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

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).

An inverse association of weight and the occurrence of asymptomatic gallbladder stone disease in hypercholesterolemia patients: a case-control study

“…This results in not maintaining reasonably high intake of monounsaturated fats and fiber, olive oil and fish (ω-3 fatty acids), vegetable protein, fruit, coffee, or vitamin C [7,51]. A recent study showed that a supplementation with 5% chitosan oligosaccharide, a common food additive for weight loss, may cause liver damage via higher hepatic cholesterol accumulation and higher intestinal cholesterol uptake in high fat diet-fed rats [52]. A carbohydrate-restricted, high-fat diet increased LDLcholesterol concentrations because this effect of weight loss was related to the lack of suppression of both fasting and 24-h free fatty acids [53].…”

An Inverse Association of Weight and the Occurrence of Asymptomatic Gallbladder Stone Disease in Hypercholesterolemia Patients in Northwest China: A Case-Control Study.

“…This results in not maintaining reasonably high intake of monounsaturated fats and ber, olive oil and sh (ω-3 fatty acids), vegetable protein, fruit, coffee, or vitamin C (7,48). A recent study showed that a supplementation with 5% chitosan oligosaccharide, a common food additive for weight loss, may cause liver damage via higher hepatic cholesterol accumulation and higher intestinal cholesterol uptake in high fat diet-fed rats (49). A carbohydrate-restricted, high-fat diet increased LDL-cholesterol concentrations because this effect of weight loss was related to the lack of suppression of both fasting and 24-h free fatty acids (50).…”

Tissue Integrity and COVID-19

“…Evidently now is the time for experimental and clinical confirmation of statins applicability in COVID-19 treatment [111]. It is well known that chitosan also can decrease the content of cholesterol [113]. Chitosan prevents cholesterol deposition into erythrocyte membranes [114].…”