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

Jiamiao Hu, Ioannis Kyrou, Bee K. Tan, Georgios K. Dimitriadis, Manjunath Ramanjaneya, Gyanendra Tripathi, Vanlata Patel, Sean James, Mohamed Kawan, Jing Chen, Harpal S. Randeva*

*Corresponding author for this work

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)1881-1894
Number of pages14
JournalEndocrinology
Volume157
Issue number5
Early online date18 Mar 2016
DOIs
Publication statusPublished - May 2016

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    Hu, J., Kyrou, I., Tan, B. K., Dimitriadis, G. K., Ramanjaneya, M., Tripathi, G., Patel, V., James, S., Kawan, M., Chen, J., & Randeva, H. S. (2016). Short-chain fatty acid acetate stimulates adipogenesis and mitochondrial biogenesis via GPR43 in brown adipocytes. Endocrinology, 157(5), 1881-1894. https://doi.org/10.1210/en.2015-1944