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Short-chain fatty acid acetate stimulates adipogenesis and mitochondrial biogenesis via GPR43 in brown adipocytes

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Hu, Jiamiao, Kyrou, Ioannis, Tan, Bee K., Dimitriadis, Georgios K., Ramanjaneya, Manjunath, Tripathi, Gyanendra, Patel, Vanlata H., James, Sean G., Kawan, Mohamed, Chen, Jing and Randeva, Harpal S. (2016) Short-chain fatty acid acetate stimulates adipogenesis and mitochondrial biogenesis via GPR43 in brown adipocytes. Endocrinology, 157 (5). pp. 1881-1894. doi:10.1210/en.2015-1944 ISSN 0013-7227.

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Official URL: http://dx.doi.org/10.1210/en.2015-1944

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Abstract

Short-chain fatty acids play crucial roles in a range of physiological functions. However, the effects of short-chain fatty acids on brown adipose tissue have not been fully investigated. We examined the role of acetate, a short-chain fatty acid formed by fermentation in the gut, in the regulation of brown adipocyte metabolism. Our results show that acetate up-regulates AP2, PGC-1α and UCP1 expression and affects the morphological changes of brown adipocytes during adipogenesis. Moreover, an increase in mitochondrial biogenesis was observed after acetate treatment. Acetate also elicited the activation of ERK and CREB, and these responses were sensitive to G(i/o)-type G protein inactivator, Gβγ-subunit inhibitor, PLC inhibitor, PKC inhibitor and MEK inhibitor, indicating a role for the G(i/o)βγ/PLC/PKC/MEK signalling pathway in these responses. These effects of acetate were mimicked by treatment with 4-CMTB, a synthetic GPR43 agonist, and were impaired in GPR43 knock-down cells. Taken together, our results indicate that acetate may have important physiological roles in brown adipocytes through activation of GPR43.

Item Type: Journal Article
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title: Endocrinology
Publisher: Endocrine Society
ISSN: 0013-7227
Official Date: 1 May 2016
Dates:
DateEvent
1 May 2016Published
18 March 2016Available
14 March 2016Accepted
7 November 2015Submitted
Volume: 157
Number: 5
Page Range: pp. 1881-1894
DOI: 10.1210/en.2015-1944
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Copyright Holders: Endocrine Society
Funder: General Charities of the City of Coventry (GCCC)
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