The metabolic actions of the ghrelin genederived 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.

Obestatin regulates adipocyte function and protects against diet-induced insulin resistance and inflammation.

GRANATA, Riccarda;GALLO, DAVIDE;BARAGLI, ALESSANDRA;SCARLATTI, FRANCESCA;GRANDE, CRISTINA;GESMUNDO, IACOPO;BERGANDI, Loredana;SETTANNI, Fabio;TOGLIATTO, Gabriele Maria;VOLANTE, Marco;GARETTO, STEFANO;ANNUNZIATA, Marta;GARGANTINI, ELEONORA;ROCCHIETTO, STEFANO;MATERA, Lina;MORINO, Mario;BRIZZI, Maria Felice;CAMUSSI, Giovanni;PAPOTTI, Mauro Giulio;GHIGO, Ezio
2012-01-01

Abstract

The metabolic actions of the ghrelin genederived 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.
2012
26
8
3393
3411
http://www.fasebj.org/content/early/2012/05/17/fj.11-201343.long
lipolysis glucose uptake PI3K/Akt and AMPactivated protein kinase sirtuin 1 high-fat diet; obestatin
Granata R; Gallo D; Luque RM; Baragli A; Scarlatti F; Grande C; Gesmundo I; Córdoba-Chacón J; Bergandi L; Settanni F; Togliatto G; Volante M; Garetto S; Annunziata M; Chanclón B; Gargantini E; Rocchietto S; Matera L; Datta G; Morino M; MF Brizzi ; Ong H; Camussi G; Castaño JP; Papotti M; Ghigo E.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/103505
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