Dataset Information

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

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.

SUBMITTER: Sharma R

PROVIDER: S-EPMC6435753 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Sharma Rahul R Sharma Rahul R Matsuzaka Takashi T Kaushik Mahesh K MK Sugasawa Takehito T Ohno Hiroshi H Wang Yunong Y Motomura Kaori K Shimura Takuya T Okajima Yuka Y Mizunoe Yuhei Y Ma Yang Y Saber Zahara M ZM Iwasaki Hitoshi H Yatoh Shigeru S Suzuki Hiroaki H Aita Yuichi Y Han Song-Iee SI Takeuchi Yoshinori Y Yahagi Naoya N Miyamoto Takafumi T Sekiya Motohiro M Nakagawa Yoshimi Y Shimano Hitoshi H

Scientific reports 20190326 1

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 weigh ...[more]

PMID: 30914769

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Project description:Background/aimsBrown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone Morphogenetic Protein 7 (BMP7) was identified as an inducer of BAT differentiation. We aimed to elucidate the role of sympathetic activation in the effect of BMP7 on BAT by treating mice with BMP7 at varying ambient temperature, and assessed the therapeutic potential of BMP7 in combating obesity.Methods and resultsHigh-fat diet fed lean C57Bl6/J mice were treated with BMP7 via subcutaneous osmotic minipumps for 4 weeks at 21 °C or 28 °C, the latter being a thermoneutral temperature in which sympathetic activation of BAT is largely diminished. At 21 °C, BMP7 increased BAT weight, increased the expression of Ucp1, Cd36 and hormone-sensitive lipase in BAT, and increased total energy expenditure. BMP7 treatment markedly increased food intake without affecting physical activity. Despite that, BMP7 diminished white adipose tissue (WAT) mass, accompanied by increased expression of genes related to intracellular lipolysis in WAT. All these effects were blunted at 28 °C. Additionally, BMP7 resulted in extensive 'browning' of WAT, as evidenced by increased expression of BAT markers and the appearance of whole clusters of brown adipocytes via immunohistochemistry, independent of environmental temperature. Treatment of diet-induced obese C57Bl6/J mice with BMP7 led to an improved metabolic phenotype, consisting of a decreased fat mass and liver lipids as well as attenuated dyslipidemia and hyperglycemia.ConclusionTogether, these data show that BMP7-mediated recruitment and activation of BAT only occurs at subthermoneutral temperature, and is thus likely dependent on sympathetic activation of BAT, and that BMP7 may be a promising tool to combat obesity and associated disorders.

Dataset Information

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

Publications

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

Similar Datasets

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