The endocannabinoid system in the adipose organ.
The endocannabinoid system in the adipose organ.
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DOI：
10.1007/s11154-020-09623-z
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发表时间：
2022-03
影响因子：
8.2
通讯作者：
Piomelli D
中科院分区：
文献类型：
--
作者：
Jung KM;Lin L;Piomelli D
内源性大麻素系统存在于大多数（如果不是全部的话）哺乳动物器官中，并参与多种生理功能，从控制大脑突触可塑性到调节胃肠道平滑肌运动。这种信号复合物由G蛋白偶联的大麻素受体、这些受体的内源性配体（内源性大麻素）和负责这些配体形成和失活的酶/转运体组成。大麻素受体有两种亚型，CB1和CB2，以及两种主要的内源性大麻素，花生四烯酰基乙醇酰胺（anandamide）和2-花生四烯酰基sn-甘油（2-AG），它们通过不同磷脂前体的裂解根据需要产生。内源性大麻素系统的所有分子成分都存在于脂肪器官中，内源性大麻素信号被认为调节关键的稳态过程，包括脂肪生成、脂肪生成和热生成。重要的是，肥胖被发现与内脏脂肪库中过量的内源性大麻素活性有关，通过阻断CB1受体使这种活性正常化的治疗潜力已成为大量临床前和临床研究的重点。到目前为止，结果好坏参半，主要是由于大脑内源性大麻素在情绪和情绪调节方面的保护功能所产生的精神副作用的出现。对内源性大麻素系统在脂肪器官中所起作用的进一步研究将为肥胖的发病机制提供新的见解，并可能有助于找到利用这种信号复合物获得治疗益处的新方法。
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, CB1 and CB2, 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 CB1 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.
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