Altered hepatic lipid metabolism contributes to nonalcoholic fatty liver disease in leptin-deficient Ob/Ob Mice

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 co2) 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. © 2013 james w. perfield ii et al.