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Ezetimibe prevents the development of non‑alcoholic fatty liver disease induced by high‑fat diet in C57BL/6J mice.

Wang X, Ren Q, Wu T, Guo Y, Liang Y, Liu S - Mol Med Rep (2014)

Bottom Line: Administration of ezetimibe significantly reduced liver steatosis and fibrosis.Furthermore, ezetimibe significantly reduced hepatic mRNA expression of Acc1 and Scd1, which are involved in hepatic fatty acid synthesis.Ezetimibe significantly reduced hepatic Cd36 gene expression, upregulation of which is significantly associated with insulin resistance, hyperinsulinemia and increased steatosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology and Metabolism, The First Hospital of Shijiazhuang City, Shijiazhuang, Hebei 050011, P.R. China.

ABSTRACT
There is currently no established treatment for non‑alcoholic fatty liver disease (NAFLD), including its most extreme form, non‑alcoholic steatohepatitis (NASH). Ezetimibe, an inhibitor of Niemann‑Pick C1 Like 1‑dependent cholesterol absorption, improves diet‑induced hyperlipidemia and attenuates liver steatosis and insulin resistance. The aim of the present study was to determine whether ezetimibe treatment is able to inhibit the development of NAFLD, and to elucidate the underlying mechanism, using C57BL/6J (B6) mice maintained on a high‑fat diet. Male B6 mice (20 weeks of age) were divided into the following two groups (n=7 in each group): Mice fed a high‑fat diet for four weeks and mice fed a high‑fat diet with 0.0064% (wt/wt) ezetimibe (5 mg/kg/day) for four weeks. Administration of ezetimibe significantly reduced liver steatosis and fibrosis. Ezetimibe reduced serum cholesterol, hepatic fat accumulation and insulin resistance in the liver of mice fed the high‑fat diet. Furthermore, ezetimibe significantly reduced hepatic mRNA expression of Acc1 and Scd1, which are involved in hepatic fatty acid synthesis. Ezetimibe significantly reduced hepatic Cd36 gene expression, upregulation of which is significantly associated with insulin resistance, hyperinsulinemia and increased steatosis. The protein expression of SKP2, a viable therapeutic target in human cancer, was also reduced by ezetimibe. These findings suggest that ezetimibe may be an effective therapy for high fat‑induced NAFLD, including NASH.

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Related in: MedlinePlus

Food consumption and body weight variation of C57BL/6J mice fed high-fat chow. Variations in (A) body weight and (B) food consumption. White squares, mice fed high-fat chow; black circles, mice fed high-fat chow plus ezetimibe. The data are expressed as the means ± standard deviation (n=7). **P<0.01, vs. HF group. W, week.
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f2-mmr-10-06-2917: Food consumption and body weight variation of C57BL/6J mice fed high-fat chow. Variations in (A) body weight and (B) food consumption. White squares, mice fed high-fat chow; black circles, mice fed high-fat chow plus ezetimibe. The data are expressed as the means ± standard deviation (n=7). **P<0.01, vs. HF group. W, week.

Mentions: The livers of HF mice were markedly enlarged and exhibited a paler color as compared with the livers of the HF+EZ group (Fig. 1, Table I) The food consumption and body weight of the two groups were monitored throughout the observation period. Although the baseline body weight was similar between the two groups (Table I, Fig 2A), the body weight was significantly lower in the HF+EZ group as compared with the HF group during weeks 1–4 following ezetimibe treatment (P<0.01; Fig. 2A). Food consumption was similar between HF and HF+EZ groups (Fig. 2B). The final body and liver weights were significantly lower in the HF+EZ group than in the HF group (P<0.01; Table I). Liver TG content was significantly lower in the HF+EZ group, as compared with that of the HF group (P<0.05; Table I).


Ezetimibe prevents the development of non‑alcoholic fatty liver disease induced by high‑fat diet in C57BL/6J mice.

Wang X, Ren Q, Wu T, Guo Y, Liang Y, Liu S - Mol Med Rep (2014)

Food consumption and body weight variation of C57BL/6J mice fed high-fat chow. Variations in (A) body weight and (B) food consumption. White squares, mice fed high-fat chow; black circles, mice fed high-fat chow plus ezetimibe. The data are expressed as the means ± standard deviation (n=7). **P<0.01, vs. HF group. W, week.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4227427&req=5

f2-mmr-10-06-2917: Food consumption and body weight variation of C57BL/6J mice fed high-fat chow. Variations in (A) body weight and (B) food consumption. White squares, mice fed high-fat chow; black circles, mice fed high-fat chow plus ezetimibe. The data are expressed as the means ± standard deviation (n=7). **P<0.01, vs. HF group. W, week.
Mentions: The livers of HF mice were markedly enlarged and exhibited a paler color as compared with the livers of the HF+EZ group (Fig. 1, Table I) The food consumption and body weight of the two groups were monitored throughout the observation period. Although the baseline body weight was similar between the two groups (Table I, Fig 2A), the body weight was significantly lower in the HF+EZ group as compared with the HF group during weeks 1–4 following ezetimibe treatment (P<0.01; Fig. 2A). Food consumption was similar between HF and HF+EZ groups (Fig. 2B). The final body and liver weights were significantly lower in the HF+EZ group than in the HF group (P<0.01; Table I). Liver TG content was significantly lower in the HF+EZ group, as compared with that of the HF group (P<0.05; Table I).

Bottom Line: Administration of ezetimibe significantly reduced liver steatosis and fibrosis.Furthermore, ezetimibe significantly reduced hepatic mRNA expression of Acc1 and Scd1, which are involved in hepatic fatty acid synthesis.Ezetimibe significantly reduced hepatic Cd36 gene expression, upregulation of which is significantly associated with insulin resistance, hyperinsulinemia and increased steatosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology and Metabolism, The First Hospital of Shijiazhuang City, Shijiazhuang, Hebei 050011, P.R. China.

ABSTRACT
There is currently no established treatment for non‑alcoholic fatty liver disease (NAFLD), including its most extreme form, non‑alcoholic steatohepatitis (NASH). Ezetimibe, an inhibitor of Niemann‑Pick C1 Like 1‑dependent cholesterol absorption, improves diet‑induced hyperlipidemia and attenuates liver steatosis and insulin resistance. The aim of the present study was to determine whether ezetimibe treatment is able to inhibit the development of NAFLD, and to elucidate the underlying mechanism, using C57BL/6J (B6) mice maintained on a high‑fat diet. Male B6 mice (20 weeks of age) were divided into the following two groups (n=7 in each group): Mice fed a high‑fat diet for four weeks and mice fed a high‑fat diet with 0.0064% (wt/wt) ezetimibe (5 mg/kg/day) for four weeks. Administration of ezetimibe significantly reduced liver steatosis and fibrosis. Ezetimibe reduced serum cholesterol, hepatic fat accumulation and insulin resistance in the liver of mice fed the high‑fat diet. Furthermore, ezetimibe significantly reduced hepatic mRNA expression of Acc1 and Scd1, which are involved in hepatic fatty acid synthesis. Ezetimibe significantly reduced hepatic Cd36 gene expression, upregulation of which is significantly associated with insulin resistance, hyperinsulinemia and increased steatosis. The protein expression of SKP2, a viable therapeutic target in human cancer, was also reduced by ezetimibe. These findings suggest that ezetimibe may be an effective therapy for high fat‑induced NAFLD, including NASH.

Show MeSH
Related in: MedlinePlus