Insulin resistance, energy balance and sympathetic nervous system activity.
Insulin resistance and hyperinsulinemia are commonly associated with hypertension in the obese. The nature of this association is obscure. An hypothesis is developed that attributes obesity-related hypertension to sympathetic stimulation. The relationship between insulin and the sympathetic nervous system (SNS) has its origins in the mediation of dietary thermogenesis. Fasting suppresses while carbohydrate and fat feeding stimulate sympathetic activity. Insulin-mediated glucose metabolism within critical central neurons links dietary intake and central sympathetic outflow. The sympathetic nervous system, in turn, contributes to changes in metabolic rate that accompany alterations in dietary intake. It is hypothesized that insulin resistance is a mechanism recruited in the obese to limit further weight gain and stabilize body mass. Insulin-mediated sympathetic stimulation is one mechanism that may restore energy balance in the obese since the obese are not resistant to the stimulatory effect of insulin on the SNS. Sympathetically mediated stimulation of the heart, vasculature and kidney contributes, in genetically predisposed individuals, to the development of hypertension. Viewed in this light, obesity-related hypertension is the unfortunate by-product of an adaptive mechanism (insulin resistance) recruited to restore energy balance in the obese. Possible implications of this formulation are discussed.
Department of Medicine, Harvard Medical School, Boston, MA.
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Landsberg
D000273:Adipose Tissue / Q000473:pathology; D001794:Blood Pressure / Q000502:physiology; D004032:Diet; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications / Q000503:physiopathology; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology*; D008954:Models, Biological; D009765:Obesity / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000502:physiology*