title: Different tumor necrosis factor-alpha-associated leptin expression in rats with dimethylnitrosamine and bile duct ligation-induced liver cirrhosis.
abstract: Although serum leptin concentrations are reported by several studies to increase in patients with liver cirrhosis, the mechanisms underpinning this increase remain unclear. Circulating tumor necrosis factor alpha (TNF-alpha) concentrations are also recognized to increase in liver cirrhosis. Furthermore, TNF-alpha administration to rodents results in increased expression and secretion of leptin from adipose tissue in a manner dependent on type 1 TNF-alpha receptor (TNF-RI). The present study was undertaken to examine adipose leptin expression and to explore potential relationships between leptin expression and TNF-alpha in subjects with liver cirrhosis. Liver cirrhosis was induced in male Sprague-Dawley rats by dimethylnitrosamine (DMN) administration or by common bile duct ligation (BDL). Ad libitum and pair-fed animals constituted controls. Serum leptin and TNF-alpha concentrations were determined by immunoassay. Gene expression was determined by the reverse transcription-polymerase chain reaction, and protein levels were measured by Western blotting. Serum leptin values after adjustment of body fat mass in DMN-treated rats were significantly higher than in pair-fed or ad libitum groups. Leptin mRNA and protein levels in epididymal fat in DMN rats increased by 1.8-fold and 2.3-fold, respectively, as compared with ad libitum controls, and by 4-fold and 6-fold, respectively, as compared with the pair-fed group. Epididymal TNF-alpha and membranous TNF-RI (mTNF-RI) concentrations were both 2.3 times higher in DMN rats than in ad libitum controls but did not differ between ad libitum and pair-fed groups. Adipose leptin protein levels correlated directly with TNF-alpha and mTNF-RI concentrations in combined DMN, ad libitum, and pair-fed rats (r=0.64 and r=0.49, respectively; P<.05). In BDL-treated rats, however, serum and adipose leptin concentrations were identical to those in ad libitum controls despite 2.1-fold and 2.4-fold increase in epididymal TNF-alpha and mTNF-RI, respectively. TNF-alpha administration to fasting control animals increased serum and adipose leptin concentrations significantly. The observed TNF-alpha-associated leptin up-regulation in DMN-induced, but not in BDL-induced, cirrhotic rats is consistent with distinctly different roles for TNF-alpha in rats with nonbiliary, as opposed to biliary, cirrhosis.
authors.affiliation: Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taiwan.
authors.forename: Shih Yi
authors.initials: SY
authors.lastname: Lin
authors.forename: Wen Yin
authors.initials: WY
authors.lastname: Chen
authors.forename: Yung Tsung
authors.initials: YT
authors.lastname: Chiu
authors.forename: Wen Jane
authors.initials: WJ
authors.lastname: Lee
authors.forename: Hurng Sheng
authors.initials: HS
authors.lastname: Wu
authors.forename: Wayne Huey-Herng
authors.initials: WH
authors.lastname: Sheu
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry; D000818:Animals; D001652:Bile Ducts / Q000601:surgery*; D001663:Bilirubin / Q000097:blood; D015153:Blotting, Western; D004128:Dimethylnitrosamine; D004435:Eating / Q000187:drug effects; D004822:Epididymis / Q000737:chemistry; D015870:Gene Expression; D007118:Immunoassay; D020738:Leptin / Q000032:analysis / Q000235:genetics* / Q000494:pharmacology; D008026:Ligation; D008099:Liver / Q000201:enzymology; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000494:pharmacology
chemical_list: D020738:Leptin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004128:Dimethylnitrosamine; D001663:Bilirubin