O-Carboxymethyl chitosan (O-CMCs) and N-((2-hydroxy-3-N,N-dimethylhexadecylammonium)propyl)chitosan chloride (N-CQCs) were synthesized for nonalcoholic fatty liver disease (NAFLD) treatment. The weight-average weight and substitution degree of O-CMCs and N-CQCs were 6.5 × 10(4) and 0.72 and 7.9 × 10(4) and 0.21, respectively. O-CMCs was negatively charged with a zeta-potential value of -31.82 mV, whereas that of N-CQCs was +36.1 mV, and both showed low cytotoxcity. Serum lipid level and liver fat accumulation were reduced with chitosan and its two derivatives. Furthermore, mRNA and protein expression assay of hepatic lipid metabolism enzymes and low-density lipoprotein receptor (LDL-R) were observed by RT-PCR and Western blot. Results showed that N-CQCs exhibited a more evident desired effect than chitosan and O-CMCs, indicating that amphiphilicity, solubility, and surface charge of chitosan and its two derivatives played roles in the expression of hepatic lipid metabolism enzymes and LDL-R. Therefore, dietary supplementation of O-CMCs and N-CQCs can alleviate the high fat diet induced aberrations related to NAFLD by their antilipidemic property.
Owing to their distinct biochemical properties, chitosan and its derivatives have a great potential in a range of bioapplications. One such application is as a dietary antilipidemic supplement to be used in reducing obesity and to improve insulin resistance. The lipid-binding efficiency of chitosan and its derivatives, however, remains debatable. Accordingly, in this study we investigated the interaction of chitosan and its two derivatives, O-carboxymethyl chitosan (O-CMCs) and N-[(2-hydroxy-3-N,N-dimethylhexadecyl ammonium)propyl]chitosan chloride (N-CQCs), with plasma leptin, glucose, insulin and total cholesterol in a diet-induced insulin-resistant rat model, and further interaction with mRNA expression of adipocytokines and its related molecule PPAR-γ. The experiments were performed using the RT-PCR technique in cultured 3T3-L1 adipocytes, in which the mRNA expression of leptin, adiponectin, resistin and PPAR-γ was recorded in the absence and presence of chitosan, O-CMCs and N-CQCs. The experimental results proved that chitosan, O-CMCs and N-CQCs not only lowered the level of plasma leptin, glucose, insulin and total cholesterol in vivo, but down-regulated mRNA expression of leptin and resistin, and up-regulated mRNA expression of adiponectin and PPAR-γ in vitro, to achieve the desired insulin resistance therapy.
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