Department of Physiology, University of Toronto, Medical Sciences Building 3247A, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada.
Pharmacol Rep. 2022 Oct;74(5):774-789. doi: 10.1007/s43440-022-00409-5. Epub 2022 Sep 9.
The brain orchestrates whole-body metabolism through an intricate system involving interneuronal crosstalk and communication. Specifically, a key player in this complex circuitry is the hypothalamus that controls feeding behaviour, energy expenditure, body weight and metabolism, whereby hypothalamic neurons sense and respond to circulating hormones, nutrients, and chemicals. Dysregulation of these neurons contributes to the development of metabolic disorders, such as obesity and type 2 diabetes. The involvement of hypothalamic microRNAs, post-transcriptional regulators of gene expression, in the central regulation of energy homeostasis has become increasingly apparent, although not completely delineated. This review summarizes current evidence demonstrating the regulation of feeding-related neuropeptides by brain-derived microRNAs as well as the regulation of specific miRNAs by nutrients and other peripheral signals. Moreover, the involvement of microRNAs in the central nervous system control of insulin, leptin, and estrogen signal transduction is examined. Finally, the therapeutic and diagnostic potential of microRNAs for metabolic disorders will be discussed and the regulation of brain-derived microRNAs by nutrients and other peripheral signals is considered. Demonstrating a critical role of microRNAs in hypothalamic regulation of energy homeostasis is an innovative route to uncover novel biomarkers and therapeutic candidates for metabolic disorders.
大脑通过涉及神经元相互交流和通讯的复杂系统来协调全身代谢。具体来说，这个复杂电路中的一个关键参与者是下丘脑，它控制着进食行为、能量消耗、体重和新陈代谢，下丘脑神经元感知和响应循环中的激素、营养物质和化学物质。这些神经元的失调导致代谢紊乱的发展，如肥胖和 2 型糖尿病。下丘脑 microRNAs 作为基因表达的转录后调节剂，在能量稳态的中枢调节中的作用越来越明显，尽管尚未完全阐明。这篇综述总结了目前的证据，证明了脑源性 microRNAs 对与进食相关的神经肽的调节，以及营养物质和其他外周信号对特定 microRNAs 的调节。此外，还研究了 microRNAs 参与胰岛素、瘦素和雌激素信号转导的中枢神经系统控制。最后，将讨论 microRNAs 在代谢紊乱中的治疗和诊断潜力，并考虑营养物质和其他外周信号对脑源性 microRNAs 的调节。证明 microRNAs 在下丘脑对能量稳态的调节中起着关键作用，这是揭示代谢紊乱新的生物标志物和治疗候选物的创新途径。
