Wei Qiong, Lee Jong Han, Wu Chia-Shan, Zang Qun S, Guo Shaodong, Lu Hui-Chen, Sun Yuxiang
Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China.
Department of Pediatrics, USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, United States.
World J Diabetes. 2021 Oct 15;12(10):1750-1764. doi: 10.4239/wjd.v12.i10.1750.
Antagonists of cannabinoid type 1 receptor () have been shown to promote body weight loss and improve insulin sensitivity. Cannabinoids decrease adiponectin, and blocker increase adiponectin. However, the mediators of actions are not well defined.
To investigate whether the beneficial effects of inhibition are, at least in part, mediated by adiponectin.
We compared metabolic and inflammatory phenotypes of wild-type (WT) mice, -null ( ) and /adiponectin double-knockout (DKO) mice. We assessed the insulin sensitivity using insulin tolerance test and glucose tolerance test, and inflammation using flow cytometry analysis of macrophages.
mice exhibited significantly reduced body weight and fat mass when compared to WT mice. While no significance was found in total daily food intake and locomotor activity, mice showed increased energy expenditure, enhanced thermogenesis in brown adipose tissue (BAT), and improved insulin sensitivity compared to WT mice. DKO showed no difference in body weight, adiposity, nor insulin sensitivity; only showed a modestly elevated thermogenesis in BAT compared to mice. The metabolic phenotype of DKO is largely similar to mice, suggesting that adiponectin is not a key mediator of the metabolic effects of . Interestingly, mice showed reduced pro-inflammatory macrophage polarization in both peritoneal macrophages and adipose tissue macrophages compared to WT mice; in contrast, DKO mice exhibited increased pro-inflammatory macrophage polarization in these macrophages compared to mice, suggesting that adiponectin is an important mediator of the inflammatory effect of .
Our findings reveal that functions through both adiponectin-dependent and adiponectin-independent mechanisms: regulates energy metabolism in an adiponectin-independent manner, and inflammation in an adiponectin-dependent manner. The differential effects of adiponectin on -mediated metabolic and inflammatory functions should be taken into consideration in antagonist utilization.
1型大麻素受体（）拮抗剂已被证明可促进体重减轻并改善胰岛素敏感性。大麻素会降低脂联素水平，而拮抗剂会增加脂联素水平。然而，作用的介导因子尚未明确。
研究抑制作用的有益效果是否至少部分由脂联素介导。
我们比较了野生型（WT）小鼠、基因敲除（）小鼠和/脂联素双敲除（DKO）小鼠的代谢和炎症表型。我们通过胰岛素耐量试验和葡萄糖耐量试验评估胰岛素敏感性，并通过巨噬细胞的流式细胞术分析评估炎症。
与WT小鼠相比，小鼠体重和脂肪量显著降低。虽然每日总食物摄入量和运动活动没有显著差异，但与WT小鼠相比，小鼠能量消耗增加，棕色脂肪组织（BAT）产热增强，胰岛素敏感性提高。DKO小鼠在体重、肥胖程度和胰岛素敏感性方面没有差异；与小鼠相比，仅BAT产热略有升高。DKO小鼠的代谢表型与小鼠基本相似，表明脂联素不是作用的代谢效应的关键介导因子。有趣的是，与WT小鼠相比，小鼠腹膜巨噬细胞和脂肪组织巨噬细胞中促炎巨噬细胞极化减少；相反，与小鼠相比，DKO小鼠在这些巨噬细胞中促炎巨噬细胞极化增加，表明脂联素是作用的炎症效应的重要介导因子。
我们的研究结果表明，通过脂联素依赖和脂联素非依赖机制发挥作用：以脂联素非依赖方式调节能量代谢，以脂联素依赖方式调节炎症。在使用拮抗剂时，应考虑脂联素对介导的代谢和炎症功能的不同影响。
