Diurnal variations in the responsiveness of cardiac and skeletal muscle to fatty acids

• Published in: American journal of physiology: endocrinology and metabolism Vol. 287; no. 5; pp. E878 - E887
• Main Authors: Stavinoha, Melissa A, RaySpellicy, Joseph W, Hart-Sailors, Mary L, Mersmann, Harry J, Bray, Molly S, Young, Martin E
• Format: Journal Article
• Language: English
• Published: United States 01.11.2004
• Subjects: Animals; Circadian Rhythm - physiology; Diabetes Mellitus, Experimental - physiopathology; Dietary Fats - blood; Disease Models, Animal; Enzyme Induction - physiology; Fatty Acids, Nonesterified - blood; Gene Expression Regulation; Male; Muscle, Skeletal - metabolism; Myocardium - metabolism; PPAR alpha - metabolism; Protein Kinases - biosynthesis; Protein Kinases - genetics; Protein Kinases - metabolism; Rats; Rats, Wistar; RNA - analysis
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00189.2004

1 Brown Foundation Institute of Molecular Medicine and 2 School of Public Health, Human Genetics Center, University of Texas Health Science Center at Houston; and 3 United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030 Submitted 30 April 2004 ; accepted in final form 26 July 2004 Cardiac and skeletal muscle both respond to elevated fatty acid availability by increasing fatty acid oxidation, an effect mediated in large part by peroxisome proliferator-activated receptor- (PPAR ). We hypothesized that cardiac and skeletal muscle alter their responsiveness to fatty acids over the course of the day, allowing optimal adaptation when availability of this substrate increases. In the current study, pyruvate dehydrogenase kinase 4 ( pdk4 ) was utilized as a representative PPAR -regulated gene. Opposing diurnal variations in pdk4 expression were observed in cardiac and skeletal muscle isolated from the ad libitum-fed rat; pdk4 expression peaked in the middle of the dark and light phases, respectively. Elevation of circulating fatty acid levels by high-fat feeding, fasting, and streptozotocin-induced diabetes increased pdk4 expression in both heart and soleus muscle. Highest levels of induction were observed during the dark phase, regardless of muscle type or intervention. Specific activation of PPAR with WY-14643 rapidly induced pdk4 expression in heart and soleus muscle. Highest levels of induction were again observed during the dark phase. The same pattern of induction was observed for the PPAR -regulated genes malonyl-CoA decarboxylase and uncoupling protein 3. Investigation into the potential mechanism(s) for these observations exposed a coordinated upregulation of transcriptional activators of the PPAR system during the night, with a concomitant downregulation of transcriptional repressors in both muscle types. In conclusion, responsiveness of cardiac and skeletal muscle to fatty acids exhibits a marked diurnal variation. These observations have important physiological and pathophysiological implications, ranging from experimental design to pharmacological treatment of patients. diabetes; fasting; high-fat feeding; peroxisome proliferator-activated receptor- ; pyruvate dehydrogenase kinase 4 Address for reprint requests and other correspondence: M. E. Young, Brown Foundation Institute of Molecular Medicine, Univ. of Texas Health Science Center at Houston, 2121 W. Holcombe Blvd., IBT 1011B, Houston, TX 77030 (E-mail: Martin.E.Young{at}uth.tmc.edu )