Title : Resistance to high-fat diet-induced obesity and altered expression of adipose-specific genes in HSL-deficient mice - Harada_2003_Am.J.Physiol.Endocrinol.Metab_285_E1182 |
Author(s) : Harada K , Shen WJ , Patel S , Natu V , Wang J , Osuga J , Ishibashi S , Kraemer FB |
Ref : American Journal of Physiology Endocrinol Metab , 285 :E1182 , 2003 |
Abstract :
To elucidate the role of hormone-sensitive lipase (HSL) in diet-induced obesity, HSL-deficient (HSL-/-) and wild-type mice were fed normal chow or high-fat diets. HSL-/- mice were resistant to diet-induced obesity showing higher core body temperatures. Weight and triacylglycerol contents were decreased in white adipose tissue (WAT) but increased in both brown adipose tissue (BAT) and liver of HSL-/- mice. Serum insulin levels in the fed state and tumor necrosis factor-alpha mRNA levels in adipose tissues were higher, whereas serum levels of adipocyte complement-related protein of 30 kDa (ACRP30)/adiponectin and leptin, as well as mRNA levels of ACRP30/adiponectin, leptin, resistin, and adipsin in WAT, were lower in HSL-/- mice than in controls. Expression of transcription factors associated with adipogenesis (peroxisome proliferator-activated receptor-gamma, CAAT/enhancer-binding protein-alpha) and lipogenesis (carbohydrate response element-binding protein, adipocyte determination- and differentiation-dependent factor-1/sterol regulatory element-binding protein-1c), as well as of adipose differentiation markers (adipocyte lipid-binding protein, perilipin, lipoprotein lipase), lipogenic enzymes (glycerol-3-phosphate acyltransferase, acyl-CoA:diacylglycerol acyltransferase-1 and -2, fatty acid synthase, ATP citrate lyase) and insulin signaling proteins (insulin receptor, insulin receptor substrate-1, GLUT4), was suppressed in WAT but not in BAT of HSL-/- mice. In contrast, expression of genes associated with cholesterol metabolism (sterol-regulatory element-binding protein-2, 3-hydroxy-3-methylglutaryl-CoA reductase, acyl-CoA:cholesterol acyltransferase-1) and thermogenesis (uncoupling protein-2) was upregulated in both WAT and BAT of HSL-/- mice. Our results suggest that impaired lipolysis in HSL deficiency affects lipid metabolism through alterations of adipose differentiation and adipose-derived hormone levels. |
PubMedSearch : Harada_2003_Am.J.Physiol.Endocrinol.Metab_285_E1182 |
PubMedID: 12954598 |
Harada K, Shen WJ, Patel S, Natu V, Wang J, Osuga J, Ishibashi S, Kraemer FB (2003)
Resistance to high-fat diet-induced obesity and altered expression of adipose-specific genes in HSL-deficient mice
American Journal of Physiology Endocrinol Metab
285 :E1182
Harada K, Shen WJ, Patel S, Natu V, Wang J, Osuga J, Ishibashi S, Kraemer FB (2003)
American Journal of Physiology Endocrinol Metab
285 :E1182