title: Ghrelin signaling in heart remodeling of adult obese mice.
abstract: Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), has been suggested to be associated to obesity, insulin secretion, cardiovascular growth and homeostasis. GHS-R has been found in most of the tissues, and among the hormone action it is included the regulation of heart energy metabolism. Therefore, hypernutrition during early life leads to obesity, induces cardiac hypertrophy, compromises myocardial function, inducing heart failure in adulthood. We examined ghrelin signaling process in cardiac remodeling in these obese adult mice. The cardiomyocytes (cmy) of left ventricle were analyzed by light microscopy and stereology, content and phosphorilation of cardiac proteins: ghrelin receptor (growth hormone secretagogue receptor 1a, GHSR-1a), protein kinase B (AKT and pAKT), phosphatidil inositol 3 kinase (PI3K), AMP-activated protein kinase (AMPK and pAMPK) and actin were achieved by Western blotting. GHSR-1a gene expression was analyzed by Real Time-PCR. We observed hyperglycemia and higher liver and visceral fat weight in obese when compared to control group. Obese mice presented a marked increase in heart weight/tibia length, indicating an enlarged heart size or a remodeling process. Obese mice had increased GHSR-1a content and expression in the heart associated to PI3K content and increased AKT content and phosphorylation. In contrast, AMPK content and phosphorylation in heart was not different between experimental groups. Ghrelin plasma levels in obese group were decreased when compared to control group. Our data suggest that remodeled myocardial in adult obese mice overnourished in early life are associated with higher phosphorylation of GHSR-1a, PI3K and AKT but not with AMPK.
authors.affiliation: Department of Physiology, Institute of Biology, State University of Rio de Janeiro, Avenue 28 de setembro, 87 Fundos, 5 andar, Vila Isabel, Rio de Janeiro 20551-030, Brazil.
authors.forename: Glauciane
authors.initials: G
authors.lastname: Lacerda-Miranda
authors.forename: Vivian M
authors.initials: VM
authors.lastname: Soares
authors.forename: Anatalia K G
authors.initials: AK
authors.lastname: Vieira
authors.forename: Juliana G
authors.initials: JG
authors.lastname: Lessa
authors.forename: Alessandra C S
authors.initials: AC
authors.lastname: Rodrigues-Cunha
authors.forename: Erika
authors.initials: E
authors.lastname: Cortez
authors.forename: Erica P
authors.initials: EP
authors.lastname: Garcia-Souza
authors.forename: Anibal S
authors.initials: AS
authors.lastname: Moura
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D000833:Animals, Suckling; D001786:Blood Glucose; D048429:Cell Size; D005260:Female; D015870:Gene Expression; D054439:Ghrelin / Q000097:blood* / Q000502:physiology; D006352:Heart Ventricles / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D050152:Intra-Abdominal Fat / Q000473:pathology; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000502:physiology; D009765:Obesity / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism*; D020257:Ventricular Remodeling; D015430:Weight Gain
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D054440:Receptors, Ghrelin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000263:Adenylate Kinase