Myricetin-induced brown adipose tissue activation prevents obesity and insulin resistance in db/db mice
Myricetin-induced brown adipose tissue activation prevents obesity and insulin resistance in db/db mice
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杨梅素诱导的棕色脂肪组织活化可预防 db/db 小鼠的肥胖和胰岛素抵抗
DOI：
10.1007/s00394-017-1433-z
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发表时间：
2018-02-01
影响因子：
5
通讯作者：
Jin, Wanzhu
中科院分区：
文献类型：
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作者：
Hu, Tao;Yuan, Xiaoxue;Jin, Wanzhu
目的 杨梅素是一种膳食类黄酮，通过增加脂肪细胞中的葡萄糖转运和脂肪生成以及减轻肥胖中的全身炎症，在治疗肥胖和胰岛素抵抗方面是有效的。然而，杨梅素是否与紧密介导全身能量代谢的棕色脂肪组织（BAT）激活有关尚未揭示。因此，本研究评估了杨梅素是否能激活db/db小鼠的棕色脂肪组织。
方法 将溶解在蒸馏水中的杨梅素（400mg/kg）通过口服灌胃的方式，每日给予4周龄的瘦素受体缺陷型db/db雄性小鼠，持续14周。评估体重变化、葡萄糖耐量试验、血脂谱以及使用正电子发射断层扫描 - 计算机断层扫描（PET - CT）评估棕色脂肪组织的激活情况。
结果 经过14周的杨梅素治疗，db/db小鼠的全身胰岛素抵抗和肝脏脂肪变性显著改善，体重减轻，杨梅素导致肥胖程度降低，血浆脂质谱改善以及能量消耗增加。杨梅素通过上调产热蛋白表达和激活线粒体生物发生来激活棕色脂肪组织，最终在寒冷暴露后增加皮肤的散热。在皮下白色脂肪组织（iWAT）中，杨梅素诱导米色脂肪形成，增加产热蛋白表达并激活线粒体生物发生。一致地，在棕色脂肪细胞分化过程中将杨梅素引入C3H10T1/2细胞时，产热基因表达上调。此外，经过杨梅素治疗后，C3H10T1/2细胞、脂肪组织和血浆中脂联素的表达水平显著增加。
结论 这些结果强调杨梅素通过激活棕色脂肪组织以及增加棕色脂肪组织中脂联素的表达来预防肥胖和全身胰岛素抵抗。
Purpose Myricetin, a dietary flavonoid, is effective in the treatment of obesity and insulin resistance by increasing glucose transport and lipogenesis in adipocyte and diminishing systemic inflammation in obesity. However, it has not been revealed yet whether myricetin is associated with brown adipose tissue (BAT) activation that tightly mediates systemic energy metabolism. Therefore, this study assessed whether myricetin activated brown adipose tissue in db/db mouse.Methods Myricetin (400 mg/kg) in distilled water was fed daily by oral gavage to leptin receptor-deficient db/db male mice at 4 weeks of age for 14 weeks. Body weight change, glucose intolerance test, blood lipid profile and BAT activation using PET-CT were assessed.Results After myricetin treatment for 14 weeks, systemic insulin resistance and hepatic steatosis were significantly improved in db/db mice with body weight reduction and myricetin led to decreased adipocity, improved plasma lipid profiles and increased energy expenditure. Myricetin activated BAT by upregulating thermogenic protein expression and activating mitochondrial biogenesis, eventually increasing heat dissipation in skin after cold exposure. In iWAT, myricetin induced beige formation, increased thermogenic protein expression and activated mitochondrial biogenesis. Consistently, thermogenic gene expression was upregulated when myricetin was introduced in C3H10T1/2 cells during brown adipocytes differentiation. Moreover, the expression level of adiponectin was significantly increased in C3H10T1/2 cells, adipose tissues and plasma after myricetin treatment.Conclusions These results highlight that myricetin prevents obesity and systemic insulin resistance by activating BAT and increasing adiponectin expression in BAT.