Department of Anatomy and Neurobiology, University of California, Irvine, 3101 Gillespie NRF, Irvine, CA, 92697-1275, USA.
Department of Pharmacology, University of California, Irvine, Irvine, CA, 92697, USA.
Rev Endocr Metab Disord. 2022 Feb;23(1):51-60. doi: 10.1007/s11154-020-09623-z. Epub 2021 Jan 2.
The endocannabinoid system is found in most, if not all, mammalian organs and is involved in a variety of physiological functions, ranging from the control of synaptic plasticity in the brain to the modulation of smooth muscle motility in the gastrointestinal tract. This signaling complex consists of G protein-coupled cannabinoid receptors, endogenous ligands for those receptors (endocannabinoids) and enzymes/transporters responsible for the formation and deactivation of these ligands. There are two subtypes of cannabinoid receptors, CB and CB, and two major endocannabinoids, arachidonoylethanolamide (anandamide) and 2-arachidonoyl-sn-glycerol (2-AG), which are produced upon demand through cleavage of distinct phospholipid precursors. All molecular components of the endocannabinoid system are represented in the adipose organ, where endocannabinoid signals are thought to regulate critical homeostatic processes, including adipogenesis, lipogenesis and thermogenesis. Importantly, obesity was found to be associated with excess endocannabinoid activity in visceral fat depots, and the therapeutic potential of normalizing such activity by blocking CB receptors has been the focus of substantial preclinical and clinical research. Results have been mixed thus far, mostly owing to the emergence of psychiatric side effects rooted in the protective functions served by brain endocannabinoids in mood and affect regulation. Further studies about the roles played by the endocannabinoid system in the adipose organ will offer new insights into the pathogenesis of obesity and might help identify new ways to leverage this signaling complex for therapeutic benefit.
内源性大麻素系统存在于大多数哺乳动物器官中，如果不是全部的话，它参与了多种生理功能，从大脑中突触可塑性的控制到胃肠道平滑肌运动的调节。这个信号复合物由 G 蛋白偶联大麻素受体、这些受体的内源性配体（内源性大麻素）以及负责这些配体形成和失活的酶/转运体组成。有两种亚型的大麻素受体，CB 和 CB，两种主要的内源性大麻素，花生四烯酰乙醇胺（花生四烯酸）和 2-花生四烯酰-sn-甘油（2-AG），它们是通过切割不同的磷脂前体按需产生的。内源性大麻素系统的所有分子成分都存在于脂肪组织中，内源性大麻素信号被认为调节关键的体内平衡过程，包括脂肪生成、脂肪生成和生热作用。重要的是，肥胖与内脏脂肪储存中内源性大麻素活性过剩有关，通过阻断 CB 受体使这种活性正常化的治疗潜力一直是大量临床前和临床研究的焦点。到目前为止，结果喜忧参半，主要是由于大脑内源性大麻素在情绪和情感调节中的保护作用所产生的精神副作用。进一步研究内源性大麻素系统在脂肪组织中的作用将为肥胖的发病机制提供新的见解，并可能有助于确定利用这种信号复合物获得治疗益处的新方法。
