Comparative Effects and Mechanisms of Chitosan and Its Derivatives on Hypercholesterolemia in High-Fat Diet-Fed Rats.

Chen-Yuan Chiu,Shing-Hwa Liu,Tsai-En Yen,Meng-Tsan Chiang

doi:10.3390/ijms21010092

Abstract

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).

Highlights

The hepatic manifestation, non-alcoholic fatty liver disease (NAFLD), has been an emerging public concern worldwide with an estimated 20%~30% prevalence among developing and developed countries, which is associated with elevated mortality and morbidity, due to changing dietary habits in the consumption of western-style foods [1,2]
As well as the partial deacetylation of chitin composed of β-(1-4)-linked D-glucosamine and N-acetyl-d-glucosamine from the exoskeletons of marine crustaceans, including shrimps and crabs, has had its advantages manifested as the functional food used in the prevention or treatment of the aforementioned chronic diseases, containing antibacterial, antidiabetic, antioxidant, anticancer, anti-inflammatory, and hypocholesterolemic properties [8,9,10,11]
We examined the effects of high molecular weight chitosan (HC), low molecular weight chitosan (LC), and chitosan oligosaccharides (CO) on body weight, organ weights, and food intake in HF diet-fed rats

Summary

Introduction

The hepatic manifestation, non-alcoholic fatty liver disease (NAFLD), has been an emerging public concern worldwide with an estimated 20%~30% prevalence among developing and developed countries, which is associated with elevated mortality and morbidity, due to changing dietary habits in the consumption of western-style foods [1,2]. Hypercholesterolemia, a characteristic disorder of lipid metabolism that arose from overloads of cholesterol-, trans-fat-, and saturated fat-rich food, is a critical risk factor for the initiation and progression of NAFLD, leading to other chronic diseases, including cardiovascular diseases (CVD), metabolic syndrome, and cancer [3,4,5]. A remarkable number of natural bioactive products have been explored from various marine organisms for the prevention or therapy of chronic diseases, including cardiovascular diseases, diabetes, arthritis, osteoporosis, neurodegenerative diseases, acquired immunodeficiency syndrome (AIDS), and cancers [7]. In the present study, high-fat (HF) diet-induced hypercholesterolemic rats were used as a metabolic imbalance animal model to interpret the comparative effects and mechanisms among HC, LC, and CO groups in regulating blood, hepatic, or fecal cholesterol levels

Results and Discussion

Western Blot Analysis

Statistical Evaluation

Conclusions