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



8 patients with T2DM (Age: 56 ± 11; BMI: 28 ± 3.5 kg/m(2); 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 (1)H-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.



Our 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.
Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, Vienna, Austria.
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Wolf
Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, Vienna, Austria. Electronic address: yvonne.winhofer@meduniwien.ac.at.
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Winhofer
Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, Vienna, Austria; Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Centre of Excellence - High Field MR, Vienna, Austria.
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Krssak
Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, Vienna, Austria.
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S
Smajis
Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, Vienna, Austria.
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J
Harreiter
Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, Vienna, Austria.
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Kosi-Trebotic
Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, Vienna, Austria.
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Fürnsinn
Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, Vienna, Austria; Metabolic Unit, Institute of Biomedical Engineering, National Research Council, Padova, Italy; Medical Direction, Specialized Hospital Complex Agathenhof, A-9322 Micheldorf, Austria.
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Anderwald
Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, Vienna, Austria.
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S
Baumgartner-Parzer
Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Centre of Excellence - High Field MR, Vienna, Austria.
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Trattnig
Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, Vienna, Austria.
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A
Luger
Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, Vienna, Austria.
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Krebs
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000368:Aged; D001317:Austria; D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D058065:Diabetic Cardiomyopathies / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D015536:Down-Regulation; D004734:Energy Metabolism / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008066:Lipolysis / Q000187:drug effects*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D016037:Single-Blind Method; D013318:Stroke Volume / Q000187:drug effects; D013599:Systole; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*
D015415:Biomarkers; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D011719:Pyrazines; C027696:acipimox
Cardiac steatosis; Diabetic cardiomyopathy; Ectopic lipids; Metabolic inflexibility