Insulin resistance and the sympathetic nervous system.
The obesity epidemic is driving metabolic (insulin resistance) syndrome-related health problems including an approximately threefold increased coronary heart disease risk. Sympathetic hyperfunction may participate in the pathogenesis and complications of the metabolic syndrome including higher blood pressure, a more active renin-angiotensin system, insulin resistance, faster heart rates, and excess cardiovascular disease including sudden death. Possible factors augmenting sympathetic activation in the metabolic syndrome include alterations of insulin, leptin, nonesterified fatty acids (NEFAs), cytokines, tri-iodothyronine, eicosanoids, sleep apnea, nitric oxide, endorphins, and neuropeptide Y. Of note, high plasma NEFAs are a risk factor for hypertension and sudden death. In short-term human studies, NEFAs can raise blood pressure, heart rate, and a(1)-adrenoceptor vasoreactivity, while reducing baroreflex sensitivity, endothelium-dependent vasodilatation, and vascular compliance. Efforts to further identify the mechanisms and consequences of sympathetic dysfunction in the metabolic syndrome may provide insights for therapeutic advances to ameliorate the excess cardiovascular risk and adverse outcomes.
Division of General Internal Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, CSB 826H, Charleston, SC 29425, USA. eganbm@musc.edu
Brent M
BM
Egan
D002318:Cardiovascular Diseases / Q000503:physiopathology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000502:physiology; D024821:Metabolic Syndrome / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology; D009765:Obesity / Q000503:physiopathology; D012307:Risk Factors; D012891:Sleep Apnea Syndromes / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000502:physiology* / Q000503:physiopathology
D005230:Fatty Acids, Nonesterified; D020738:Leptin