Previous studies have reported that high fat feeding in mild to moderate
heart failure (HF) results in the preservation of contractile function. Recent evidence has suggested that preventing the switch from
fatty acid to
glucose metabolism in HF may ameliorate dysfunction, and
insulin resistance is one potential mechanism for regulating substrate utilization. This study was designed to determine whether peripheral and myocardial
insulin resistance exists with HF and/or a high-fat diet and whether myocardial
insulin signaling was altered accordingly. Rats underwent coronary artery
ligation (HF) or
sham surgery and were randomized to normal chow (NC; 14% kcal from fat) or a high-fat diet (SAT; 60% kcal from fat) for 8 wk. HF + SAT animals showed preserved systolic (+dP/dt and
stroke work) and diastolic (-dP/dt and time constant of relaxation) function compared with HF + NC animals.
Glucose tolerance tests revealed peripheral
insulin resistance in
sham + SAT, HF + NC, and HF + SAT animals compared with
sham + NC animals. PET imaging confirmed myocardial
insulin resistance only in HF + SAT animals, with an uptake ratio of 2.3 ± 0.3 versus 4.6 ± 0.7, 4.3 ± 0.4, and 4.2 ± 0.6 in
sham + NC,
sham + SAT, and HF + NC animals, respectively; the myocardial
glucose utilization rate was similarly decreased in HF + SAT animals only. Western blot analysis of
insulin signaling
protein expression was indicative of cardiac
insulin resistance in HF + SAT animals. Specifically, alterations in Akt and
glycogen synthase kinase-3β
protein expression in HF + SAT animals compared with HF + NC animals may be involved in mediating myocardial
insulin resistance. In conclusion, HF animals fed a high-saturated fat exhibited preserved myocardial contractile function, peripheral and myocardial
insulin resistance, decreased myocardial
glucose utilization rates, and alterations in cardiac
insulin signaling. These results suggest that myocardial
insulin resistance may serve a cardioprotective function with high fat feeding in mild to moderate HF.