Effects and Mechanisms of Chitosan and ChitosanOligosaccharide on Hepatic Lipogenesis and Lipid Peroxidation, Adipose Lipolysis, and Intestinal Lipid Absorption in Rats with High-Fat Diet-Induced Obesity

Abstract

Chitosan and its derivative, chitosan oligosaccharide (CO), possess hypolipidemic and anti-obesity effects. However, it is still unclear if the mechanisms are different or similar between chitosan and CO. This study was designed to investigate and compare the effects of CO and high-molecular-weight chitosan (HC) on liver lipogenesis and lipid peroxidation, adipose lipolysis, and intestinal lipid absorption in high-fat (HF) diet-fed rats for 12 weeks. Rats were divided into four groups: normal control diet (NC), HF diet, HF diet+5% HC, and HF diet+5% CO. Both HC and CO supplementation could reduce liver lipid biosynthesis, but HC had a better effect than CO on improving liver lipid accumulation in HF diet-fed rats. The increased levels of triglyceride decreased lipolysis rate, and increased lipoprotein lipase activity in the perirenal adipose tissue of HF diet-fed rats could be significantly reversed by both HC and CO supplementation. HC, but not CO, supplementation promoted liver antioxidant enzymes glutathione peroxidase and superoxide dismutase activities and reduced liver lipid peroxidation. In the intestines, CO, but not HC, supplementation reduced lipid absorption by reducing the expression of fabp2 and fatp4 mRNA. These results suggest that HC and CO have different mechanisms for improving lipid metabolism in HF diet-fed rats.

Keywords: chitosan oligosaccharide; high-fat diet-fed rats; high-molecular-weight chitosan; lipid metabolism.

Figure 1

The changes in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in rats fed with different experimental diets after 12 weeks. Data are expressed as the mean ± S.D. for each group (n = 8). Values with different superscript letters (a, b) are significantly different from each other (p < 0.05). NC: Normal control diet (chow diet). HF: High-fat diet (chow diet + 10% lard). HC: HF diet + 5% high-molecular-weight chitosan. CO: HF diet + 5% chitosan oligosaccharides.

Figure 2

The changes in liver histological morphology in rats fed with different experimental diets for 12 weeks. (A) Liver tissue sections were stained with hematoxylin and eosin (H&E) staining. (B) Data are expressed as the mean ± S.D. for each group (n = 8). Values with different superscript letters (a, b, c) are significantly different from each other (p < 0.05). NC: Normal control diet (chow diet). HF: High-fat diet (chow diet + 10% lard). HC: HF diet + 5% high-molecular-weight chitosan. CO: HF diet + 5% chitosan oligosaccharides.

Figure 3

The changes in hepatic phosphorylated AMPKα. AMPKα (A), and PPAR-γ (B) protein expression in rats fed with different experimental diets for 12 weeks. Protein expression for pAMPKα, AMPKα, and PPAR-γ was determined by Western blotting. Densitometric analysis for protein levels corrected to each internal control was shown. Data are expressed as the mean ± S.D. for each group (n = 4–5). Values with different superscript letters (a, b, c) are significantly different from each other (p < 0.05). NC: Normal control diet (chow diet). HF: High-fat diet (chow diet + 10% lard). HC: HF diet + 5% high-molecular-weight chitosan. CO: HF diet + 5% chitosan oligosaccharides.

Figure 4

The changes in hepatic thiobarbituric acid reactive substances (TBARS) levels (A) and antioxidative enzymes (glutathione peroxidase (GPx) (B) and superoxide dismutase (SOD) (C) activities in rats fed with different experimental diets for 12 weeks. Data are expressed as the mean ± S.D. for each group (n = 8). Values with different superscript letters (a, b) are significantly different from each other (p < 0.05). NC: Normal control diet (chow diet). HF: High-fat diet (chow diet + 10% lard). HC: HF diet + 5% high-molecular-weight chitosan. CO: HF diet + 5% chitosan oligosaccharides.

Figure 5

The changes in hepatic immunohistochemical staining for 4-hydroxy-2-nonenal (4-HNE) in rats fed with different experimental diets for 12 weeks. (A) Liver sections were immunohistochemically stained with 4-HNE. (B) Data are expressed as the mean ± S.D. for each group (n = 8). Values with different superscript letters (a, b, c) are significantly different from each other (p < 0.05). NC: Normal control diet (chow diet). HF: High-fat diet (chow diet + 10% lard). HC: HF diet + 5% high-molecular-weight chitosan. CO: HF diet + 5% chitosan oligosaccharides.

Figure 6

The changes in triglyceride level (A), lipolysis rate (B), and lipoprotein lipase (LPL) activity (C) in the perirenal adipose tissue of rats fed with different experimental diets for 12 weeks. Data are expressed as the mean ± S.D. for each group (n = 8). Values with different superscript letters (a, b) are significantly different from each other (p < 0.05). NC: Normal control diet (chow diet). HF: High-fat diet (chow diet + 10% lard). HC: HF diet + 5% high-molecular-weight chitosan. CO: HF diet + 5% chitosan oligosaccharides.

Figure 7

The changes in intestinal fabp2 (A) and fatp4 (B) mRNA expression in rats fed with different experimental diets for 12 weeks. Data are expressed as the mean ± S.D. for each group (n = 6). Values with different superscript letters (a, b, c) are significantly different from each other (p < 0.05). NC: Normal control diet (chow diet). HF: High-fat diet (chow diet + 10% lard). HC: HF diet + 5% high-molecular-weight chitosan. CO: HF diet + 5% chitosan oligosaccharides.