Irshad, Zehra, Dimitri, Federica, Christian, Mark and Zammit, Victor A. (2017) Diacylglycerol acyltransferase 2 links glucose utilization to fatty acid oxidation in the brown adipocytes. Journal of Lipid Research, 58 (1). pp. 15-30. doi:10.1194/jlr.M068197 ISSN 0022-2275.

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Abstract

Brown adipose tissue uptake of glucose and fatty acids is very high during non-shivering thermogenesis. Adrenergic stimulation markedly increases glucose uptake, de novo lipogenesis and FA oxidation simultaneously. The mechanism that enables this concerted response has hitherto been unknown. Here we find that in a primary brown adipocytes and brown adipocyte-derived cell line (IMBAT-1) acute inhibition and longer-term knockdown of DGAT2 links the increased de novo synthesis of fatty acids from glucose to a pool of TG which is simultaneously hydrolysed, providing FA for mitochondrial oxidation. DGAT1 does not contribute to this pathway, but uses exogenous FA and glycerol to synthesise a functionally distinct pool of TG to which DGAT2 also contributes to it. The DGAT2-dependent channelling of 14C from glucose into TG and CO2 was reproduced in β3-agonist-stimulated primary brown adipocytes. Knockdown of DGAT2 in IMBAT-1 affected the mRNA levels of several genes important in FA activation and esterification. Therefore, in β3-agonist activated brown adipocytes, DGAT2 specifically enables channelling of de novo synthesised FA into a rapidly mobilised pool of TG which is simultaneously hydrolysed to provide substrates for mitochondrial fatty acid oxidation.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Metabolism, Brown adipose tissue
Journal or Publication Title:	Journal of Lipid Research
Publisher:	American Society for Biochemistry and Molecular Biology, Inc.
ISSN:	0022-2275
Official Date:	January 2017
Dates:	Date Event January 2017 Published 11 November 2016 Available 6 November 2016 Accepted 5 April 2016 Submitted
Volume:	58
Number:	1
Page Range:	pp. 15-30
DOI:	10.1194/jlr.M068197
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Copyright Holders:	Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.
Description:	Free access to pdf
Date of first compliant deposit:	5 January 2017
Date of first compliant Open Access:	5 January 2017
Funder:	Medical Research Council (Great Britain) (MRC)
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID UNSPECIFIED [MRC] Medical Research Council http://dx.doi.org/10.13039/501100000265

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