Mattelaer Nele, Van der Schueren Bart, Van Oudenhove Lukas, Weltens Nathalie, Vangoitsenhoven Roman
Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
Laboratory for Brain-Gut Axis Studies, Translational Research in Gastrointestinal Disorders, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
Int J Obes (Lond). 2024 Oct;48(10):1363-1382. doi: 10.1038/s41366-024-01553-z. Epub 2024 Jun 4.
Major advances have been made in obesity treatment, focusing on restoring disturbances along the gut-brain axis. The endocannabinoid system (ECS) is a neuromodulatory signaling system, present along the entire gut-brain axis, that plays a critical role in central and peripheral regulation of food intake and body weight. Evidence on the impact of weight loss on the ECS is, however, more limited. Therefore, we set out to review the existing literature for changes in central and circulating endocannabinoid levels after bariatric surgery and other weight loss strategies in humans. The PubMed, Embase and Web of Science databases were searched for relevant articles. Fifty-six human studies were identified. Most studies measuring circulating 2-arachidonoylglycerol (2-AG) found no difference between normal weight and obesity, or no correlation with BMI. In contrast, studies measuring circulating arachidonoylethanolamine (AEA) found an increase or positive correlation with BMI. Two studies found a negative correlation between BMI and cannabinoid receptor type 1 (CB1) receptor availability in the brain. Only one study investigated the effect of pharmacological weight management on circulating endocannabinoid concentrations and found no effect on AEA concentrations. So far, six studies investigated potential changes in circulating endocannabinoids after bariatric surgery and reported conflicting results. Available evidence does not univocally support that circulating endocannabinoids are upregulated in individuals with obesity, which may be explained by variability across studies in several potential confounding factors (e.g. age and sex) as well as heterogeneity within the obesity population (e.g. BMI only vs. intra-abdominal adiposity). While several studies investigated the effect of lifestyle interventions on the circulating ECS, more studies are warranted that focus on pharmacologically and surgically induced weight loss. In addition, we identified several research needs which should be fulfilled to better understand the role of the ECS in obesity and its treatments.
肥胖治疗已取得重大进展，重点是恢复肠道-大脑轴的紊乱。内源性大麻素系统（ECS）是一种神经调节信号系统，存在于整个肠道-大脑轴中，在食物摄入和体重的中枢及外周调节中起关键作用。然而，关于体重减轻对ECS影响的证据更为有限。因此，我们着手回顾现有文献，以了解减肥手术和其他减肥策略对人体中枢和循环内源性大麻素水平的影响。在PubMed、Embase和科学网数据库中搜索相关文章。共识别出56项人体研究。大多数测量循环2-花生四烯酸甘油酯（2-AG）的研究发现，正常体重和肥胖之间没有差异，或者与BMI没有相关性。相比之下，测量循环花生四烯酸乙醇胺（AEA）的研究发现其增加或与BMI呈正相关。两项研究发现BMI与大脑中1型大麻素受体（CB1）的可用性呈负相关。只有一项研究调查了药物体重管理对循环内源性大麻素浓度的影响，发现对AEA浓度没有影响。到目前为止，六项研究调查了减肥手术后循环内源性大麻素的潜在变化，并报告了相互矛盾的结果。现有证据并不能明确支持肥胖个体的循环内源性大麻素上调，这可能是由于多项潜在混杂因素（如年龄和性别）在不同研究中的变异性以及肥胖人群内部的异质性（如仅BMI与腹内脂肪）所致。虽然有几项研究调查了生活方式干预对循环ECS的影响，但仍需要更多关注药物和手术诱导减肥的研究。此外，我们确定了几个研究需求，以更好地了解ECS在肥胖及其治疗中的作用。
