In:
Clinical and Translational Medicine, Wiley, Vol. 12, No. 2 ( 2022-02)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2001-1326
,
2001-1326
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
2697013-2
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