Sousa Diana, Lopes Eduardo, Rosendo-Silva Daniela, Matafome Paulo
Coimbra Institute for Clinical and Biomedical Research (iCBR) and Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal.
Biomedicines. 2023 Feb 3;11(2):446. doi: 10.3390/biomedicines11020446.
Energy balance is regulated by several hormones and peptides, and neuropeptide Y is one of the most crucial in feeding and energy expenditure control. NPY is regulated by a series of peripheral nervous and humoral signals that are responsive to nutrient sensing, but its role in the energy balance is also intricately related to the energetic status, namely mitochondrial function. During fasting, mitochondrial dynamics and activity are activated in orexigenic neurons, increasing the levels of neuropeptide Y. By acting on the sympathetic nervous system, neuropeptide Y modulates thermogenesis and lipolysis, while in the peripheral sites, it triggers adipogenesis and lipogenesis instead. Moreover, both central and peripheral neuropeptide Y reduces mitochondrial activity by decreasing oxidative phosphorylation proteins and other mediators important to the uptake of fatty acids into the mitochondrial matrix, inhibiting lipid oxidation and energy expenditure. Dysregulation of the neuropeptide Y system, as occurs in metabolic diseases like obesity, may lead to mitochondrial dysfunction and, consequently, to oxidative stress and to the white adipose tissue inflammatory environment, contributing to the development of a metabolically unhealthy profile. This review focuses on the interconnection between mitochondrial function and dynamics with central and peripheral neuropeptide Y actions and discusses possible therapeutical modulations of the neuropeptide Y system as an anti-obesity tool.
能量平衡由多种激素和肽类调节，而神经肽Y是进食和能量消耗控制中最关键的一种。神经肽Y受一系列对营养感知有反应的外周神经和体液信号调节，但其在能量平衡中的作用也与能量状态密切相关，即线粒体功能。禁食期间，产热神经元中的线粒体动力学和活性被激活，神经肽Y水平升高。通过作用于交感神经系统，神经肽Y调节产热和脂肪分解，而在周围组织中，它反而会引发脂肪生成和脂质生成。此外，中枢和外周的神经肽Y都会通过降低氧化磷酸化蛋白和其他对脂肪酸进入线粒体基质摄取重要的介质来降低线粒体活性，抑制脂质氧化和能量消耗。神经肽Y系统失调，如在肥胖等代谢性疾病中发生的情况，可能导致线粒体功能障碍，进而导致氧化应激和白色脂肪组织炎症环境，促成代谢不健康状态的发展。本综述重点关注线粒体功能和动力学与中枢和外周神经肽Y作用之间的相互联系，并讨论将神经肽Y系统作为抗肥胖工具进行可能的治疗调节。
