Department of Physiology and Pharmacology, L-334, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
Biol Sex Differ. 2020 Mar 11;11(1):10. doi: 10.1186/s13293-020-00286-8.
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.
肥胖会增加男性的交感神经活动（SNA），但不会增加女性的交感神经活动。在这里，我们回顾了目前的证据，表明瘦素和胰岛素的性别二态性交感兴奋反应可能与此有关。更具体地说，虽然胰岛素同样会增加瘦男性和女性的 SNA，但这种反应在肥胖男性中明显增强，而在肥胖女性中则被消除。在瘦雌性大鼠中，只有在高雌激素发情期生殖阶段，瘦素才会增加一部分交感神经；因此，在肥胖女性中，由于生殖周期可能受损，瘦素诱导的交感兴奋的偶发性可能会削弱其作用，尽管瘦素水平升高。相比之下，在男性中，肥胖会保留或增强对瘦素的中枢交感兴奋反应，目前的证据表明，瘦素对男性肥胖引起的 SNA 增加有贡献。瘦素和胰岛素通过在下丘脑弓状核中的受体结合以及包括弓状神经肽 Y（NPY）和促黑细胞皮质素原（POMC）投射到室旁核的神经通路来增加 SNA。这些代谢激素通常会抑制抑制交感神经的 NPY 神经元并激活兴奋交感神经的 POMC 神经元。然而，肥胖似乎以一种性别二态的方式改变了弓状 NPY 和 POMC 神经元的持续活动和反应性，使得 SNA 在男性中增加而在女性中不增加。我们提出了一些假设来解释这些性别差异，并提出了未来研究的领域。
