https://scholars.lib.ntu.edu.tw/handle/123456789/567448
標題: | Comparative effects and mechanisms of chitosan and its derivatives on hypercholesterolemia in high-fat diet-fed rats | 作者: | Chiu C.-Y. Yen T.-E. SHING-HWA LIU Chiang M.-T. |
關鍵字: | Chitosan oligosaccharide; High and low molecular weight chitosan; Lipid metabolism | 公開日期: | 2020 | 出版社: | MDPI AG | 卷: | 21 | 期: | 1 | 來源出版物: | International Journal of Molecular Sciences | 摘要: | The present study investigated and compared the effects of different molecular weights of chitosan (high molecular weight chitosan (HC) and low molecular weight chitosan (LC)) and its derivatives (chitosan oligosaccharide (CO)) on cholesterol regulation in high-fat (HF) diet-fed rats. A diet supplementation of 5% HC, 5% LC, or 5% CO for 8 weeks showed hypocholesterolemic potential in HF diet-fed rats. Unexpectedly, a 5% CO-supplemented diet exerted hepatic damage, producing increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor-alpha (TNF-α). The supplementation of HC and LC, unlike CO, significantly decreased the hepatic total cholesterol (TC) levels and increased the fecal TC levels in HF diet-fed rats. The hepatic protein expression of the peroxisome proliferator-activated receptor-α (PPARα) in the HF diet-fed rats was markedly decreased, which could be significantly reversed by both HC and LC, but not CO, supplementation. Unlike the supplementation of CO, both HC and LC supplementation could effectively reverse the HF-inhibited/induced gene expressions of the low-density lipoprotein receptor (LDLR) and cholesterol 7α-hydroxylase (CYP7A1), respectively. The upregulated intestinal acyl-CoA cholesterol acyltransferase 2 (ACAT2) protein expression in HF diet-fed rats could be reversed by HC and LC, but not CO, supplementation. Taken together, a supplementation of 5% CO in HF diet-fed rats may exert liver damage via a higher hepatic cholesterol accumulation and a higher intestinal cholesterol uptake. Both HC and LC effectively ameliorated the hypercholesterolemia and regulated cholesterol homeostasis via the activation and inhibition of hepatic (AMPKα and PPARα) and intestinal (ACAT2) cholesterol-modulators, respectively, as well as the modulation of downstream signals (LDLR and CYP7A1). ? 2019 by the authors. Licensee MDPI, Basel, Switzerland. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85076900044&doi=10.3390%2fijms21010092&partnerID=40&md5=d2e02a95ec889d7ddd57beefbf48e9e6 https://scholars.lib.ntu.edu.tw/handle/123456789/567448 |
ISSN: | 1661-6596 | DOI: | 10.3390/ijms21010092 | SDG/關鍵字: | alanine aminotransferase; aspartate aminotransferase; chitosan; chitosan derivative; chitosan oligosaccharide; cholesterol; cholesterol 7alpha monooxygenase; cholesterol acyltransferase; cholesterol acyltransferase 2; high density lipoprotein cholesterol; high molecular weight chitosan; hydroxymethylglutaryl coenzyme A reductase kinase; hydroxymethylglutaryl coenzyme A reductase kinase alpha; low density lipoprotein cholesterol; low molecular weight chitosan; peroxisome proliferator activated receptor alpha; tumor necrosis factor; unclassified drug; very low density lipoprotein cholesterol; alanine aminotransferase; aspartate aminotransferase; chitosan; cholesterol; cholesterol 7alpha monooxygenase; cholesterol acyltransferase; CYP7A1 protein, rat; peroxisome proliferator activated receptor alpha; sterol O-acyltransferase 2; tumor necrosis factor; animal experiment; animal model; animal tissue; Article; body weight gain; cholesterol transport; controlled study; diet supplementation; down regulation; Fourier transform infrared spectroscopy; gene expression; hepatitis; high performance liquid chromatography; hypercholesterolemia; lipid diet; lipid homeostasis; lipid metabolism; liver injury; liver weight; male; nonalcoholic fatty liver; nonhuman; protein expression; radioimmunoprecipitation; rat; real time reverse transcription polymerase chain reaction; reverse transcription polymerase chain reaction; RNA extraction; upregulation; Western blotting; adverse event; animal; drug effect; hypercholesterolemia; lipid diet; liver; metabolism; Sprague Dawley rat; Alanine Transaminase; Animals; Aspartate Aminotransferases; Chitosan; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Diet, High-Fat; Hypercholesterolemia; Liver; Male; PPAR alpha; Rats; Rats, Sprague-Dawley; Sterol O-Acyltransferase; Tumor Necrosis Factor-alpha |
顯示於: | 毒理學研究所 |
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