Turku PET Centre, University of Turku, FIN-20521 Turku, Finland.
J Clin Endocrinol Metab. 2012 Sep;97(9):3277-84. doi: 10.1210/jc.2012-1219. Epub 2012 Jul 3.
BACKGROUND/AIM: 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.
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.
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.
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.
背景/目的：我们检验了一个假设，即游离脂肪酸（FFA）水平的持续降低可通过减少心肌和骨骼肌脂肪含量以及调节脂肪因子的释放，改善心脏功能和全身胰岛素敏感性。
研究对象（体重指数 22-30kg/m²，57±3 岁）在接受磁共振成像和光谱检查以测量心脏功能和心肌和骨骼肌内外脂肪量之前（n=10）、之后（n=8）和 1 周（n=7，有 1 人从分析中排除），通过阿昔莫司降低循环 FFA。测量循环脂肪因子（瘦素、脂联素、抵抗素、TNFα、IL-6、IL-8、纤溶酶原激活物抑制剂-1、巨噬细胞趋化蛋白-1）。
在 FFA 降低 1 周后，射血分数（62±2%比 56±1%，P=0.0035）、心输出量（6.6±0.3 比 5.5±0.2 升/分钟，P=0.0018）和前功（708±49 比 539±44mmHg×升/分钟，P=0.018）显著降低。在进行所有 3 次检查的 6 名受试者中，心搏量和舒张末期容积也降低，胰岛素敏感性增加 33%，脂联素血症降低（-26%，P=0.03）。未观察到心肌和骨骼肌细胞内甘油三酯水平的变化。代谢变化与 FFA 的降低相关。心脏功能的降低与血糖和胰岛素敏感性的变化有关，而左心室功的偏转与 FFA、血脂和血压水平的下降相关。
FFA 消耗 1 周可抑制心脏功能并改善胰岛素敏感性。心脏和骨骼肌内的细胞内甘油三酯沉积在观察到的变化中不起作用。我们的数据表明 FFA 参与了脂肪因子水平的生理调节。
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