Ezetimibe reduced hepatic steatosis induced by dietary oxysterols in nonhuman primates. Issue 10 (20th September 2016)

• Record Type: Journal Article
• Authors: Deushi, Michiyo; Osaka, Mizuko; Nakano, Kaku; Osada, Kyoichi; Egashira, Kensuke; Yoshida, Masayuki
• Is Part Of: FEBS open bio. Volume 6:Issue 10(2016)
• Page Start: 1008
• Page End: 1015
• Publication Date: 2016-09-20
• Subjects: dietary oxysterols -- ezetimibe -- Niemann–Pick C1‐like1 -- nonalcoholic fatty liver disease -- nonhuman primate -- steatosis; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.12107
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : Oxidized cholesterol (oxysterols) plays an important and multifaceted role in lipid metabolism. Here we examined whether dietary oxysterols accelerate hepatic lipid accumulation and inflammation in nonhuman primates. We also examined the effect of the Niemann–Pick C1‐like1 inhibitor, ezetimibe (Ez). Macaca fascicularis (5‐year‐old males) were fed either regular cholesterol + high‐fat diet (control‐HFD) or oxysterols + high‐fat diet (ox‐HFD; with 0.015% of oxysterols cholesterol) for 24 weeks. Compared with control‐HFD, ox‐HFD did not affect plasma lipid levels, but it did affect hepatic lipid levels [total cholesterol, 40.9 mg·g −1 (ox‐HFD) versus 3.2 (control‐HFD) mg·g −1 ; triglycerides, 28.0 (ox‐HFD) versus 5.7 (control‐HFD) mg·g −1 ]. Ox‐HFD increased lipid accumulation as well as recruitment of inflammatory cells when compared to control‐HFD. We then examined the effects of Ez, 0.2 mg·kg −1 ·day −1 for 12 weeks. In addition to a significant reduction in dyslipidemia, Ez alleviated biochemical and pathological aspects of steatosis. Dietary oxysterols aggravate steatosis in nonhuman primates. Treatment with Ez may be a novel therapeutic approach to NAFLD by alleviating dyslipidemia. Abstract : Dietary oxysterols combined with a high‐fat diet raised lipid levels in the liver but not plasma in nonhuman primates. Ezetimibe, a Niemann–Pick C1‐like1 inhibitor, improves oxysterol‐induced hepatic steatosis and associated leukocyte activation. The potential effect of ezetimibe may involve altering the balance of inflammatory cytokines.