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.
| Original language | English |
|---|---|
| Pages (from-to) | 3393-3411 |
| Number of pages | 19 |
| Journal | FASEB Journal |
| Volume | 26 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2012 |
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Keywords
- Glucose uptake
- High-fat diet
- Lipolysis
- PI3K/Akt and AMP-activated protein kinase
- Sirtuin 1
ASJC Scopus subject areas
- Biochemistry
- Biotechnology
- Genetics
- Molecular Biology
Cite this
Obestatin regulates adipocyte function and protects against diet-induced insulin resistance and inflammation. / Granata, Riccarda; Gallo, Davide; Luque, Raul M.; Baragli, Alessandra; Scarlatti, Francesca; Grande, Cristina; Gesmundo, Iacopo; Córdoba-Chacón, Jose; Bergandi, Loredana; Settanni, Fabio; Togliatto, Gabriele; Volante, Marco; Garetto, Stefano; Annunziata, Marta; Chanclón, Belén; Gargantini, Eleonora; Rocchietto, Stefano; Matera, Lina; Datta, Giacomo; Morino, Mario; Brizzi, Maria Felice; Ong, Huy; Camussi, Giovanni; Castaño, Justo P.; Papotti, Mauro; Ghigo, Ezio.
In: FASEB Journal, Vol. 26, No. 8, 08.2012, p. 3393-3411.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Obestatin regulates adipocyte function and protects against diet-induced insulin resistance and inflammation
AU - Granata, Riccarda
AU - Gallo, Davide
AU - Luque, Raul M.
AU - Baragli, Alessandra
AU - Scarlatti, Francesca
AU - Grande, Cristina
AU - Gesmundo, Iacopo
AU - Córdoba-Chacón, Jose
AU - Bergandi, Loredana
AU - Settanni, Fabio
AU - Togliatto, Gabriele
AU - Volante, Marco
AU - Garetto, Stefano
AU - Annunziata, Marta
AU - Chanclón, Belén
AU - Gargantini, Eleonora
AU - Rocchietto, Stefano
AU - Matera, Lina
AU - Datta, Giacomo
AU - Morino, Mario
AU - Brizzi, Maria Felice
AU - Ong, Huy
AU - Camussi, Giovanni
AU - Castaño, Justo P.
AU - Papotti, Mauro
AU - Ghigo, Ezio
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - Glucose uptake
KW - High-fat diet
KW - Lipolysis
KW - PI3K/Akt and AMP-activated protein kinase
KW - Sirtuin 1
UR - http://www.scopus.com/inward/record.url?scp=84864768395&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864768395&partnerID=8YFLogxK
U2 - 10.1096/fj.11-201343
DO - 10.1096/fj.11-201343
M3 - Article
C2 - 22601779
AN - SCOPUS:84864768395
VL - 26
SP - 3393
EP - 3411
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 8
ER -