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Ezetimibe reduced hepatic steatosis induced by dietary oxysterols in nonhuman primates

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)....

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Autores principales: Deushi, Michiyo, Osaka, Mizuko, Nakano, Kaku, Osada, Kyoichi, Egashira, Kensuke, Yoshida, Masayuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055037/
https://www.ncbi.nlm.nih.gov/pubmed/27761360
http://dx.doi.org/10.1002/2211-5463.12107
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author Deushi, Michiyo
Osaka, Mizuko
Nakano, Kaku
Osada, Kyoichi
Egashira, Kensuke
Yoshida, Masayuki
author_facet Deushi, Michiyo
Osaka, Mizuko
Nakano, Kaku
Osada, Kyoichi
Egashira, Kensuke
Yoshida, Masayuki
author_sort Deushi, Michiyo
collection PubMed
description 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.
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spelling pubmed-50550372016-10-19 Ezetimibe reduced hepatic steatosis induced by dietary oxysterols in nonhuman primates Deushi, Michiyo Osaka, Mizuko Nakano, Kaku Osada, Kyoichi Egashira, Kensuke Yoshida, Masayuki FEBS Open Bio Research Articles 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. John Wiley and Sons Inc. 2016-09-20 /pmc/articles/PMC5055037/ /pubmed/27761360 http://dx.doi.org/10.1002/2211-5463.12107 Text en © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Deushi, Michiyo
Osaka, Mizuko
Nakano, Kaku
Osada, Kyoichi
Egashira, Kensuke
Yoshida, Masayuki
Ezetimibe reduced hepatic steatosis induced by dietary oxysterols in nonhuman primates
title Ezetimibe reduced hepatic steatosis induced by dietary oxysterols in nonhuman primates
title_full Ezetimibe reduced hepatic steatosis induced by dietary oxysterols in nonhuman primates
title_fullStr Ezetimibe reduced hepatic steatosis induced by dietary oxysterols in nonhuman primates
title_full_unstemmed Ezetimibe reduced hepatic steatosis induced by dietary oxysterols in nonhuman primates
title_short Ezetimibe reduced hepatic steatosis induced by dietary oxysterols in nonhuman primates
title_sort ezetimibe reduced hepatic steatosis induced by dietary oxysterols in nonhuman primates
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055037/
https://www.ncbi.nlm.nih.gov/pubmed/27761360
http://dx.doi.org/10.1002/2211-5463.12107
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