Central leptin signaling is required to normalize myocardial fatty acid oxidation rates in caloric-restricted ob/ob mice. Diabetes 60: 1424–1434. doi

OBJECTIVE—ob/ob and db/db mice manifest myocardial hyper-trophy, insulin resistance, altered substrate utilization, mitochon-drial dysfunction, and lipid accumulation. This study was designed to determine the contribution of central and peripheral leptin sig-naling to myocardial metabolism and function in ob/ob and db/db mice in the absence of diabetes and morbid obesity. RESEARCH DESIGN AND METHODS—Male ob/ob mice (4 weeks old) were caloric restricted by pair feeding to a leptin-treated ob/ob group. In addition to determining glucose toler-ance 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 intraperito-neal injection or intracerebroventricular infusion could normalize myocardial palmitate oxidation in caloric-restricted ob/ob mous