BACKGROUND & AIMS:
:Nowadays, obesity and its associated metabolic disorders, including diabetes, metabolic syndrome, cardiovascular disease, or cancer, continue to be a health epidemic in westernized societies, and there is an increased necessity to explore anti-obesity therapies including pharmaceutical and nutraceutical compounds. Considerable attention has been placed on the identification of bioactive compounds from natural sources to manage the metabolic stress associated with obesity. In a previous work, we have demonstrated that a CO2 supercritical fluid extract from yarrow (Yarrow SFE), downregulates the expression of the lipogenic master regulator SREBF1 and its downstream molecular targets FASN and SCD in a tumoral context. Since obesity and diabetes are strongly considered high-risk factors for cancer development, herein, we aimed to investigate the potential therapeutic role of Yarrow SFE in the metabolic stress induced after a high-fat diet in mice. For this purpose, 32 C57BL/6 mice were distributed in four groups according to their diets: standard diet (SD); SD supplemented with Yarrow SFE (SD + Yarrow); high-fat diet (HFD); and HFD supplemented with Yarrow SFE (HFD + Yarrow). Fasting glycemia, insulin levels, homeostasis model assessment for insulin resistance (HOMA-IR), lipid profile, gene expression, and lipid content of liver and adipose tissues were analyzed after three months of treatment. Results indicate improved fasting glucose levels in plasma, enhanced insulin sensitivity, and diminished hypercholesterolemia in the HFD + Yarrow group compared to the HFD group. Mechanistically, Yarrow SFE protects liver from steatosis after the HFD challenge by augmenting the adipose tissue buffering capacity of the circulating plasma glucose.
背景与目标:
: 如今,肥胖及其相关的代谢性疾病,包括糖尿病,代谢综合征,心血管疾病或癌症,在西方社会中继续成为健康流行病,并且越来越有必要探索包括药物和营养药物在内的抗肥胖疗法化合物。已经非常重视从天然来源鉴定生物活性化合物,以管理与肥胖相关的代谢应激。在先前的工作中,我们已经证明了来自yarrow (Yarrow SFE) 的CO2超临界流体提取物在肿瘤环境中下调了脂肪生成主调节剂SREBF1及其下游分子靶标FASN和SCD的表达。由于肥胖和糖尿病被强烈认为是癌症发展的高危因素,因此,我们旨在研究Yarrow SFE在小鼠高脂饮食后诱导的代谢应激中的潜在治疗作用。为此,根据其饮食将32只C57BL/6小鼠分为四组: 标准饮食 (SD); SD补充了Yarrow SFE (SD Yarrow); 高脂饮食 (HFD); 和HFD补充了Yarrow SFE (HFD Yarrow)。治疗三个月后,分析空腹血糖,胰岛素水平,稳态模型评估胰岛素抵抗 (homa-ir),脂质分布,基因表达以及肝脏和脂肪组织的脂质含量。结果表明,与HFD组相比,HFD Yarrow组的血浆空腹血糖水平提高,胰岛素敏感性增强,高胆固醇血症减少。从机制上讲,Yarrow SFE通过增强循环血浆葡萄糖的脂肪组织缓冲能力来保护肝脏免受HFD攻击后的脂肪变性。