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

Hu, Jiamiao, Kyrou, Ioannis, Tan, Bee K., Dimitriadis, Georgios K., Ramanjaneya, Manjunath, Tripathi, Gyanendra, Patel, Vanlata, James, Sean, 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.

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 adipocyte protein 2, peroxisomal proliferator-activated receptor-γ coactivator-1α, and uncoupling protein-1 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 cAMP response element-binding protein, and these responses were sensitive to G(i/o)-type G protein inactivator, Gβγ-subunit inhibitor, phospholipase C inhibitor, and MAPK kinase inhibitor, indicating a role for the G(i/o)βγ/phospholipase C/protein kinase C/MAPK kinase signaling pathway in these responses. These effects of acetate were mimicked by treatment with 4-chloro-α-(1-methylethyl)-N-2-thiazolylbenzeneacetamide, a synthetic G protein-coupled receptor 43 (GPR43) agonist and were impaired in GPR43 knockdown cells. Taken together, our results indicate that acetate may have important physiological roles in brown adipocytes through the activation of GPR43.

Publication DOI: https://doi.org/10.1210/en.2015-1944
Divisions: Aston Medical School
Uncontrolled Keywords: Endocrinology
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2016-05
Authors: Hu, Jiamiao
Kyrou, Ioannis ( 0000-0002-6997-3439)
Tan, Bee K.
Dimitriadis, Georgios K.
Ramanjaneya, Manjunath
Tripathi, Gyanendra
Patel, Vanlata
James, Sean
Kawan, Mohamed
Chen, Jing
Randeva, Harpal S.

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