title: Obestatin regulates adipocyte function and protects against diet-induced insulin resistance and inflammation.
abstract: The metabolic actions of the ghrelin gene-derived peptide obestatin are still unclear. We investigated obestatin effects in vitro, on adipocyte function, and in vivo, on insulin resistance and inflammation in mice fed a high-fat diet (HFD). Obestatin effects on apoptosis, differentiation, lipolysis, and glucose uptake were determined in vitro in mouse 3T3-L1 and in human subcutaneous (hSC) and omental (hOM) adipocytes. In vivo, the influence of obestatin on glucose metabolism was assessed in mice fed an HFD for 8 wk. 3T3-L1, hSC, and hOM preadipocytes and adipocytes secreted obestatin and showed specific binding for the hormone. Obestatin prevented apoptosis in 3T3-L1 preadipocytes by increasing phosphoinositide 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK)1/2 signaling. In both mice and human adipocytes, obestatin inhibited isoproterenol-induced lipolysis, promoted AMP-activated protein kinase phosphorylation, induced adiponectin, and reduced leptin secretion. Obestatin also enhanced glucose uptake in either the absence or presence of insulin, promoted GLUT4 translocation, and increased Akt phosphorylation and sirtuin 1 (SIRT1) protein expression. Inhibition of SIRT1 by small interfering RNA reduced obestatin-induced glucose uptake. In HFD-fed mice, obestatin reduced insulin resistance, increased insulin secretion from pancreatic islets, and reduced adipocyte apoptosis and inflammation in metabolic tissues. These results provide evidence of a novel role for obestatin in adipocyte function and glucose metabolism and suggest potential therapeutic perspectives in insulin resistance and metabolic dysfunctions.
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, Department of Internal Medicine, University of Turin, Corso Dogliotti 14-10126 Turin, Italy. riccarda.granata@unito.it
authors.forename: Riccarda
authors.initials: R
authors.lastname: Granata
authors.forename: Davide
authors.initials: D
authors.lastname: Gallo
authors.forename: Raul M
authors.initials: RM
authors.lastname: Luque
authors.forename: Alessandra
authors.initials: A
authors.lastname: Baragli
authors.forename: Francesca
authors.initials: F
authors.lastname: Scarlatti
authors.forename: Cristina
authors.initials: C
authors.lastname: Grande
authors.forename: Iacopo
authors.initials: I
authors.lastname: Gesmundo
authors.forename: Jose
authors.initials: J
authors.lastname: Córdoba-Chacón
authors.forename: Loredana
authors.initials: L
authors.lastname: Bergandi
authors.forename: Fabio
authors.initials: F
authors.lastname: Settanni
authors.forename: Gabriele
authors.initials: G
authors.lastname: Togliatto
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.forename: Stefano
authors.initials: S
authors.lastname: Garetto
authors.forename: Marta
authors.initials: M
authors.lastname: Annunziata
authors.forename: Belén
authors.initials: B
authors.lastname: Chanclón
authors.forename: Eleonora
authors.initials: E
authors.lastname: Gargantini
authors.forename: Stefano
authors.initials: S
authors.lastname: Rocchietto
authors.forename: Lina
authors.initials: L
authors.lastname: Matera
authors.forename: Giacomo
authors.initials: G
authors.lastname: Datta
authors.forename: Mario
authors.initials: M
authors.lastname: Morino
authors.forename: Maria Felice
authors.initials: MF
authors.lastname: Brizzi
authors.forename: Huy
authors.initials: H
authors.lastname: Ong
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
authors.forename: Justo P
authors.initials: JP
authors.lastname: Castaño
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059305:Diet, High-Fat; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D054439:Ghrelin / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000378:metabolism; D020738:Leptin; D008066:Lipolysis / Q000187:drug effects; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D052242:Adiponectin; D054439:Ghrelin; D051275:Glucose Transporter Type 4; D020738:Leptin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose