Obestatin as a regulator of adipocyte metabolism and adipogenesis

The role of obestatin, a 23‐amino‐acid peptide encoded by the ghrelin gene, on the control of the metabolism of pre‐adipocyte and adipocytes as well as on adipogenesis was determined. For in vitro assays, pre‐adipocyte and adipocyte 3T3‐L1 cells were used to assess the obestatin effect on cell metab...

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Published in:Journal of cellular and molecular medicine 2011-09, Vol.15 (9), p.1927-1940
Main Authors: Gurriarán‐Rodríguez, Uxía, Al‐Massadi, Omar, Roca‐Rivada, Arturo, Crujeiras, Ana Belén, Gallego, Rosalía, Pardo, Maria, Seoane, Luisa Maria, Pazos, Yolanda, Casanueva, Felipe F., Camiña, Jesús P.
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Adenylate Kinase - metabolism
adipocyte metabolism
Adipocytes
Adipocytes - drug effects
Adipocytes - enzymology
Adipocytes - metabolism
Adipogenesis
Adipogenesis - drug effects
Adipose tissue
Adipose Tissue, White - drug effects
Adipose Tissue, White - enzymology
Akt
AKT protein
Animals
Antibodies
Autocrine Communication - drug effects
Autocrine signalling
Blotting, Western
Body fat
CD36 antigen
Cell differentiation
Cell Membrane - drug effects
Cell Membrane - metabolism
Enzyme Activation - drug effects
Fatty Acid Transport Proteins - metabolism
Gene expression
Ghrelin
Ghrelin - metabolism
Ghrelin - pharmacology
Glucose - metabolism
Glucose Transporter Type 1 - metabolism
Glucose Transporter Type 4 - metabolism
Homogenization
Insulin
Lipids
Male
Metabolic syndrome
Metabolism
Mice
Paracrine Communication - drug effects
Paracrine signalling
Penicillin
Peptides
Phosphatase
Phosphorylation
Phosphorylation - drug effects
Protein Transport - drug effects
Proto-Oncogene Proteins c-akt - metabolism
Rats
Rats, Sprague-Dawley
siRNA
Time Factors
TOR protein
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Summary:The role of obestatin, a 23‐amino‐acid peptide encoded by the ghrelin gene, on the control of the metabolism of pre‐adipocyte and adipocytes as well as on adipogenesis was determined. For in vitro assays, pre‐adipocyte and adipocyte 3T3‐L1 cells were used to assess the obestatin effect on cell metabolism and adipogenesis based on the regulation of the key enzymatic nodes, Akt and AMPK and their downstream targets. For in vivo assays, white adipose tissue (WAT) was obtained from male rats under continuous subcutaneous infusion of obestatin. Obestatin activated Akt and its downstream targets, GSK3α/β, mTOR and S6K1, in 3T3‐L1 adipocyte cells. Simultaneously, obestatin inactivated AMPK in this cell model. In keeping with this, ACC phosphorylation was also decreased. This fact was confirmed in vivo in white adipose tissue (omental, subcutaneous and gonadal) obtained from male rats under continuous sc infusion of obestatin (24 and 72 hrs). The relevance of obestatin as regulator of adipocyte metabolism was supported by AS160 phosphorylation, GLUT4 translocation and augment of glucose uptake in 3T3‐L1 adipocyte cells. In contrast, obestatin failed to modify translocation of fatty acid transporters, FATP1, FATP4 and FAT/CD36, to plasma membrane. Obestatin treatment in combination with IBMX and DEX showed to regulate the expression of C/EBPα, C/EBPβ, C/EBPδ and PPARγ promoting adipogenesis. Remarkable, preproghrelin expression, and thus obestatin expression, increased during adipogenesis being sustained throughout terminal differentiation. Neutralization of endogenous obestatin secreted by 3T3‐L1 cells by anti‐obestatin antibody decreased adipocyte differentiation. Furthermore, knockdown experiments by preproghrelin siRNA supported that obestatin contributes to adipogenesis. In summary, obestatin promotes adipogenesis in an autocrine/paracrine manner, being a regulator of adipocyte metabolism. These data point to a putative role in the pathogenesis of metabolic syndrome.
ISSN:1582-1838
1582-4934
DOI:10.1111/j.1582-4934.2010.01192.x