Izzi-Engbeaya Chioma, Dhillo Waljit S
Section of Endocrinology & Investigative Medicine, Imperial College London, London, UK.
Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust, London, UK.
J Physiol. 2022 Mar;600(5):1079-1088. doi: 10.1113/JP281712. Epub 2021 May 29.
Kisspeptin, a neuropeptide hormone, has been firmly established as a key regulator of the hypothalamic-pituitary-gonadal axis and mammalian reproductive behaviour. In recent years, a growing body of evidence has emerged suggesting a role for kisspeptin in regulating metabolic processes. This data suggest that kisspeptin exerts its metabolic effects indirectly via gonadal hormones and/or directly via the kisspeptin receptor in the brain, pancreas and brown adipose tissue. Kisspeptin receptor knockout studies indicate that kisspeptin may play sexually dimorphic roles in the physiological regulation of energy expenditure, food intake and body weight. Some, but not all, in vitro work demonstrates positive effects on glucose-stimulated insulin secretion, which is more marked at higher kisspeptin concentrations. Acute and chronic in vivo rodent, non-human primate and human studies reveal enhancement of glucose-stimulated insulin secretion in response to pharmacological doses of kisspeptin. Although significant progress has been made in elucidating the metabolic effects of kisspeptin, further mechanistic work and translational studies are required to address unanswered questions and establish the metabolic effects of kisspeptin in diverse human populations (including women, people with obesity and people with diabetes).
kisspeptin是一种神经肽激素,已被确认为下丘脑-垂体-性腺轴及哺乳动物生殖行为的关键调节因子。近年来,越来越多的证据表明kisspeptin在调节代谢过程中发挥作用。这些数据表明,kisspeptin通过性腺激素间接发挥其代谢作用,和/或通过大脑、胰腺及棕色脂肪组织中的kisspeptin受体直接发挥作用。kisspeptin受体基因敲除研究表明,kisspeptin在能量消耗、食物摄入及体重的生理调节中可能发挥性别差异作用。部分(而非全部)体外研究显示,kisspeptin对葡萄糖刺激的胰岛素分泌有积极作用,且在较高浓度的kisspeptin作用下更为显著。啮齿动物、非人灵长类动物及人类的急性和慢性体内研究表明,药理剂量的kisspeptin可增强葡萄糖刺激的胰岛素分泌。尽管在阐明kisspeptin的代谢作用方面已取得显著进展,但仍需进一步开展机制研究和转化研究,以解决未解答的问题,并确定kisspeptin在不同人群(包括女性、肥胖者及糖尿病患者)中的代谢作用。