The present study examined and compared the effects of low- and high-molecular weight (MW) chitosan, a nutraceutical, on lipid metabolism in the intestine and liver of high-fat (HF) diet-fed rats. High-MW chitosan as well as low-MW chitosan decreased liver weight, elongated the small intestine, improved the dysregulation of blood lipids and liver fat accumulation, and increased fecal lipid excretion in rats fed with HF diets. Supplementation of both high- and low-MW chitosan markedly inhibited the suppressed phosphorylated adenosine monophosphate (AMP)-activated protein kinase-α (AMPKα) and peroxisome proliferator-activated receptor-α (PPARα) protein expressions, and the increased lipogenesis/cholesterogenesis-associated protein expressions [peroxisome proliferator-activated receptor-γ (PPARγ), sterol regulatory element binding protein-1c and -2 (SREBP1c and SREBP2)] and the suppressed apolipoprotein E (ApoE) and microsomal triglyceride transfer protein (MTTP) protein expressions in the livers of rats fed with HF diets. Supplementation with both a low- and high-MW chitosan could also suppress the increased MTTP protein expression and the decreased angiopoietin-like protein-4 (Angptl4) expression in the intestines of rats fed with HF diets. In comparison between low- and high-MW chitosan, high-MW chitosan exhibits a higher efficiency than low-MW chitosan on the inhibition of intestinal lipid absorption and an increase of hepatic fatty acid oxidation, which can improve liver lipid biosynthesis and accumulation.
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