title: Altered hepatic lipid metabolism contributes to nonalcoholic fatty liver disease in leptin-deficient Ob/Ob mice.
abstract: Nonalcoholic fatty liver disease (NAFLD) is strongly linked to obesity, insulin resistance, and abnormal hepatic lipid metabolism; however, the precise regulation of these processes remains poorly understood. Here we examined genes and proteins involved in hepatic oxidation and lipogenesis in 14-week-old leptin-deficient Ob/Ob mice, a commonly studied model of obesity and hepatic steatosis. Obese Ob/Ob mice had increased fasting glucose, insulin, and calculated HOMA-IR as compared with lean wild-type (WT) mice. Ob/Ob mice also had greater liver weights, hepatic triglyceride (TG) content, and markers of de novo lipogenesis, including increased hepatic gene expression and protein content of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD-1), as well as elevated gene expression of PPARγ and SREBP-1c compared with WT mice. While hepatic mRNA levels for PGC-1α, PPARα, and TFAM were elevated in Ob/Ob mice, measures of mitochondrial function (β-HAD activity and complete (to CO(2)) and total mitochondrial palmitate oxidation) and mitochondrial OXPHOS protein subunits I, III, and V content were significantly reduced compared with WT animals. In summary, reduced hepatic mitochondrial content and function and an upregulation in de novo lipogenesis contribute to obesity-associated NAFLD in the leptin-deficient Ob/Ob mouse.
authors: Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA.
authors: James W
authors: JW
authors: Perfield
authors: Laura C
authors: LC
authors: Ortinau
authors: R Taylor
authors: RT
authors: Pickering
authors: Meghan L
authors: ML
authors: Ruebel
authors: Grace M
authors: GM
authors: Meers
authors: R Scott
authors: RS
authors: Rector
mesh_terms: D000818:Animals; D005234:Fatty Liver / Q000209:etiology*; D007333:Insulin Resistance; D020738:Leptin / Q000172:deficiency*; D050356:Lipid Metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008930:Mitochondria, Liver / Q000737:chemistry / Q000502:physiology; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D009929:Organ Size; D047495:PPAR gamma / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013230:Stearoyl-CoA Desaturase / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D014280:Triglycerides / Q000032:analysis
chemical_list: D020738:Leptin; D047495:PPAR gamma; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase
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