Octacosanol and policosanol prevent high-fat diet-induced obesity and metabolic disorders by activating brown adipose tissue and improving liver metabolism

Rahul Kumar Sharma ,Mahesh K Kaushik,Yuka Okajima,Yang Ma,Takashi Matsuzaka,Yuhei Mizunoe,Kaori Motomura,Yunong Wang,Shigeru Yatoh,Takuya Shimura,Motohiro Sekiya,Hitoshi Iwasaki,Takafumi Miyamoto,Song‐Iee Han ,Yuichi Aita,Hiroaki Suzuki,Zahara M Saber,Yoshimi Nakagawa,Naoya Yahagi,Yoshinori Takeuchi,Takehito Sugasawa,Hiroshi Ohno,Hitoshi Shimano

doi:10.1038/s41598-019-41631-1

Abstract

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.

Highlights

Brown adipose tissue (BAT) is an attractive therapeutic target for treating obesity and metabolic diseases
The fat mass gain was significantly less in mice fed on HFD treated with octacosanol or policosanol (HFDo/p) compared with high-fat diet (HFD)-fed mice (Fig. 1c)
The weight of epididymal white adipose tissue (WAT) (Fig. 1f), inguinal WAT (iWAT) (Fig. 1g) and brown adipose tissue (BAT) (Fig. 1h) was significantly reduced in HFD-fed mice supplemented with octacosanol and policosanol

Summary

Introduction

Brown adipose tissue (BAT) is an attractive therapeutic target for treating obesity and metabolic diseases. 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. Octacosanol and policosanol significantly increased the expression of Ffar[4], 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. These results suggest that octacosanol and policosanol ameliorate diet-induced obesity and metabolic disorders by increasing BAT activity and improving hepatic lipid metabolism These lipids represent promising therapeutic targets for the prevention and treatment of obesity and obesity-related metabolic disorders. Promoting the development and function of brown and beige fat appears as an attractive treatment for obesity and obesity-related metabolic diseases

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Conclusion