title: Effects of acute and one-week fatty acid lowering on cardiac function and insulin sensitivity in relation with myocardial and muscle fat and adiponectin levels.
abstract: OBJECTIVE
  We tested the hypothesis that a persistent reduction in free fatty acid (FFA) levels improves cardiac function and systemic insulin sensitivity via a reduction in the myocardial and skeletal muscle adiposities and a modulation in adipokine release.
  
  
  METHODS
  Study subjects (body mass index 22-30 kg/m(2), 57 ± 3 yr old) underwent magnetic resonance imaging and spectroscopy to measure the cardiac function and the amounts of fat inside and around the myocardium and skeletal muscle, before (n = 10) and after acute (n = 8) and 1 wk (n = 7, one excluded from analysis) lowering of circulating FFA by acipimox. Circulating adipokines (leptin, adiponectin, resistin, TNFα, IL-6, IL-8, plasminogen activator inhibitor-I, macrophage chemoattractant protein-1) were measured.
  
  
  RESULTS
  The ejection fraction (62 ± 2 vs. 56 ± 1%, P = 0.0035), cardiac output (6.6 ± 0.3 vs. 5.5 ± 0.2 liters/min, P = 0.0018), and forward work (708 ± 49 vs. 539 ± 44 mm Hg × liters/min, P = 0.018) were significantly lower after 1 wk of FFA lowering. In the six subjects undergoing all sessions, the stroke and end-diastolic volumes were also reduced, insulin sensitivity was increased by 33%, and adiponectinemia was decreased (-26%, P = 0.03). No change in intracellular cardiac and skeletal muscle triglyceride levels was observed. Metabolic changes correlated with the lowering of FFA. The reduction in cardiac function was related with changes in glycemia and insulin sensitivity, whereas the deflection in left ventricular work was correlated with the decline in FFA, lipid, and blood pressure levels.
  
  
  CONCLUSIONS
  A 1-wk FFA depletion suppressed cardiac function and improved insulin sensitivity. Intracellular triglyceride deposits in the heart and skeletal muscle played no role in the observed changes. Our data show that FFA participate in the physiological regulation of adipokine levels.
authors: Turku PET Centre, University of Turku, FIN-20521 Turku, Finland.
authors: Hanna-Riikka
authors: HR
authors: Lehto
authors: Jussi
authors: J
authors: Pärkkä
authors: Ronald
authors: R
authors: Borra
authors: Helena
authors: H
authors: Tuunanen
authors: Virva
authors: V
authors: Lepomaki
authors: Riitta
authors: R
authors: Parkkola
authors: Juhani
authors: J
authors: Knuuti
authors: Pirjo
authors: P
authors: Nuutila
authors: Patricia
authors: P
authors: Iozzo
mesh_terms: D054392:Adipokines / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D000328:Adult; D000368:Aged; D005230:Fatty Acids, Nonesterified / Q000037:antagonists & inhibitors* / Q000097:blood*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006334:Heart Function Tests; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D054392:Adipokines; D052242:Adiponectin; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D011719:Pyrazines; C027696:acipimox