Obestatin and Nt8U influence glycerolipid metabolism and PPARgamma signaling in mice

ShreeRanga, Nagaraj and Raghavan, A. V. and Sudha, N. Rao and Uma, V. Manjappara (2014) Obestatin and Nt8U influence glycerolipid metabolism and PPARgamma signaling in mice. The International Journal of Biochemistry and Cell Biology, 53. pp. 414-422.

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Abstract

Obestatin, its N-terminal fragment and the N-terminal fragment analog Nt8U were previously shown toreduce food intake, gain in body weight and triglyceride levels in albino mice. To establish their mode ofaction, mRNA profiling of the epididymal adipose tissue of mice treated with these peptides were per-formed. The differential expressions were markedly indicative of their involvement in lipid metabolism.Obestatin showed a significant upregulation of the genes patatin-like phospholipase domain containing 3,diacylglycerol O-acyltransferase 2, monoglyceride lipase, aldo–keto reductase family 1, member 7 whichare involved in glycerolipid metabolism. It also upregulated peroxisome proliferator-activated receptorgamma, retinoid X receptor gamma, cluster of differentiation 36, adiponectin, C1Q and collagen domaincontaining, angiopoietin-like 4, lipoprotein lipase, stearoyl-coenzyme A and desaturase 3 involved in theperoxisome proliferator-activated receptor signaling pathway. Nt8U upregulated genes implicated in thesame two pathways but with lesser significance and also upregulated APOL2. The N-terminal fragmentthough differentially regulated a small subset of the genes differentially regulated by obestatin and Nt8U,no conclusive evidence was obtained as to assign a specific pathway for its mode of action. We hypoth-esize that reduced food intake brought about by obestatin and Nt8U triggers lipid catabolism. The freefatty acids and lysophosphatidic acid thus produced in turn activates peroxisome proliferator-activatedreceptor gamma and the genes involved in peroxisome proliferator-activated receptor signaling. All ofthem together lead to reduction in gain in bodyweight, stored fat and circulating lipids. These results alsocorrelate well with the observed efficacy of the peptides.

Item Type:	Article
Uncontrolled Keywords:	Obestatin Nt8U Peroxisome proliferator-activated receptor gamma Patatin-like phospholipase domain containing 3 Apolipoprotein L8
Subjects:	500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 25 Peptide Chemistry
Divisions:	Protein Chemistry and Technology
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	07 Nov 2016 08:38
Last Modified:	07 Nov 2016 08:38
URI:	http://ir.cftri.res.in/id/eprint/12399

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