Leptin deficiency, not obesity, protects mice from Con A-induced hepatitis.
Leptin-deficient ob/ob mice are protected from Con A-induced hepatitis. However, it is unclear whether leptin deficiency or obesity itself is responsible for this protection. To address this question, wild-type (WT) obese mice with high serum leptin levels were generated by injection of gold thioglucose (WT GTG). Both Con A-injected WT and WT GTG mice developed hepatitis, whereas no hepatic damage was observed in ob/ob mice. Moreover, TNF-alpha and IFN-gamma levels as well as expression of the activation marker CD69 were elevated in liver mononuclear cells of WT and WT GTG mice, but not in ob/ob mice following administration of Con A. The liver of WT and WT GTG mice had the same percentage of NK T cells, a lymphocyte population involved in Con A-induced hepatitis. This population decreased equally in both WT and WT GTG mice after Con A injection. In contrast, the liver of ob/ob mice contained 50% less NK T cells compared to WT and WT GTG mice. Furthermore, no decrease in NK T cells was observed in Con A-injected ob/ob mice. We conclude that leptin-deficiency, not obesity, is responsible for protection from Con A-induced hepatitis.
Siegmund
Britta
B
Department of Medicine, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
Lear-Kaul
Kelly C
KC
Faggioni
Raffaella
R
Fantuzzi
Giamila
G
D000818:Animals; D006051:Aurothioglucose; D001835:Body Weight; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003208:Concanavalin A / Q000633:toxicity*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D020738:Leptin / Q000097:blood / Q000172:deficiency*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D006051:Aurothioglucose; D007371:Interferon-gamma