The Regulatory Effect And Mechanism Of Cyclodextrins On The Homeostasis Of Glucolipid Metabolism In Mice

Homeostasis of glucolipid metabolism is an important guarantee for the body to cope with changes in physiological conditions and environmental factors.The imbalance of glucolipid metabolism can lead to the development of obesity,diabetes and other metabolic diseases,which seriously threaten human health.Therefore,searching for effective methods to regulate the homeostasis of glucolipid metabolism and exploring its mechanism have a guiding role in the prevention and intervention of metabolic diseases,and is also significant for promoting human health and reducing the burden on socioeconomic and health care systems.Cyclodextrins are cyclic oligosaccharides consisting of 6-8 or more Dglucopyranose units linked by α-1,4-glycosidic bonds.α-,β-and γ-cyclodextrins are commonly used as food additives.They are odorless and tasteless,which can not only promote intestinal health as prebiotics,but also form inclusion complexes with dietary fats and affect their digestion and absorption.Thus,cyclodextrins have a broad scope in regulating the homeostasis of glucolipid metabolism as well as preventing and intervening in metabolic diseases.Based on this,a high-fat diet-induced mouse model and a type II diabetic mouse model were constructed to evaluate the effects of dietary supplementation ofα-,β-and γ-cyclodextrins on the homeostasis of glucolipid metabolism.And the related mechanisms were also analyzed by measuring the expression of glucolipid metabolismrelated proteins,and sequencing intestinal microorganisms.The main results of the present study are as follows.Firstly,a high-fat diet-induced C57BL/6J mouse model was constructed to evaluate the effects of dietary supplementation of α-,β-and γ-cyclodextrins on lipid metabolism.The results showed that dietary supplementation of all three cyclodextrins reduced the ectopic deposition of fat in the liver and protected the function of brown adipose tissue in mice.Dietary supplementation of α-cyclodextrin promoted energy expenditure and enhanced the proportion of fatty acid oxidation for energy supply in mice.Dietary supplementation of β-cyclodextrin was effective in body weight control,with a 24.50% lower body weight gain.β-cyclodextrin also improved blood lipid levels.Compared with the control group,the serum TG and TC levels of mice in the β-cyclodextrin group were reduced by 16.50% and 23.61%(p<0.05),respectively.Dietary supplementation with γ-cyclodextrin significantly elevated the content of short-chain fatty acids in the cecum contents of mice,with a 1.44-fold increase in total short-chain fatty acid levels compared to the control group.Secondly,a normal diet db/db mouse model was constructed to evaluate the effects of dietary supplementation of cyclodextrins on the glucolipid metabolism in type II diabetic mice.The results indicated that dietary supplementation of all three cyclodextrins could delay the development of diabetic nephropathy in type II diabetic mice.Dietary supplementation of β-cyclodextrin reduced the peak postprandial glucose by 25.67% and the AUC of the OGTT curve by 58.83%(p<0.05),which significantly improved the impairment of glucose tolerance and glucose metabolism,reduced insulin resistance and protected islet function.Dietary supplementation of β-cyclodextrin and γ-cyclodextrin could alleviate liver steatosis in type II diabetic mice.Dietary supplementation of β-cyclodextrin could improve blood lipid parameters and reduce the risk of cardiovascular disease in type II diabetic mice.Finally,the mechanisms of dietary supplementation of cyclodextrins in regulating the homeostasis of body glycolipid metabolism were further analyzed.The results revealed that all three cyclodextrins significantly increased PPARα levels and decreased SREBP-1c,PEPCK and G-6-PC levels in mice liver tissues,and affected glucolipid metabolic homeostasis by inhibiting adipose de novo synthesis,enhancing fatty acid β-oxidation and inhibiting gluconeogenesis.The effect of cyclodextrins in maintaining homeostasis of glucolipid metabolism was related to the regulation of intestinal microorganisms.Dietary supplementation of three cyclodextrins significantly elevated the relative abundance of Lactobacillus and Akkermansia in high-fat diet-induced C57BL/6J mouse model.Akkermansia was identified as an α-cyclodextrin group biomarker,and Coprococcus and Butyricicoccus were identified as γ-cyclodextrin group biomarkers.Akkermansia and Bifidobacterium were identified as β-cyclodextrin group biomarkers in normal diet db/db mouse model.