Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Sloan, C; Tuinei, J; Nemetz, K; Frandsen, J; Soto, J; Wride, N; Sempokuya, T; Alegria, L; Bugger, H; Abel, ED.
Central leptin signaling is required to normalize myocardial fatty acid oxidation rates in caloric-restricted ob/ob mice.
Diabetes. 2011; 60(5): 1424-1434.
Doi: 10.2337/db10-1106
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- Co-Autor*innen der Med Uni Graz
- Bugger Heiko Matthias
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- Abstract:
- 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. 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. 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. 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adiponectin - blood
- Animals -
- Body Composition - drug effects
- Caloric Restriction -
- Fatty Acids - blood
- Fatty Acids - metabolism
- Glucose Tolerance Test -
- Heart - drug effects
- Injections, Intraperitoneal -
- Leptin - administration & dosage
- Leptin - blood
- Leptin - pharmacology
- Male -
- Mice -
- Mice, Obese -
- Microscopy, Electron -
- Mitochondria - drug effects
- Mitochondria - metabolism
- Mitochondria - ultrastructure
- Myocardium - metabolism
- Myocardium - ultrastructure
- Oxidation-Reduction - drug effects
- Palmitic Acids - metabolism
- Polymerase Chain Reaction -
- Signal Transduction -
- Triglycerides - blood
- Triglycerides - metabolism