Department of Physiology and Biophysics, Cardiorenal and Metabolic Diseases Research Center, Mississippi Center for Obesity Research, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, USA.
Curr Hypertens Rep. 2024 Nov 29;27(1):2. doi: 10.1007/s11906-024-01318-z.
The role of leptin in regulating cardiac function is still controversial with conflicting results in clinical and preclinical studies. However, most previous studies have not considered leptin's powerful cardiac effects that are mediated via activation of central nervous system (CNS) leptin receptors (LepRs) which, in turn, elicit major improvements in cardiac metabolism. In this review, we focus mainly on the role of leptin in regulating cardiac function via its CNS LepRs and downstream signaling pathways, such as the brain melanocortin system.
Studies from our laboratory showed that CNS LepR activation, without raising plasma leptin levels, has remarkable beneficial effects on cardiac metabolism and function that protect the heart during pathological conditions, including heart failure (HF) induced by myocardial infarction (MI). These cardioprotective effects of leptin appear to be mediated by stimulation of CNS proopiomelanocortin neurons and subsequent activation of melanocortin 4 receptors (MC4R) in the brain. Chronic activation of the brain leptin-melanocortin pathway improves cardiac function and metabolism following myocardial infarction. However, the mechanism underlying this brain-heart crosstalk remains unclear and may have important implications for the development of new therapies for MI and HF.
瘦素在调节心脏功能中的作用仍存在争议，临床和临床前研究的结果相互矛盾。然而，大多数先前的研究都没有考虑到瘦素通过中枢神经系统（CNS）瘦素受体（LepR）发挥的强大的心脏效应，反过来，这会引发心脏代谢的重大改善。在这篇综述中，我们主要关注瘦素通过其 CNS LepR 及其下游信号通路（如脑黑皮质素系统）调节心脏功能的作用。
我们实验室的研究表明，CNS LepR 的激活，在不提高血浆瘦素水平的情况下，对心脏代谢和功能有显著的有益影响，可以在病理条件下保护心脏，包括心肌梗死（MI）引起的心力衰竭（HF）。瘦素的这些心脏保护作用似乎是通过刺激中枢前阿黑皮素原神经元和随后在大脑中激活黑皮质素 4 受体（MC4R）来介导的。慢性激活大脑瘦素-黑皮质素通路可改善心肌梗死后的心脏功能和代谢。然而，这种大脑-心脏相互作用的机制尚不清楚，这可能对 MI 和 HF 的新疗法的发展具有重要意义。
