title: Deficiency of phosphoinositide 3-kinase enhancer protects mice from diet-induced obesity and insulin resistance.
abstract: OBJECTIVE
  Phosphoinositide 3-kinase enhancer A (PIKE-A) is a proto-oncogene that promotes tumor growth and transformation by enhancing Akt activity. However, the physiological functions of PIKE-A in peripheral tissues are unknown. Here, we describe the effect of PIKE deletion in mice and explore the role of PIKE-A in obesity development.
  
  
  METHODS
  Whole-body PIKE knockout mice were generated and subjected to high-fat-diet feeding for 20 weeks. The glucose tolerance, tissue-specific insulin sensitivity, adipocyte differentiation, and lipid oxidation status were determined. The molecular mechanism of PIKE in the insulin signaling pathway was also studied.
  
  
  RESULTS
  We show that PIKE-A regulates obesity development by modulating AMP-activated protein kinase (AMPK) phosphorylation. PIKE-A is important for insulin to suppress AMPK phosphorylation. The expression of PIKE-A is markedly increased in adipose tissue of obese mice, whereas depletion of PIKE-A inhibits adipocyte differentiation. PIKE knockout mice exhibit a prominent phenotype of lipoatrophy and are resistant to high-fat diet-induced obesity, liver steatosis, and diabetes. PIKE knockout mice also have augmented lipid oxidation, which is accompanied by enhanced AMPK phosphorylation in both muscle and adipose tissue. Moreover, insulin sensitivity is improved in PIKE-A-deficient muscle and fat, thus protecting the animals from diet-induced diabetes.
  
  
  CONCLUSIONS
  Our results suggest that PIKE-A is implicated in obesity and associated diabetes development by negatively regulating AMPK activity.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Chi Bun
authors.initials: CB
authors.lastname: Chan
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Jung
authors.forename: John Y
authors.initials: JY
authors.lastname: Jun
authors.forename: Hongbo R
authors.initials: HR
authors.lastname: Luo
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kim
authors.forename: Keqiang
authors.initials: K
authors.lastname: Ye
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D017667:Adipocytes / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation; D017931:DNA Primers; D004041:Dietary Fats / Q000008:administration & dosage*; D005091:Exons; D020558:GTP Phosphohydrolases / Q000172:deficiency* / Q000235:genetics; D015870:Gene Expression; D007333:Insulin Resistance / Q000235:genetics; D015227:Lipid Peroxidation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D009765:Obesity / Q000235:genetics / Q000517:prevention & control*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D012313:RNA / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D017931:DNA Primers; D004041:Dietary Fats; D009419:Nerve Tissue Proteins; D012313:RNA; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D020558:GTP Phosphohydrolases; C529781:PIKE protein, mouse