Central Leptin Signaling Is Required to Normalize Myocardial Fatty Acid
Oxidation Rates in Caloric-Restricted ob/ob Mice.
Authors Sloan C, Tuinei J, Nemetz K, Frandsen J, Soto J, Wride N, Sempokuya T, Alegria
L, Bugger H, Abel ED
Submitted By E. Dale Abel on 5/2/2011
Status Published
Journal Diabetes
Year 2011
Date Published 5/1/2011
Volume : Pages 60 : 1424 - 1434
PubMed Reference 21441440
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. RESEARCH DESIGN
AND 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-a ligands to the heart.

Investigators with authorship
E. Dale AbelUniversity of Iowa