Loss of resistin ameliorates hyperlipidemia and hepatic steatosis in leptin-deficient mice.
Resistin has been linked to components of the metabolic syndrome, including obesity, insulin resistance, and hyperlipidemia. We hypothesized that resistin deficiency would reverse hyperlipidemia in genetic obesity. C57Bl/6J mice lacking resistin [resistin knockout (RKO)] had similar body weight and fat as wild-type mice when fed standard rodent chow or a high-fat diet. Nonetheless, hepatic steatosis, serum cholesterol, and very low-density lipoprotein (VLDL) secretion were decreased in diet-induced obese RKO mice. Resistin deficiency exacerbated obesity in ob/ob mice, but hepatic steatosis was drastically attenuated. Moreover, the levels of triglycerides, cholesterol, insulin, and glucose were reduced in ob/ob-RKO mice. The antisteatotic effect of resistin deficiency was related to reductions in the expression of genes involved in hepatic lipogenesis and VLDL export. Together, these results demonstrate a crucial role of resistin in promoting hepatic steatosis and hyperlipidemia in obese mice.
Singhal
Neel S
NS
Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania School of Medicine, 415 Curie Blvd., Philadelphia, PA 19104, USA.
Patel
Rajesh T
RT
Qi
Yong
Y
Lee
Yun-Sik
YS
Ahima
Rexford S
RS
D052242:Adiponectin / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D015331:Cohort Studies; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism*; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000172:deficiency* / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D052243:Resistin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D008079:Lipoproteins, VLDL; D052243:Resistin; D014280:Triglycerides; D002784:Cholesterol