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. 2019 Mar 26;9(1):5169.
doi: 10.1038/s41598-019-41631-1.

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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Free PMC article

Octacosanol and Policosanol Prevent High-Fat Diet-Induced Obesity and Metabolic Disorders by Activating Brown Adipose Tissue and Improving Liver Metabolism

Rahul Sharma et al. Sci Rep. .
Free PMC article

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.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Effect of octacosanol and policosanol on body weight, body composition and fat accumulation in mice fed on chow, high fat diet (HFD) and HFD treated with octacosanol or policosanol. (a,b) Body weight (a) and body weight gain (b) of mice fed on chow, HFD and HFD treated with octacosanol or policosanol (60 mg/kg/day) for four weeks (n = 7–8). (ce) Changes in fat mass (c), lean mass (d) and percent fat (e) measured by dual-energy X-ray absorptiometry (DEXA) analysis (n = 5). (fh) Weight of epididymal white adipose tissue (eWAT) (f), inguinal WAT (iWAT) (g), brown adipose tissue (BAT) (h) of mice fed on chow, HFD and HFD treated with octacosanol or policosanol for four weeks (n = 7–8). Values represent mean ± standard error of mean (SEM). *P < 0.05, **P < 0.01, ***P < 0.001 by using one-way ANOVA followed by scheffe post hoc test.
Figure 2
Figure 2
Effect of octacosanol and policosanol on plasma metabolic parameters of mice fed on chow, HFD and HFD treated with octacosanol or policosanol. (ae) Concentrations of blood glucose (a), plasma insulin (b), plasma triglycerides (TGs) (c), plasma total cholesterol (TC) (d) and plasma free fatty acids (FFA) (e) of mice fed on chow, HFD and HFD treated with octacosanol or policosanol for four weeks (n = 5). Values represent mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 by using one-way ANOVA followed by scheffe post hoc test.
Figure 3
Figure 3
Effect of octacosanol and policosanol on brown adipose tissue (BAT) of mice fed on chow, HFD and HFD treated with octacosanol or policosanol. (a) Representative hematoxylin and eosin (H&E)-stained sections of BAT harvested from mice fed on chow, HFD and HFD treated with octacosanol or policosanol for four weeks. (b) Western blotting of UCP-1 and GAPDH in BAT (n = 5). GAPDH was used as a loading control. (c) Protein expression of UCP-1 determined by densitometry analysis (n = 5). (d) Quantitative real-time PCR (qRT-PCR) analysis of genes involved in thermogenesis of BAT in mice fed on chow, HFD and HFD treated with octacosanol or policosanol for four weeks (n = 5–8). (e) Rectal temperature of mice fed on chow, HFD and HFD treated with octacosanol or policosanol for four weeks (n = 5). Values represent mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 by using one-way ANOVA followed by scheffe post hoc test.
Figure 4
Figure 4
Effect of octacosanol and policosanol on inguinal white adipose tissue (iWAT) of mice fed on chow, HFD and HFD treated with octacosanol or policosanol. (a) Representative H&E-stained sections of iWAT harvested from mice fed on chow, HFD and HFD treated with octacosanol or policosanol for four weeks. Scale bar = 30 μm. (b) Average adipocyte size in iWAT of mice fed on chow, HFD and HFD treated with octacosanol or policosanol for four weeks (n = 5). (c) qRT-PCR analysis of beige fat markers in iWAT harvested from mice fed on chow, HFD and HFD treated with octacosanol or policosanol for four weeks (n = 5–8). (d) Western blotting of UCP-1 and GAPDH in iWAT (n = 4–5). GAPDH was used as a loading control. (e) Protein expression of UCP-1 determined by densitometry analysis (n = 4–5). Values represent mean ± SEM *P < 0.05, **P < 0.01, ***P < 0.001 by using one-way ANOVA followed by scheffe post hoc test.
Figure 5
Figure 5
Effect of octacosanol and policosanol on epididymal WAT (eWAT) of mice fed on chow, HFD and HFD treated with octacosanol or policosanol. (a) Representative H&E-stained sections of eWAT harvested from mice fed on chow, HFD and HFD treated with octacosanol or policosanol for four weeks. Scale bar = 30 μm. (b) Average adipocyte size in eWAT of mice fed on chow, HFD and HFD treated with octacosanol or policosanol for four weeks (n = 5). (c) Representative immunohistochemical staining for CD68 in eWAT sections of mice fed on chow, HFD and HFD treated with octacosanol or policosanol for four weeks. (d) qRT-PCR analysis of genes involved in the inflammation of iWAT harvested from mice fed on chow, HFD and HFD treated with octacosanol or policosanol for four weeks (n = 5). Values represent mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 by using one-way ANOVA followed by scheffe post hoc test.
Figure 6
Figure 6
Effect of octacosanol and policosanol on the liver ofmice fed on chow, HFD and HFD treated with octacosanol or policosanol. (ac) Liver weight (a) and hepatic levels of TG (b) and TC (c) in mice fed on chow, HFD and HFD treated with octacosanol or policosanol for four weeks (n = 5–8). (d,e) qRT-PCR analysis of genes involved in fatty acid (FA) metabolism (d) and cholesterol biosynthesis (e) in livers harvested from mice fed on chow, HFD and HFD treated with octacosanol or policosanol for four weeks (n = 5). Values represent mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 by using one-way ANOVA followed by scheffe post hoc test.
Figure 7
Figure 7
Effect of octacosanol on gene expression in BAT and iWAT harvested from mice fed a chow diet. (a,b) qRT-PCR analysis of genes involved in thermogenesis and energy expenditure of BAT (a) and iWAT (b) in mice fed on chow, with or without octacosanol treatment, for seven days (n = 5). Values represent mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 vs. control (vehicle-treated) mice by using student-t-test.

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