Does selective leptin resistance causeobesity-related hypertension?

Obesity is a major risk factor for hypertension, diabetes and cardiovascular disease. Leptin is a hormone producedby adipocytes, which has effects on the central nervous system. Leptinemia is increased in obesity and is associated with increased sympathetic nerve activity. Therefore, it is possible that obesity-related hypertension is caused in part by leptin-dependent sympathoactivation. However, obese subjects exhibit resistance to the anorexic and metabolic effects of leptin. One potential explanation forthis paradox is selective leptin resistance. Animal models of obesity demonstrate preserved sympathetic actions of leptin despite resistance to its anorexic and metabolic actions. Abnormalities of intracellular signaling at certain central neural pathways may provide the molecular and anatomical bases of selective leptin resistance. Characterization of these pathways could lead to new approaches to the management of obesity-related hypertension.

Mechanisms of obesity-related hypertension: from insulin to leptin

Hyperinsulinemia has been classically associated with obesity-related hypertension. However, this concept has been challenged given that acute hyperinsulinemia has repeatedly failed to increase arterial pressure in humans. Most recently, leptin-dependent mechanisms have raised great interest as potential explanations for obesity-related hypertension. Despite potential depressor effects of leptin, most reports have shown that leptin increases arterial pressure probably due to sympathetic activation. Human obesity hypertension is associated with increased sympathetic activity. Thus, it is possible that hyperleptinemia in human obesity could contribute to obesity-related sympathetic activation. However, human obesity is a partial leptin resistant condition. The novel concept of selective leptin resistance may help explain leptin-induced sympathoactivation in obese subjects resistant to the metabolic effects of leptin. In this review article, we revisit insulin-dependent mechanisms reportedly associated with obesity hypertension. We also discuss leptin actions on the cardiovascular system and show experimental results that support the concept of selective leptin resistance.