Obesity: sex and sympathetics

Abstract

Obesity increases sympathetic nerve activity (SNA) in men, but not women. Here, we review current evidence suggesting that sexually dimorphic sympathoexcitatory responses to leptin and insulin may contribute. More specifically, while insulin increases SNA similarly in lean males and females, this response is markedly amplified in obese males, but is abolished in obese females. In lean female rats, leptin increases a subset of sympathetic nerves only during the high estrogen proestrus reproductive phase; thus, in obese females, because reproductive cycling can become impaired, the sporadic nature of leptin-induced sympathoexcitaton could minimize its action, despite elevated leptin levels. In contrast, in males, obesity preserves or enhances the central sympathoexcitatory response to leptin, and current evidence favors leptin's contribution to the well-established increases in SNA induced by obesity in men. Leptin and insulin increase SNA via receptor binding in the hypothalamic arcuate nucleus and a neuropathway that includes arcuate neuropeptide Y (NPY) and proopiomelanocortin (POMC) projections to the paraventricular nucleus. These metabolic hormones normally suppress sympathoinhibitory NPY neurons and activate sympathoexcitatory POMC neurons. However, obesity appears to alter the ongoing activity and responsiveness of arcuate NPY and POMC neurons in a sexually dimorphic way, such that SNA increases in males but not females. We propose hypotheses to explain these sex differences and suggest areas of future research.

Leptin and Obesity: Role and Clinical Implication

“…Furthermore, in contrast to insulin, which induces improvement in SNA by acting in ARC as the only specific site, leptin takes action in few hypothalamic sites, all of which seem to interact in PVN ( 128 ). The main effects of insulin and leptin in states of obesity include sexually dimorphic alterations.…”

“…The main effects of insulin and leptin in states of obesity include sexually dimorphic alterations. The latest observations regarding the link between sexual dimorphism and sympathetic in the obese human population reveal that several variations exist in lean females that restrict the effects of leptin and insulin to increase SNA and/or BP ( 128 ). The first is that only during proestrus leptin increases SNA by the synergistic effects of raised concentrations of estrogen.…”

Sympathetic activation: a potential link between comorbidities and COVID‐19

“…In obesity, diabetes, and metabolic syndrome, sympathetic overactivity has been ascribed to high levels of circulating insulin and leptin, which stimulate the sympathetic outflow both centrally and peripherally, and/or to chronic intermittent hypoxia due to obstructive sleep apnea [18,19]. Sympathetic overactivation in turn increases insulin resistance, maintaining a positive feedback loop [20].…”

Phloretin ameliorates hepatic steatosis through regulation of lipogenesis and Sirt1/AMPK signaling in obese mice

“…Refined foods and junk food increase the prevalence of obesity, which is a risk factor for chronic diseases, including cardiovascular disease, atherosclerosis, type 2 diabetes, and cancer [ 1 ]. Obesity not only increases the lipid accumulation of visceral fat tissue, but also induces excessive lipid accumulation in the liver and causes fatty liver disease [ 2 ].…”