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ACSS3 in brown fat drives propionate catabolism and its deficiency leads to autophagy and systemic metabolic dysfunction
Propionate is a gut microbial metabolite that has been reported to have controversial effects on metabolic health. Here we show that propionate is activated by acyl‐CoA synthetase short‐chain family member 3 (ACSS3), located on the mitochondrial inner membrane in brown adipocytes. Knockout of Acss3...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858619/ https://www.ncbi.nlm.nih.gov/pubmed/35184387 http://dx.doi.org/10.1002/ctm2.665 |
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author | Jia, Zhihao Chen, Xiyue Chen, Jingjuan Zhang, Lijia Oprescu, Stephanie N. Luo, Nanjian Xiong, Yan Yue, Feng Kuang, Shihuan |
author_facet | Jia, Zhihao Chen, Xiyue Chen, Jingjuan Zhang, Lijia Oprescu, Stephanie N. Luo, Nanjian Xiong, Yan Yue, Feng Kuang, Shihuan |
author_sort | Jia, Zhihao |
collection | PubMed |
description | Propionate is a gut microbial metabolite that has been reported to have controversial effects on metabolic health. Here we show that propionate is activated by acyl‐CoA synthetase short‐chain family member 3 (ACSS3), located on the mitochondrial inner membrane in brown adipocytes. Knockout of Acss3 gene (Acss3(–/–)) in mice reduces brown adipose tissue (BAT) mass but increases white adipose tissue (WAT) mass, leading to glucose intolerance and insulin resistance that are exacerbated by high‐fat diet (HFD). Intriguingly, Acss3(–/–) or HFD feeding significantly elevates propionate levels in BAT and serum, and propionate supplementation induces autophagy in cultured brown and white adipocytes. The elevated levels of propionate in Acss3(–/–) mice similarly drive adipocyte autophagy, and pharmacological inhibition of autophagy using hydroxychloroquine ameliorates obesity, hepatic steatosis and insulin resistance of the Acss3(–/–) mice. These results establish ACSS3 as the key enzyme for propionate metabolism and demonstrate that accumulation of propionate promotes obesity and Type 2 diabetes through triggering adipocyte autophagy. |
format | Online Article Text |
id | pubmed-8858619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88586192022-03-31 ACSS3 in brown fat drives propionate catabolism and its deficiency leads to autophagy and systemic metabolic dysfunction Jia, Zhihao Chen, Xiyue Chen, Jingjuan Zhang, Lijia Oprescu, Stephanie N. Luo, Nanjian Xiong, Yan Yue, Feng Kuang, Shihuan Clin Transl Med Research Articles Propionate is a gut microbial metabolite that has been reported to have controversial effects on metabolic health. Here we show that propionate is activated by acyl‐CoA synthetase short‐chain family member 3 (ACSS3), located on the mitochondrial inner membrane in brown adipocytes. Knockout of Acss3 gene (Acss3(–/–)) in mice reduces brown adipose tissue (BAT) mass but increases white adipose tissue (WAT) mass, leading to glucose intolerance and insulin resistance that are exacerbated by high‐fat diet (HFD). Intriguingly, Acss3(–/–) or HFD feeding significantly elevates propionate levels in BAT and serum, and propionate supplementation induces autophagy in cultured brown and white adipocytes. The elevated levels of propionate in Acss3(–/–) mice similarly drive adipocyte autophagy, and pharmacological inhibition of autophagy using hydroxychloroquine ameliorates obesity, hepatic steatosis and insulin resistance of the Acss3(–/–) mice. These results establish ACSS3 as the key enzyme for propionate metabolism and demonstrate that accumulation of propionate promotes obesity and Type 2 diabetes through triggering adipocyte autophagy. John Wiley and Sons Inc. 2022-02-20 /pmc/articles/PMC8858619/ /pubmed/35184387 http://dx.doi.org/10.1002/ctm2.665 Text en © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Jia, Zhihao Chen, Xiyue Chen, Jingjuan Zhang, Lijia Oprescu, Stephanie N. Luo, Nanjian Xiong, Yan Yue, Feng Kuang, Shihuan ACSS3 in brown fat drives propionate catabolism and its deficiency leads to autophagy and systemic metabolic dysfunction |
title | ACSS3 in brown fat drives propionate catabolism and its deficiency leads to autophagy and systemic metabolic dysfunction |
title_full | ACSS3 in brown fat drives propionate catabolism and its deficiency leads to autophagy and systemic metabolic dysfunction |
title_fullStr | ACSS3 in brown fat drives propionate catabolism and its deficiency leads to autophagy and systemic metabolic dysfunction |
title_full_unstemmed | ACSS3 in brown fat drives propionate catabolism and its deficiency leads to autophagy and systemic metabolic dysfunction |
title_short | ACSS3 in brown fat drives propionate catabolism and its deficiency leads to autophagy and systemic metabolic dysfunction |
title_sort | acss3 in brown fat drives propionate catabolism and its deficiency leads to autophagy and systemic metabolic dysfunction |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858619/ https://www.ncbi.nlm.nih.gov/pubmed/35184387 http://dx.doi.org/10.1002/ctm2.665 |
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