Impaired Activation of Phosphatidylinositol 3-Kinase by Leptin is a Novel Mechanism of Hepatic Leptin Resistance in NAFLD

Background/Aims: The aim of this study was to detect the levels of leptin in serum and the expression of leptin, obesity receptor (OB-R), phosphatidylinositol 3-Kinase (p85) (PI3-K p85) and phospho-Akt-kinase (Akt) in non-alcoholic fatty liver disease (NAFLD). Methodology: The expressions of leptin, OB-R and. PI3-K/Akt kinase pathway were examined by immunohistochemistry. The level of leptin in serum was measured by radioimmunoassay. Results: In agreement with significantly elevated serum leptin levels in NAFLD patients (p<0.05), expression of leptin, OB-R and PI3-K (p85) was significant higher in NAFLD) patients (p<0.05) compared with the control patients. In contrast, expression of Akt was significantly down-regulated in the NAFLD patients (p<0.05). Moreover, PI3-K (p85) expression was significantly, positively correlated with leptin (r= 0.365, p<0.05) but negatively correlated with Akt (r=-0.854, p<0.01). Conclusions: Leptin may be involved in NAFLD pathogenesis by activating the PI3-K/Akt kinase pathway via OB-R and the defective leptin activation of PI3-K is a novel mechanism of leptin resistance in NAFLD.