title: Impaired activation of phosphatidylinositol 3-kinase by leptin is a novel mechanism of hepatic leptin resistance in NAFLD.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
authors.affiliation: Department of Gastroenterology, The Central Hospital of Wuhan, Wuhan, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Huang
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Yuan
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Fan
authors.forename: He-Sheng
authors.initials: HS
authors.lastname: Luo
authors.forename: Yue-Hong
authors.initials: YH
authors.lastname: Yang
mesh_terms: D005234:Fatty Liver / Q000097:blood*; D006801:Humans; D007124:Immunoenzyme Techniques; D020738:Leptin / Q000097:blood*; D016014:Linear Models; D065626:Non-alcoholic Fatty Liver Disease; D051058:Oncogene Protein v-akt / Q000097:blood; D058539:Phosphatidylinositol 3-Kinase / Q000097:blood*; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism; D054411:Receptors, Leptin / Q000097:blood; D015398:Signal Transduction
chemical_list: C515448:LEPR protein, human; D020738:Leptin; C121623:PSMF1 protein, human; D011506:Proteins; D054411:Receptors, Leptin; D058539:Phosphatidylinositol 3-Kinase; D051058:Oncogene Protein v-akt; D046988:Proteasome Endopeptidase Complex