DataSheet1_Xiasangju alleviate metabolic syndrome by enhancing noradrenaline biosynthesis and activating brown adipose tissue.pdf

Metabolic syndrome (MetS) is a clinical condition associated with multiple metabolic risk factors leading to type 2 diabetes mellitus and other metabolic diseases. Recent evidence suggests that modulating adipose tissue to adaptive thermogenesis may offer therapeutic potential for MetS. Xiasangju (XSJ) is a marketed drug and dietary supplement used for the treatment of metabolic disease with anti-inflammatory activity. This study investigated the therapeutic effects of XSJ and the underlying mechanisms affecting the activation of brown adipose tissue (BAT) in MetS. The results revealed that XSJ ameliorated MetS by enhancing glucose and lipid metabolism, leading to reduced body weight and abdominal circumference, decreased adipose tissue and liver index, and improved blood glucose tolerance. XSJ administration stimulated catecholamine biosynthesis, increasing noradrenaline (NA) levels and activating NA-mediated proteins in BAT. Thus, BAT enhanced thermogenesis and oxidative phosphorylation (OXPHOS). Moreover, XSJ induced changes in gut microbiota composition, with an increase in Oscillibacter abundance and a decrease in Bilophila, Candidatus Stoquefichus, Holdemania, Parasutterella and Rothia. XSJ upregulated the proteins associated with intestinal tight junctions corresponding with lower serum lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α) monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) levels to maintain NA signaling transport. In summary, XSJ may alleviate MetS by promoting thermogenesis in BAT to ultimately boost energy metabolism through increasing NA biosynthesis, strengthening intestinal barrier integrity and reducing low-grade inflammation. These findings suggest XSJ has potential as a natural therapeutic agent for the treatment of MetS.

代谢综合征（MetS）是一类与多重代谢危险因素相关的临床病症，可诱发2型糖尿病及其他代谢性疾病。近期研究证据显示，调控脂肪组织以实现适应性产热，或可为代谢综合征带来治疗潜力。夏桑菊（XSJ）是一款已上市的药物及膳食补充剂，兼具抗炎活性，可用于代谢性疾病的治疗。本研究探究了夏桑菊（XSJ）对代谢综合征的治疗效果，及其调控棕色脂肪组织（BAT）激活的潜在分子机制。结果显示，夏桑菊可通过增强糖脂代谢改善代谢综合征，具体表现为体重与腹围降低、脂肪组织及肝脏指数下降，同时糖耐量得到改善。给予夏桑菊可刺激儿茶酚胺生物合成，提升去甲肾上腺素（NA）水平，并激活棕色脂肪组织中去甲肾上腺素介导的蛋白通路，由此增强棕色脂肪组织的产热与氧化磷酸化（OXPHOS）过程。此外，夏桑菊可改变肠道菌群组成：Oscillibacter的丰度显著升高，而Bilophila、Candidatus Stoquefichus、Holdemania、Parasutterella及Rothia的丰度则有所降低。夏桑菊还可上调肠道紧密连接相关蛋白的表达，同时降低血清脂多糖（LPS）、肿瘤坏死因子α（TNF-α）、单核细胞趋化蛋白-1（MCP-1）及白细胞介素-6（IL-6）水平，以维持去甲肾上腺素信号的正常转导。综上，夏桑菊或可通过以下途径缓解代谢综合征：提升去甲肾上腺素生物合成以促进棕色脂肪组织产热，最终增强能量代谢；同时强化肠道屏障完整性并减轻低度炎症反应。本研究结果表明，夏桑菊有望成为治疗代谢综合征的天然治疗药物。