title: Central leptin signaling is required to normalize myocardial fatty acid oxidation rates in caloric-restricted ob/ob mice.
abstract: OBJECTIVE
  ob/ob and db/db mice manifest myocardial hypertrophy, insulin resistance, altered substrate utilization, mitochondrial dysfunction, and lipid accumulation. This study was designed to determine the contribution of central and peripheral leptin signaling to myocardial metabolism and function in ob/ob and db/db mice in the absence of diabetes and morbid obesity.
  
  
  METHODS
  Male ob/ob mice (aged 4 weeks) were caloric restricted by pairfeeding to a leptin-treated ob/ob group. In addition to determining glucose tolerance and circulating lipid concentrations, myocardial substrate metabolism and mitochondrial function were determined in saponin-permeabilized cardiac fibers. Second, experiments were performed to determine whether leptin treatment by intraperitoneal injection or intracerebroventricular infusion could normalize myocardial palmitate oxidation in caloric-restricted ob/ob mouse hearts.
  
  
  RESULTS
  Despite normalizing body weight and glucose tolerance, fat mass and circulating lipid levels remained increased in caloric-restricted ob/ob animals. Palmitate oxidation remained elevated in caloric-restricted ob/ob hearts and was normalized by intraperitoneal or intracerebroventricular leptin. Intraperitoneal and intracerebroventricular treatment also normalized circulating free fatty acid levels, myocardial fatty acid oxidation gene expression, and myocardial insulin sensitivity.
  
  
  CONCLUSIONS
  These data suggest that impaired hypothalamic leptin signaling is sufficient to increase myocardial fatty acid oxidation by increasing delivery of free fatty acid substrates and peroxisome proliferator-activated receptor-α ligands to the heart.
authors: Program in Molecular Medicine, University of Utah, Salt Lake City, Utah, USA.
authors: Crystal
authors: C
authors: Sloan
authors: Joseph
authors: J
authors: Tuinei
authors: Katherine
authors: K
authors: Nemetz
authors: Jonathan
authors: J
authors: Frandsen
authors: Jamie
authors: J
authors: Soto
authors: Noah
authors: N
authors: Wride
authors: Tomoki
authors: T
authors: Sempokuya
authors: Luis
authors: L
authors: Alegria
authors: Heiko
authors: H
authors: Bugger
authors: E Dale
authors: ED
authors: Abel
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D031204:Caloric Restriction; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006321:Heart / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D020738:Leptin / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010084:Oxidation-Reduction / Q000187:drug effects; D010169:Palmitic Acids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D052242:Adiponectin; D005227:Fatty Acids; D020738:Leptin; D010169:Palmitic Acids; D014280:Triglycerides