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• W2002783706 abstract "Background: Derangements in skeletal muscle (SM) metabolism and function develop in heart failure (HF). SM metabolism switches to preferential utilization of glycolytic substrates reflected by an increased number of fast-twitch SM fibers. Further, insulin resistance and loss of muscle mass contribute to exercise intolerance in HF. We analyzed metabolic gene expression patterns, triglyceride content and muscle fiber cross-sectional area (CSA) in order to characterize abnormalities of metabolism and atrophy in HF. Methods: Ligation of the left coronary artery (MI) or sham surgery was performed in C57BL/6 mice (8 wks, n = 5 per group). After 8 wks, echocardiography was performed and the animals sacrificed. Skeletal muscle (quadriceps) gene expression was assessed by qRT-PCR. Lipids were extracted by the Folch method and quantified with colorimetric enzymatic assays. Muscle fiber CSA was analyzed using ImageJ. Results: Echocardiography confirmed impaired cardiac function post-MI (fractional shortening: 23.7 ± 1.9% in MI vs 31.5 ± 0.8% in sham, p < 0.005). No differences were found in total body weight (BW) while heart weight/BW increased in the MI group. Muscle weight/BW was reduced in the MI group (p < 0.05 vs sham). GLUT4 mRNA was increased with concurrent decrease in PDK4 mRNA indicating an increase in glucose oxidation. Markers of lipid uptake and oxidation (PPARg, CPT1 and CD36) remained unchanged. Notably, ATGL, a lipolytic enzyme and PGC-1a, a critical regulator of oxidative muscle metabolism, showed decreased expression in the MI group. Muscle triglyceride content increased significantly (12.0 ± 0.64 mg/g vs 3.1 ± 1.22 mg/g in sham, p < 0.001) but levels of muscle free fatty acids were unchanged. Muscle fiber CSA was decreased (1542 ± 484 um2 vs 1713 ± 552 um2 in sham, p < 0.001). Conclusion: Our data demonstrate a distinct metabolic gene expression pattern with a shift towards increased glucose transport and oxidation, stable lipid uptake and oxidation, decreased lipolysis and increased triglyceride content in skeletal muscle of animals with left ventricular dysfunction. Our findings are consistent with preferential utilization of glucose for ATP generation. We hypothesize that abnormal intramuscular substrate utilization through accumulation of toxic lipid intermediates contributes to the development and progression of catabolic metabolism and muscle atrophy in HF." @default.
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• W2002783706 date "2010-08-01" @default.
• W2002783706 modified "2023-10-16" @default.
• W2002783706 title "Elevated Intramuscular Triglycerides Are Associated with Suppression of PDK4, Enhanced Glucose Oxidation and Muscle Fiber Atrophy in Animals with Chronic Left Ventricular Dysfunction" @default.
• W2002783706 doi "https://doi.org/10.1016/j.cardfail.2010.06.124" @default.
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