...

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Main Authors: Xiaoyi Ma, Huanhuan Yan, Shubin Hong, Shuang Yu, Yingying Gong, Dide Wu, Yanbing Li, Haipeng Xiao
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/15/2/456
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author Xiaoyi Ma
Huanhuan Yan
Shubin Hong
Shuang Yu
Yingying Gong
Dide Wu
Yanbing Li
Haipeng Xiao
author_facet Xiaoyi Ma
Huanhuan Yan
Shubin Hong
Shuang Yu
Yingying Gong
Dide Wu
Yanbing Li
Haipeng Xiao
author_sort Xiaoyi Ma
collection DOAJ
description Given the increasing prevalence of obesity, the white-to-beige adipocyte conversion has attracted interest as a target for obesity treatment. Gamma-aminobutyric acid (GABA) treatment can reduce obesity, but the underlying mechanism remains unclear. Here, we aimed to investigate the mechanism by which GABA triggers weight loss by improving the beiging of inguinal white adipose tissue (iWAT) and the role of gut microbiota in this process. The results showed that GABA reduced body weight and adipose inflammation and promoted the expression of thermogenic genes in the iWAT. The 16S rRNA sequence analysis of gut microbiota showed that GABA treatment increased the relative abundance of Bacteroidetes, Akkermansia, and Romboutsia and reduced that of Firmicutes and Erysipelatoclostridium in obese mice. Additionally, serum metabolomic analysis revealed that GABA treatment increased 3-hydroxybutyrate and reduced oxidized lipid levels in obese mice. Spearman’s correlation analysis showed that Akkermansia and Romboutsia were negatively associated with the levels of oxidized lipids. Fecal microbiota transplantation analysis confirmed that the gut microbiota was involved in the white-to-beige adipocyte reconstruction by GABA. Overall, our findings suggest that GABA treatment may promote iWAT beiging through the gut microbiota in obese mice. GABA may be utilized to protect obese people against metabolic abnormalities brought on by obesity and gut dysbiosis.
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spelling doaj.art-0b205c8421924934b8fcee2e7f0bf3442023-11-30T23:52:03ZengMDPI AGNutrients2072-66432023-01-0115245610.3390/nu15020456Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese MiceXiaoyi Ma0Huanhuan Yan1Shubin Hong2Shuang Yu3Yingying Gong4Dide Wu5Yanbing Li6Haipeng Xiao7Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaPaul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, ChinaDepartment of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Geriatrics, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaGiven the increasing prevalence of obesity, the white-to-beige adipocyte conversion has attracted interest as a target for obesity treatment. Gamma-aminobutyric acid (GABA) treatment can reduce obesity, but the underlying mechanism remains unclear. Here, we aimed to investigate the mechanism by which GABA triggers weight loss by improving the beiging of inguinal white adipose tissue (iWAT) and the role of gut microbiota in this process. The results showed that GABA reduced body weight and adipose inflammation and promoted the expression of thermogenic genes in the iWAT. The 16S rRNA sequence analysis of gut microbiota showed that GABA treatment increased the relative abundance of Bacteroidetes, Akkermansia, and Romboutsia and reduced that of Firmicutes and Erysipelatoclostridium in obese mice. Additionally, serum metabolomic analysis revealed that GABA treatment increased 3-hydroxybutyrate and reduced oxidized lipid levels in obese mice. Spearman’s correlation analysis showed that Akkermansia and Romboutsia were negatively associated with the levels of oxidized lipids. Fecal microbiota transplantation analysis confirmed that the gut microbiota was involved in the white-to-beige adipocyte reconstruction by GABA. Overall, our findings suggest that GABA treatment may promote iWAT beiging through the gut microbiota in obese mice. GABA may be utilized to protect obese people against metabolic abnormalities brought on by obesity and gut dysbiosis.https://www.mdpi.com/2072-6643/15/2/456obesityGABAwhite adiposebeige adiposegut microbiota
spellingShingle Xiaoyi Ma
Huanhuan Yan
Shubin Hong
Shuang Yu
Yingying Gong
Dide Wu
Yanbing Li
Haipeng Xiao
Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese Mice
Nutrients
obesity
GABA
white adipose
beige adipose
gut microbiota
title Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese Mice
title_full Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese Mice
title_fullStr Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese Mice
title_full_unstemmed Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese Mice
title_short Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese Mice
title_sort gamma aminobutyric acid promotes beige adipocyte reconstruction by modulating the gut microbiota in obese mice
topic obesity
GABA
white adipose
beige adipose
gut microbiota
url https://www.mdpi.com/2072-6643/15/2/456
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