慢性低度炎症(CLGI)与肥胖有关,是其发病机制之一。脂多糖(LPS),革兰氏阴性细菌细胞壁的组成部分,是CLGI的主要原因。研究发现辣椒素显著降低了产生LPS的细菌的相对丰度。在本研究中,以TRPV1敲除(TRPV1-/-)C57BL/6J小鼠和肠上皮细胞系Caco-2(TRPV1-/-)为模型,确定辣椒素对CLGI的影响,并阐明其在体内和体外介导体重减轻的机制。我们发现辣椒素的胃内给药显著减弱了体重的增加,食物摄入量,血脂,高脂饮食的TRPV1-/-小鼠的血糖,提示辣椒素的抗肥胖作用。辣椒素通过降低幽门螺杆菌等变形杆菌的相对丰度来降低肠道中的LPS水平,Desulfovibrio,还有Sutterilla.Toll样受体4(TLR4)水平随着LPS水平的降低而降低。然后,通过减少TLR4介导的肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6的表达,可以减少肠道局部炎症。减轻局部肠道炎症导致紧密连接蛋白闭塞带1(ZO-1)和闭塞蛋白的表达增加,并恢复肠屏障功能。辣椒素在转录和翻译水平上增加了ZO-1和occludin的表达,从而增加跨内皮电阻并恢复肠屏障功能。肠屏障功能的恢复降低肠通透性,这降低了进入循环的LPS的浓度,和减少的内毒素血症导致炎性细胞因子如TNF-α和IL-6的血清浓度降低,从而减弱CLGI。本研究揭示了辣椒素通过降低CLGI的抗肥胖作用及其机制。增加我们对辣椒素抗肥胖作用的了解。已经证实辣椒素可以刺激肠道跨膜蛋白ZO-1和胞质蛋白occludin的表达,增加跨上皮电电阻值,修复肠屏障功能。
Chronic low-grade inflammation (CLGI) is associated with obesity and is one of its pathogenetic mechanisms. Lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls, is the principal cause of CLGI. Studies have found that
capsaicin significantly reduces the relative abundance of LPS-producing bacteria. In the present study, TRPV1-knockout (TRPV1-/-) C57BL/6J mice and the intestinal epithelial cell line Caco-2 (TRPV1-/-) were used as models to determine the effect of capsaicin on CLGI and elucidate the mechanism by which it mediates weight loss in vivo and in vitro. We found that the intragastric administration of
capsaicin significantly blunted increases in body weight, food intake, blood lipid, and blood glucose in TRPV1-/- mice fed a high-fat diet, suggesting an anti-obesity effect of capsaicin.
Capsaicin reduced LPS levels in the intestine by reducing the relative abundance of Proteobacteria such as Helicobacter, Desulfovibrio, and Sutterella. Toll-like receptor 4 (TLR4) levels decreased following decreases in LPS levels. Then, the local inflammation of the intestine was reduced by reducing the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mediated by TLR4. Attenuating local intestinal inflammation led to the increased expression of tight junction proteins zonula occludens 1 (ZO-1) and occludin and the restoration of the intestinal barrier function. Capsaicin increased the expression of ZO-1 and occludin at the transcriptional and translational levels, thereby increasing trans-endothelial electrical resistance and restoring intestinal barrier function. The restoration of intestinal barrier function decreases intestinal permeability, which reduces the concentration of LPS entering the circulation, and reduced endotoxemia leads to decreased serum concentrations of inflammatory cytokines such as TNF-α and IL-6, thereby attenuating CLGI. This study sheds light on the anti-obesity effect of capsaicin and its mechanism by reducing CLGI, increasing our understanding of the anti-obesity effects of
capsaicin. It has been confirmed that
capsaicin can stimulate the expression of intestinal transmembrane protein ZO-1 and cytoplasmic protein occludin, increase the trans-epithelial electrical resistance value, and repair intestinal barrier function.