Kiskinis, Evangelos, Chatzeli, Lemonia, Curry, Edward, Kaforou, Myrsini, Frontini, Andrea, Cinti, Saverio, Montana, Giovanni, Parker, Malcolm G. and Christian, Mark (2014) RIP140 represses the “Brown-in-White” adipocyte program including a futile cycle of triacyclglycerol breakdown and synthesis. Molecular Endocrinology, Volume 28 (Number 3). pp. 344-356. doi:10.1210/me.2013-1254 ISSN 0888-8809.

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Abstract

Receptor-interacting protein 140 (RIP140) is a corepressor of nuclear receptors that is highly expressed in adipose tissues. We investigated the role of RIP140 in conditionally immortal preadipocyte cell lines prepared from white or brown fat depots. In white adipocytes, a large set of brown fat-associated genes was up-regulated in the absence of RIP140. In contrast, a relatively minor role can be ascribed to RIP140 in the control of basal gene expression in differentiated brown adipocytes because significant changes were observed only in Ptgds and Fabp3. The minor role of RIP140 in brown adipocytes correlates with the similar histology and uncoupling protein 1 and CIDEA staining in knockout compared with wild-type brown adipose tissue (BAT). In contrast, RIP140 knockout sc white adipose tissue (WAT) shows increased numbers of multilocular adipocytes with elevated staining for uncoupling protein 1 and CIDEA. Furthermore in a white adipocyte cell line, the markers of BRITE adipocytes, Tbx1, CD137, Tmem26, Cited1, and Epsti1 were repressed in the presence of RIP140 as was Prdm16. Microarray analysis of wild-type and RIP140-knockout white fat revealed elevated expression of genes associated with cold-induced expression or high expression in BAT. A set of genes associated with a futile cycle of triacylglycerol breakdown and resynthesis and functional assays revealed that glycerol kinase and glycerol-3-phosphate dehydrogenase activity as well as [3H]glycerol incorporation were elevated in the absence of RIP140. Thus, RIP140 blocks the BRITE program in WAT, preventing the expression of brown fat genes and inhibiting a triacylglycerol futile cycle, with important implications for energy homeostasis.

Item Type:	Journal Article
Subjects:	Q Science > QR Microbiology
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
Library of Congress Subject Headings (LCSH):	Protein-protein interactions, Brown adipose tissue
Journal or Publication Title:	Molecular Endocrinology
Publisher:	Endocrine Society
ISSN:	0888-8809
Official Date:	30 January 2014
Dates:	Date Event 30 January 2014 Published 22 January 2014 Accepted 21 August 2013 Submitted
Volume:	Volume 28
Number:	Number 3
Page Range:	pp. 344-356
DOI:	10.1210/me.2013-1254
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	28 December 2015
Date of first compliant Open Access:	28 December 2015
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Seventh Framework Programme (European Commission) (FP7), Lilian Voudouri Foundation, Genesis Research Trust
Grant number:	BB/H020233/1 (BBSRC), HEALTH-F2-2011-278373 (FP7)

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