Resistance to high-fat diet-induced obesity and altered expression of adipose-specific genes in HSL-deficient mice.
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.
Harada
Kenji
K
Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA.
Shen
Wen-Jun
WJ
Patel
Shailja
S
Natu
Vanita
V
Wang
Jining
J
Osuga
Jun-ichi
J
Ishibashi
Shun
S
Kraemer
Fredric B
FB
D000273:Adipose Tissue / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D004198:Disease Susceptibility; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D009747:Nutritional Physiological Phenomena; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
D004041:Dietary Fats; D008055:Lipids; D002787:Sterol Esterase