title: Alteration in body composition in the portacaval anastamosis rat is mediated by increased expression of myostatin.
abstract: The portacaval anastamosis (PCA) rat is a model to examine nutritional consequences of portosystemic shunting in cirrhosis. Alterations in body composition and mechanisms of diminished fat mass following PCA were examined. Body composition of male Sprague-Dawley rats with end-to-side PCA and pair-fed sham-operated (SO) controls were studied 3 wk after surgery by chemical carcass analysis (n=8 each) and total body electrical conductivity (n=6 each). Follistatin, a myostatin antagonist, or vehicle was administered to PCA and SO rats (n=8 in each group) to examine whether myostatin regulated fat mass following PCA. The expression of lipogenic and lipolytic genes in white adipose tissue (WAT) was quantified by real-time PCR. Body weight, fat-free mass, fat mass, organ weights, and food efficiency were significantly lower (P < 0.001) in the PCA than SO rats. Adipocyte size and triglyceride content of epididymal fat in PCA rats were significantly lower (P < 0.01) than in SO rats. Myostatin expression was higher in the WAT of PCA compared with SO rats and was accompanied by an increase in phospho-AMP kinase Thr(172). Follistatin increased whole body fat and WAT mass, adipocyte size, and expression of lipogenic genes in WAT in PCA, but not in SO rats. Myostatin and phospho-AMP kinase protein and lipolytic gene expression were lower with follistatin. We conclude that PCA results in loss of fat mass due to an increased expression of myostatin in adipose tissue with lower lipogenic and higher fatty acid oxidation gene expression.
authors.affiliation: Dept. of Gastroenterology and Pathobiology, Cleveland Clinic Foundation, Lerner Research Institute, OH 44195, USA. dasaras@ccf.org
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Dasarathy
authors.forename: Sean
authors.initials: S
authors.lastname: Muc
authors.forename: Ashok
authors.initials: A
authors.lastname: Runkana
authors.forename: Kevin Daniel
authors.initials: KD
authors.lastname: Mullen
authors.forename: Kristine
authors.initials: K
authors.lastname: Kaminsky-Russ
authors.forename: Arthur Joseph
authors.initials: AJ
authors.lastname: McCullough
mesh_terms: D052436:Adipose Tissue, White / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001823:Body Composition / Q000187:drug effects / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism; D038681:Follistatin / Q000494:pharmacology; D008297:Male; D055435:Myostatin / Q000096:biosynthesis*; D010084:Oxidation-Reduction; D011167:Portacaval Shunt, Surgical; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005227:Fatty Acids; D038681:Follistatin; D055435:Myostatin