Suppression of plasma free fatty acids reduces myocardial lipid content and systolic function in type 2 diabetes

Abstract

Background and AimType 2 diabetes (T2DM) is closely associated with the development of heart failure, which might be related with impaired substrate metabolism and accumulation of myocardial lipids (MYCL). The aim of this study was to investigate the impact of an acute pharmacological inhibition of adipose tissue lipolysis leading to reduced availability of circulating FFA on MYCL and heart function in T2DM. Methods and Results8 patients with T2DM (Age: 56 ± 11; BMI: 28 ± 3.5 kg/m2; HbA1c: 7.29 ± 0.88%) were investigated on two study days in random order. Following administration of Acipimox or Placebo MYCL and heart function were measured by 1H-magnetic-resonance-spectroscopy and tomography at baseline, at 2 and at 6 h. Acipimox reduced circulating FFA by −69% (p < 0.001), MYCL by −39 ± 41% (p < 0.001) as well as systolic heart function (Ejection Fraction (EF): −13 ± 8%, p = 0.025; Cardiac Index: −16 ± 15%, p = 0.063 compared to baseline). Changes in plasma FFA concentrations strongly correlated with changes in MYCL (r = 0.707; p = 0.002) and EF (r = 0.651; p = 0.006). Diastolic heart function remained unchanged. ConclusionsOur results indicate, that inhibition of adipose tissue lipolysis is associated with a rapid depletion of MYCL-stores and reduced systolic heart function in T2DM. These changes were comparable to those previously found in insulin sensitive controls. MYCL thus likely serve as a readily available energy source to cope with short-time changes in FFA availability.