title: Central action of xenin affects the expression of lipid metabolism-related genes and proteins in mouse white adipose tissue.
abstract: Xenin is a gastrointestinal hormone that reduces food intake when administered centrally and it has been hypothesized that central action of xenin participates in the regulation of whole-body metabolism. The present study was performed to address this hypothesis by investigating the central effect of xenin on the expression of genes and proteins that are involved in the regulation of lipid metabolism in white adipose tissue (WAT). Male obese ob/ob mice received intracerebroventricular (i.c.v.) injections of xenin (5μg) twice 12h apart. Food intake and body weight change during a 24-h period after the first injection were measured. Epididymal WAT was collected at the end of the 24-h treatment period and levels of lipid metabolism-related genes and proteins were measured. Xenin treatment caused significant reductions in food intake and body weight compared to control vehicle treatment. Levels of fatty acid synthase (FASN) protein were significantly reduced by xenin treatment, while levels of adipose triglyceride lipase (Atgl) and beta-3 adrenergic receptor (Adrb3) mRNA and phosphorylated hormone sensitive lipase (Ser660-pHSL and Ser563-pHSL) were significantly increased by xenin treatment. These findings suggest that central action of xenin causes alterations in lipid metabolism in adipose tissue toward reduced lipogenesis and increased lipolysis, possibly contributing to xenin-induced body weight reduction. Thus, enhancing central action of xenin and its downstream targets may be possible targets for the treatment of obesity by reducing the amount of stored fat in adipose tissue.
authors.affiliation: Division of Endocrinology and Metabolic Disease, Department of Physiology & Pathophysiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada.
authors.forename: Sharma
authors.initials: S
authors.lastname: Bhavya
authors.affiliation: Division of Endocrinology and Metabolic Disease, Department of Physiology & Pathophysiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada.
authors.forename: Pei San
authors.initials: PS
authors.lastname: Lew
authors.affiliation: Division of Endocrinology and Metabolic Disease, Department of Physiology & Pathophysiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada. Electronic address: Tooru.Mizuno@umanitoba.ca.
authors.forename: Tooru M
authors.initials: TM
authors.lastname: Mizuno
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015870:Gene Expression / Q000187:drug effects*; D005990:Glycerol / Q000097:blood; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D051379:Mice; D009496:Neurotensin / Q000494:pharmacology*; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism; D000217:Acyltransferases
chemical_list: D064429:Fatty Acid Synthases; D005230:Fatty Acids, Nonesterified; D005990:Glycerol; D008049:Lipase; D009496:Neurotensin; D022702:Receptors, Adrenergic, beta-3; C077659:xenin 25; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases
keywords: Central nervous system; Energy partitioning; Gut hormone; Lipogenesis; Lipolysis; Obesity