Figure 1. Increasing FAO attenuated HFD induced cardiomyopathy.

Con and ACC2 iKO mice were subjected to chow or HFD feeding for 24 weeks. (A) Representative immunoblots of heart lysates of p-ACC (Ser 79), ACC and GAPDH are shown. (B-C) Hearts were perfused with a buffer containing ¹³C labeled fatty acids, ¹³C labeled glucose, lactate, and insulin (mixed substrate). (B) Contribution of ¹³C labeled substrates to tricarboxylic acid (TCA) cycle was determined by ¹³C NMR spectroscopy in heart extracts. Relative contribution of fatty acids (FAs), glucose (GLC), and other unlabeled substrates (lactate, endogenous) (Unlabeled) is shown (*p<0.05 vs. Con/chow, #p<0.05 vs. Con/HFD, n=4–5). (C) Phosphocreatine to ATP (PCr/ATP) ratio was measured by ³¹P NMR spectroscopy in isolated perfused hearts (#p<0.05 vs. Con/HFD, n=4–5). (D) Cardiac triglyceride (TAG) content normalized to tissue weight (*p<0.05 vs. Con/chow, #p<0.05 vs. Con/HFD, n=6–8). (E-G) Left ventricular ejection fraction (LVEF), E’/A’ ratio and isovolumic relaxation time (IVRT) were measured by echocardiography (*p<0.05 vs. Con/chow, #p<0.05 vs. Con/HFD, n=6–8). (H) The left ventricle weight to tibia length (LV/TL) ratio of ACC2 iKO and Con mice under chow- or HFD-fed conditions (*p<0.05 vs. Con/chow, #p<0.05 vs. Con/HFD, n=4–6). (I) Representative wheat germ agglutinin (WGA) staining and quantification of cardiomyocyte cross-sectional area in indicated hearts after 24 weeks’ chow or HFD feeding (*p<0.05 vs. Con/chow, #p<0.05 vs. Con/HFD, n=4), Scale bar, 50μm. (J) Representative picric acid sirius red (PASR) staining and quantification of the percentage of fibrosis in indicated hearts after 24 weeks’ chow or HFD feeding (*p<0.05 vs. Con/chow, #p<0.05 vs. Con/HFD, n=4), Scale bar, 100μm.