title: Short-Chain Fatty Acid Acetate Stimulates Adipogenesis and Mitochondrial Biogenesis via GPR43 in Brown Adipocytes.
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.
authors.affiliation: Department of Translational and Experimental Medicine (J.H., B.K.T., G.K.D., G.T., V.P., M.K., J.C., H.S.R.), Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom; Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (I.K., B.K.T., G.K.D., H.S.R.) and Arden Tissue Bank (S.J.), Department of Pathology, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry CV2 2DX, United Kingdom; Birmingham Heartlands and Solihull Hospitals (B.K.T.), Heart of England National Health Service Foundation, National Health Service Trust, Birmingham B9 5SS, United Kingdom; Translational Research Institute (M.R.), Hamad Medical Corporation, 3050 Doha, Qatar; Jining Medical University (J.C.), 273100 Jining, People's Republic of China; and Aston Medical Research Institute (I.K., H.S.R.), Aston Medical School, Aston University, Birmingham B4 7ET, United Kingdom.
authors.forename: Jiamiao
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Translational and Experimental Medicine (J.H., B.K.T., G.K.D., G.T., V.P., M.K., J.C., H.S.R.), Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom; Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (I.K., B.K.T., G.K.D., H.S.R.) and Arden Tissue Bank (S.J.), Department of Pathology, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry CV2 2DX, United Kingdom; Birmingham Heartlands and Solihull Hospitals (B.K.T.), Heart of England National Health Service Foundation, National Health Service Trust, Birmingham B9 5SS, United Kingdom; Translational Research Institute (M.R.), Hamad Medical Corporation, 3050 Doha, Qatar; Jining Medical University (J.C.), 273100 Jining, People's Republic of China; and Aston Medical Research Institute (I.K., H.S.R.), Aston Medical School, Aston University, Birmingham B4 7ET, United Kingdom.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kyrou
authors.affiliation: Department of Translational and Experimental Medicine (J.H., B.K.T., G.K.D., G.T., V.P., M.K., J.C., H.S.R.), Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom; Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (I.K., B.K.T., G.K.D., H.S.R.) and Arden Tissue Bank (S.J.), Department of Pathology, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry CV2 2DX, United Kingdom; Birmingham Heartlands and Solihull Hospitals (B.K.T.), Heart of England National Health Service Foundation, National Health Service Trust, Birmingham B9 5SS, United Kingdom; Translational Research Institute (M.R.), Hamad Medical Corporation, 3050 Doha, Qatar; Jining Medical University (J.C.), 273100 Jining, People's Republic of China; and Aston Medical Research Institute (I.K., H.S.R.), Aston Medical School, Aston University, Birmingham B4 7ET, United Kingdom.
authors.forename: Bee K
authors.initials: BK
authors.lastname: Tan
authors.affiliation: Department of Translational and Experimental Medicine (J.H., B.K.T., G.K.D., G.T., V.P., M.K., J.C., H.S.R.), Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom; Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (I.K., B.K.T., G.K.D., H.S.R.) and Arden Tissue Bank (S.J.), Department of Pathology, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry CV2 2DX, United Kingdom; Birmingham Heartlands and Solihull Hospitals (B.K.T.), Heart of England National Health Service Foundation, National Health Service Trust, Birmingham B9 5SS, United Kingdom; Translational Research Institute (M.R.), Hamad Medical Corporation, 3050 Doha, Qatar; Jining Medical University (J.C.), 273100 Jining, People's Republic of China; and Aston Medical Research Institute (I.K., H.S.R.), Aston Medical School, Aston University, Birmingham B4 7ET, United Kingdom.
authors.forename: Georgios K
authors.initials: GK
authors.lastname: Dimitriadis
authors.affiliation: Department of Translational and Experimental Medicine (J.H., B.K.T., G.K.D., G.T., V.P., M.K., J.C., H.S.R.), Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom; Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (I.K., B.K.T., G.K.D., H.S.R.) and Arden Tissue Bank (S.J.), Department of Pathology, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry CV2 2DX, United Kingdom; Birmingham Heartlands and Solihull Hospitals (B.K.T.), Heart of England National Health Service Foundation, National Health Service Trust, Birmingham B9 5SS, United Kingdom; Translational Research Institute (M.R.), Hamad Medical Corporation, 3050 Doha, Qatar; Jining Medical University (J.C.), 273100 Jining, People's Republic of China; and Aston Medical Research Institute (I.K., H.S.R.), Aston Medical School, Aston University, Birmingham B4 7ET, United Kingdom.
authors.forename: Manjunath
authors.initials: M
authors.lastname: Ramanjaneya
authors.affiliation: Department of Translational and Experimental Medicine (J.H., B.K.T., G.K.D., G.T., V.P., M.K., J.C., H.S.R.), Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom; Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (I.K., B.K.T., G.K.D., H.S.R.) and Arden Tissue Bank (S.J.), Department of Pathology, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry CV2 2DX, United Kingdom; Birmingham Heartlands and Solihull Hospitals (B.K.T.), Heart of England National Health Service Foundation, National Health Service Trust, Birmingham B9 5SS, United Kingdom; Translational Research Institute (M.R.), Hamad Medical Corporation, 3050 Doha, Qatar; Jining Medical University (J.C.), 273100 Jining, People's Republic of China; and Aston Medical Research Institute (I.K., H.S.R.), Aston Medical School, Aston University, Birmingham B4 7ET, United Kingdom.
authors.forename: Gyanendra
authors.initials: G
authors.lastname: Tripathi
authors.affiliation: Department of Translational and Experimental Medicine (J.H., B.K.T., G.K.D., G.T., V.P., M.K., J.C., H.S.R.), Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom; Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (I.K., B.K.T., G.K.D., H.S.R.) and Arden Tissue Bank (S.J.), Department of Pathology, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry CV2 2DX, United Kingdom; Birmingham Heartlands and Solihull Hospitals (B.K.T.), Heart of England National Health Service Foundation, National Health Service Trust, Birmingham B9 5SS, United Kingdom; Translational Research Institute (M.R.), Hamad Medical Corporation, 3050 Doha, Qatar; Jining Medical University (J.C.), 273100 Jining, People's Republic of China; and Aston Medical Research Institute (I.K., H.S.R.), Aston Medical School, Aston University, Birmingham B4 7ET, United Kingdom.
authors.forename: Vanlata
authors.initials: V
authors.lastname: Patel
authors.affiliation: Department of Translational and Experimental Medicine (J.H., B.K.T., G.K.D., G.T., V.P., M.K., J.C., H.S.R.), Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom; Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (I.K., B.K.T., G.K.D., H.S.R.) and Arden Tissue Bank (S.J.), Department of Pathology, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry CV2 2DX, United Kingdom; Birmingham Heartlands and Solihull Hospitals (B.K.T.), Heart of England National Health Service Foundation, National Health Service Trust, Birmingham B9 5SS, United Kingdom; Translational Research Institute (M.R.), Hamad Medical Corporation, 3050 Doha, Qatar; Jining Medical University (J.C.), 273100 Jining, People's Republic of China; and Aston Medical Research Institute (I.K., H.S.R.), Aston Medical School, Aston University, Birmingham B4 7ET, United Kingdom.
authors.forename: Sean
authors.initials: S
authors.lastname: James
authors.affiliation: Department of Translational and Experimental Medicine (J.H., B.K.T., G.K.D., G.T., V.P., M.K., J.C., H.S.R.), Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom; Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (I.K., B.K.T., G.K.D., H.S.R.) and Arden Tissue Bank (S.J.), Department of Pathology, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry CV2 2DX, United Kingdom; Birmingham Heartlands and Solihull Hospitals (B.K.T.), Heart of England National Health Service Foundation, National Health Service Trust, Birmingham B9 5SS, United Kingdom; Translational Research Institute (M.R.), Hamad Medical Corporation, 3050 Doha, Qatar; Jining Medical University (J.C.), 273100 Jining, People's Republic of China; and Aston Medical Research Institute (I.K., H.S.R.), Aston Medical School, Aston University, Birmingham B4 7ET, United Kingdom.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Kawan
authors.affiliation: Department of Translational and Experimental Medicine (J.H., B.K.T., G.K.D., G.T., V.P., M.K., J.C., H.S.R.), Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom; Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (I.K., B.K.T., G.K.D., H.S.R.) and Arden Tissue Bank (S.J.), Department of Pathology, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry CV2 2DX, United Kingdom; Birmingham Heartlands and Solihull Hospitals (B.K.T.), Heart of England National Health Service Foundation, National Health Service Trust, Birmingham B9 5SS, United Kingdom; Translational Research Institute (M.R.), Hamad Medical Corporation, 3050 Doha, Qatar; Jining Medical University (J.C.), 273100 Jining, People's Republic of China; and Aston Medical Research Institute (I.K., H.S.R.), Aston Medical School, Aston University, Birmingham B4 7ET, United Kingdom.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Translational and Experimental Medicine (J.H., B.K.T., G.K.D., G.T., V.P., M.K., J.C., H.S.R.), Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom; Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (I.K., B.K.T., G.K.D., H.S.R.) and Arden Tissue Bank (S.J.), Department of Pathology, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry CV2 2DX, United Kingdom; Birmingham Heartlands and Solihull Hospitals (B.K.T.), Heart of England National Health Service Foundation, National Health Service Trust, Birmingham B9 5SS, United Kingdom; Translational Research Institute (M.R.), Hamad Medical Corporation, 3050 Doha, Qatar; Jining Medical University (J.C.), 273100 Jining, People's Republic of China; and Aston Medical Research Institute (I.K., H.S.R.), Aston Medical School, Aston University, Birmingham B4 7ET, United Kingdom.
authors.forename: Harpal S
authors.initials: HS
authors.lastname: Randeva
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology*; D052437:Adipocytes, Brown / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D001678:Organelle Biogenesis; D047495:PPAR gamma / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000071256:Uncoupling Protein 1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; C506481:Ffar2 protein, mouse; D047495:PPAR gamma; D043562:Receptors, G-Protein-Coupled; D000071256:Uncoupling Protein 1; D019342:Acetic Acid