title: Long-term high-fat diet-induced obesity decreases the cardiac leptin receptor without apparent lipotoxicity.
abstract: OBJECTIVE
  Leptin resistance has been associated with cardiac lipotoxicity; however, whether leptin resistance is a risk factor associated with cardiac lipotoxicity at different time points in diet-induced obesity is unclear. The objective of this study was to evaluate this relationship.
  
  
  METHODS
  Male Wistar rats were fed a normal chow diet (12% from fat) or a high-fat diet (49% from fat) for 15 and 45 weeks, respectively. The adiposity index, body weight and co-morbidities were evaluated. Heart lipotoxicity was assessed by analyzing cardiac function and morphological changes as well as cardiac triglyceride, ceramide and lipid hydroperoxide accumulations. Cardiac apoptosis was examined using the TUNEL method. Leptin function was determined by examining plasma leptin levels, cardiac leptin receptors (OB-R) and related phosphorylations of AMP-activated kinase protein (AMPK) and Acetyl CoA carboxylase (ACC).
  
  
  RESULTS
  The diet-induced obesity was characterized by an elevated adiposity index, body weight and leptin levels at both 15 and 45 weeks. There was no difference between groups in the cardiac triglyceride or lipid hydroperoxide levels. Interestingly, ceramide levels decreased in obese animals in both experimental periods. The cardiac morphological and functional parameters were not altered. Although down-regulation of OB-R has occurred in chronic obesity, it did not adversely affect AMPK or ACC phosphorylation.
  
  
  CONCLUSIONS
  The development of obesity via long-term feeding of a high-fat diet to rats does not result in cardiac lipotoxicity but promotes the down-regulation of OB-R. However, this does not result in altered levels of AMPK or ACC phosphorylations in this animal model.
authors: Department of Medicine Clinical, Botucatu School of Medicine, São Paulo State University (UNESP), Brazil. nascimentoaf@yahoo.com.br
authors: André F
authors: AF
authors: Nascimento
authors: Renata A M
authors: RA
authors: Luvizotto
authors: André S
authors: AS
authors: Leopoldo
authors: Ana P
authors: AP
authors: Lima-Leopoldo
authors: Fábio R
authors: FR
authors: Seiva
authors: Luís A
authors: LA
authors: Justulin
authors: Maeli Dal Pai
authors: MD
authors: Silva
authors: Katashi
authors: K
authors: Okoshi
authors: Xiang-Dong
authors: XD
authors: Wang
authors: Antonio C
authors: AC
authors: Cicogna
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D050154:Adiposity; D000818:Animals; D017209:Apoptosis; D002518:Ceramides / Q000378:metabolism; D004041:Dietary Fats / Q000633:toxicity*; D004195:Disease Models, Animal; D015536:Down-Regulation; D020287:In Situ Nick-End Labeling; D020738:Leptin / Q000097:blood*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002518:Ceramides; D004041:Dietary Fats; D020738:Leptin; D008054:Lipid Peroxides; D054411:Receptors, Leptin; D014280:Triglycerides; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase