Insulin-mediated sympathetic stimulation: role in the pathogenesis of obesity-related hypertension (or, how insulin affects blood pressure, and why)

Abstract

Thus, the evidence summarized here supports an important role for insulin and the sympathetic nervous system in the pathogenesis of obesity-related hypertension. Is it possible that insulin-mediated sympathetic stimulation contributes a pro-hypertensive effect in non-obese as well? It seems possible in young borderline hypertensives where sympathetically mediated thermogenic mechanisms are potent enough to compensate for the increased caloric intake, thereby enabling these young hypertensives to avoid obesity. This is consistent with an observation made in the original Framingham cohort that not only did obesity predict the eventual development of hypertension, but hypertension, as well, predicted the eventual development of obesity. A reasonable interpretation of these data suggests that as subjects age and the effectiveness of thermogenic mechanisms wanes, obesity might develop as a consequence of increased caloric intake no longer effectively buffered by the increased SNS activity. It is important to note that the mechanisms described here exert a pro-hypertensive effect and cannot properly be considered to 'cause' hypertension. Hypertension is rarely the consequence of a single mechanism. It is also true, as pointed out convincingly by Julius and his colleagues, that enhanced sympathetic activity, as a primary factor, can be associated with both hypertension, insulin resistance and, possibly, obesity [39]. And, finally, it should be noted that the mechanism described here is not the only mechanism linking obesity and hypertension. A rapidly emerging body of evidence indicates that leptin, the polypeptide product of the ob/ob gene secreted from adipose tissue, exerts potent central neural effects on both appetite and sympathetic activity. Leptin levels, elevated in obese humans, have the potential to increase both sympathetic activity and blood pressure [40-43]. A more comprehensive summary of the relationships between hypertension and obesity may, therefore, involve insulin and leptin, as well as the SNS, as represented in the schema presented in Figure 7. Both leptin and insulin may, therefore, be considered as compensatory mechanisms recruited to restore energy balance, with the SNS as one of the effector arms. Viewed in this way, obesity-related hypertension is inextricably linked to the metabolic economy of the obese.

Visceral adiposity, not abdominal subcutaneous fat area, is associated with high blood pressure in Japanese men: the Ohtori study

“…This pathophysiological link may be partly mediated by insulin resistance. [34][35][36][37] In this study, as the association between visceral adiposity and hypertension was independent of insulin resistance, visceral adiposity may affect hypertension through mechanisms unrelated to fasting plasma insulin.…”

Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity

“…They have long been recognized to be diseases of civilization with a very gradual onset, the result of complex interplay between genetic susceptibility and environmental factors, and with insulin resistance often appearing as a relatively early development in all three entities. [1][2][3] What triggers the onset of insulin resistance (ie, the decreased ability of peripheral target tissues to respond properly to normal circulating concentrations of insulin) is not clear. However, since during insulin stimulation the skeletal muscle is the major site for glucose disposal, 4 defects in insulin-mediated glucose uptake and in its metabolic fate in this tissue are thought to be early events in the pathogenesis of insulin resistance.…”

Insulin resistance and the metabolic syndrome

“…Mammals may have developed the capacity for dietary thermogenesis as an evolutionary adaptation to dietary deficiencies, particularly diets low in protein. By overeating a low protein diet, an organism might be able to satisfy basic nitrogen requirements for growth and development, without the accompanying liability of excessive fat accumulation [14]. Whatever the evolutionary origins, it is clear that dietary thermogenesis can act as a buffer against the development of obesity.…”