Octacosanol and policosanol prevent high-fat diet-induced obesity and metabolic disorders by activating brown adipose tissue and improving liver metabolism
Octacosanol and policosanol prevent high-fat diet-induced obesity and metabolic disorders by activating brown adipose tissue and improving liver metabolism
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DOI：
10.1038/s41598-019-41631-1
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发表时间：
2019-03-26
影响因子：
4.6
通讯作者：
Shimano, Hitoshi
中科院分区：
文献类型：
--
作者：
Sharma, Rahul;Matsuzaka, Takashi;Shimano, Hitoshi
棕色脂肪组织（BAT）是治疗肥胖和代谢性疾病的一个有吸引力的治疗靶点。八烷醇是多酚醇的主要成分，多酚醇是一种从植物中提取的长链脂肪醇的混合物。本研究旨在探讨八烷糖醇和十烷糖醇对高脂肪饮食（HFD）引起的肥胖的影响。小鼠分别以鼠粮或HFD喂养，并分别给予或不给予八烷糖醇或多酚糖醇4周。饲料饲喂小鼠的体重和体脂明显高于饲料饲喂小鼠。然而，用八糖醇或三聚糖醇（HFDo/p）处理的HFD喂养的小鼠，体重增加、体脂增加、胰岛素抵抗和肝脏脂质含量均较低。八糖醇或胆糖醇治疗后的下体脂肪增加与BAT活性增加、参与脂肪生成和肝脏胆固醇摄取的基因表达减少以及白色脂肪组织（WAT）炎症改善有关。此外，八糖醇和多糖醇显著增加了编码多不饱和脂肪酸受体的基因Ffar4的表达，该基因可激活BAT产热。总之，这些结果表明八烷糖醇和多酚糖醇通过增加BAT活性和改善肝脏脂质代谢来改善饮食引起的肥胖和代谢紊乱。因此，这些脂质代表了预防和治疗肥胖和肥胖相关代谢紊乱的有希望的治疗靶点。
Brown adipose tissue (BAT) is an attractive therapeutic target for treating obesity and metabolic diseases. Octacosanol is the main component of policosanol, a mixture of very long chain aliphatic alcohols obtained from plants. The current study aimed to investigate the effect of octacosanol and policosanol on high-fat diet (HFD)-induced obesity. Mice were fed on chow, or HFD, with or without octacosanol or policosanol treatment for four weeks. HFD-fed mice showed significantly higher body weight and body fat compared with chow-fed mice. However, mice fed on HFD treated with octacosanol or policosanol (HFDo/p) showed lower body weight gain, body fat gain, insulin resistance and hepatic lipid content. Lower body fat gain after octacosanol or policosanol was associated with increased BAT activity, reduced expression of genes involved in lipogenesis and cholesterol uptake in the liver, and amelioration of white adipose tissue (WAT) inflammation. Moreover, octacosanol and policosanol significantly increased the expression of Ffar4, a gene encoding polyunsaturated fatty acid receptor, which activates BAT thermogenesis. Together, these results suggest that octacosanol and policosanol ameliorate diet-induced obesity and metabolic disorders by increasing BAT activity and improving hepatic lipid metabolism. Thus, these lipids represent promising therapeutic targets for the prevention and treatment of obesity and obesity-related metabolic disorders.