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Obestatin regulates adipocyte function and protects against diet‐induced insulin resistance and inflammation
Author(s) -
Granata Riccarda,
Gallo Davide,
Luque Raul M.,
Baragli Alessandra,
Scarlatti Francesca,
Grande Cristina,
Gesmundo Iacopo,
CórdobaChacón 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
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-201343
Subject(s) - obestatin , medicine , endocrinology , adipocyte , insulin resistance , protein kinase b , glut4 , glucose uptake , insulin , lipolysis , biology , ghrelin , adipose tissue , signal transduction , hormone , microbiology and biotechnology
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.—Granata, R., Gallo, D., Luque, R. M., 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., Brizzi, M. F., Ong, H., Camussi, G., Castaño, J. P., Papotti, M., Ghigo, E. Obestatin regulates adipocyte function and protects against diet‐induced insulin resistance and inflammation. FASEB J. 26, 3393–3411 (2012). www.fasebj.org