title: PI3K signaling in the pathogenesis of obesity: The cause and the cure.
abstract: With the steady rise in the incidence of obesity and its associated comorbidities, in the last decades research aimed at understanding molecular mechanisms that control body weight has gained new interest. Fat gain is frequently associated with chronic adipose tissue inflammation and with peripheral as well as central metabolic derangements, resulting in an impaired hypothalamic regulation of energy homeostasis. Recent attention has focused on the role of phosphatidylinositol 3-kinase (PI3K) in both immune and metabolic response pathways, being involved in the pathophysiology of obesity and its associated metabolic diseases. In this review, we focus on distinct PI3K isoforms, especially class I PI3Ks, mediating inflammatory cells recruitment to the enlarged fat as well as intracellular responses to key hormonal regulators of fat storage, both in adipocytes and in the central nervous system. This integrated view of PI3K functions may ultimately help to develop new therapeutic interventions for the treatment of obesity.
authors.affiliation: Molecular Biotechnology Center, University of Torino, Torino, Italy; Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Beretta
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
authors.affiliation: Molecular Biotechnology Center, University of Torino, Torino, Italy. Electronic address: emilio.hirsch@unito.it.
authors.forename: Emilio
authors.initials: E
authors.lastname: Hirsch
mesh_terms: D017667:Adipocytes / Q000276:immunology / Q000473:pathology; D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007031:Hypothalamus / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007113:Immunity, Innate; D007249:Inflammation; D007333:Insulin Resistance; D020738:Leptin / Q000235:genetics / Q000276:immunology; D009765:Obesity / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D020738:Leptin; C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4; D058534:Class I Phosphatidylinositol 3-Kinases
keywords: Energy homeostasis; Inflammation; Insulin resistance; Leptin; Obesity; PI3Ks