title: Obestatin and Nt8U influence glycerolipid metabolism and PPAR gamma signaling in mice.
abstract: Obestatin, its N-terminal fragment and the N-terminal fragment analog Nt8U were previously shown to reduce food intake, gain in body weight and triglyceride levels in albino mice. To establish their mode of action, mRNA profiling of the epididymal adipose tissue of mice treated with these peptides were performed. 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 which are involved in glycerolipid metabolism. It also upregulated peroxisome proliferator-activated receptor gamma, retinoid X receptor gamma, cluster of differentiation 36, adiponectin, C1Q and collagen domain containing, angiopoietin-like 4, lipoprotein lipase, stearoyl-coenzyme A and desaturase 3 involved in the peroxisome proliferator-activated receptor signaling pathway. Nt8U upregulated genes implicated in the same two pathways but with lesser significance and also upregulated APOL2. The N-terminal fragment though 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 hypothesize that reduced food intake brought about by obestatin and Nt8U triggers lipid catabolism. The free fatty acids and lysophosphatidic acid thus produced in turn activates peroxisome proliferator-activated receptor gamma and the genes involved in peroxisome proliferator-activated receptor signaling. All of them together lead to reduction in gain in bodyweight, stored fat and circulating lipids. These results also correlate well with the observed efficacy of the peptides.
authors.affiliation: Department of Protein Chemistry and Technology, CSIR-Central Food Technological Research Institute, Mysore 570020, India.
authors.forename: ShreeRanga
authors.initials: S
authors.lastname: Nagaraj
authors.affiliation: Department of Protein Chemistry and Technology, CSIR-Central Food Technological Research Institute, Mysore 570020, India.
authors.forename: Angad V
authors.initials: AV
authors.lastname: Raghavan
authors.affiliation: Genotypic Technology Pvt. Ltd., No. 259, Apoorva, 4th Cross, 80Ft Road, RMV II Stage, Bangalore 560094, India.
authors.forename: Sudha N
authors.initials: SN
authors.lastname: Rao
authors.affiliation: Department of Protein Chemistry and Technology, CSIR-Central Food Technological Research Institute, Mysore 570020, India. Electronic address: umamanjappara@cftri.res.in.
authors.forename: Uma V
authors.initials: UV
authors.lastname: Manjappara
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects* / Q000235:genetics; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008066:Lipolysis / Q000187:drug effects; D051379:Mice; D047495:PPAR gamma / Q000096:biosynthesis*; D036361:Peptide Hormones / Q000008:administration & dosage* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C000596354:Nt8U peptide; D047495:PPAR gamma; D036361:Peptide Hormones; C512328:obestatin, mouse
keywords: Apolipoprotein L 8; Nt8U; Obestatin; Patatin-like phospholipase domain containing 3; Peroxisome proliferator-activated receptor gamma