Intrinsic diurnal variations in cardiac metabolism and contractile function.
Diurnal variation of cardiac function in vivo has been attributed primarily to changes in factors such as sympathetic activity. No study has investigated previously the intrinsic properties of the heart throughout the day. We therefore investigated diurnal variations in metabolic flux and contractile function of the isolated working rat heart and how this related to circadian expression of metabolic genes. Contractile performance, carbohydrate oxidation, and oxygen consumption were greatest in the middle of the night, with little variation in fatty acid oxidation. The expression of all metabolic genes investigated (including regulators of carbohydrate utilization, fatty acid oxidation, and mitochondrial function) showed diurnal variation, with a general peak in the night. In contrast, pressure overload-induced cardiac hypertrophy completely abolished this diurnal variation of metabolic gene expression. Thus, over the course of the day, the normal heart anticipates, responds, and adapts to physiological alterations within its environment, a trait that is lost by the hypertrophied heart. We speculate that loss of plasticity of the hypertrophied heart may play a role in the subsequent development of contractile dysfunction.
Young
M E
ME
Department of Internal Medicine, Division of Cardiology, University of Texas-Houston Medical School, Houston, Texas, USA.
Razeghi
P
P
Cedars
A M
AM
Guthrie
P H
PH
Taegtmeyer
H
H
D000818:Animals; D001011:Aorta / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D050260:Carbohydrate Metabolism; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D051275:Glucose Transporter Type 4; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000235:genetics / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D017440:Photoperiod; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis
D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C495694:Slc2a4 protein, rat; D014157:Transcription Factors