Effects Of Fish Collagen Peptides On Lipid Metabolism In Mice Fed With High-fat Diet

Objective:obesity and lipid metabolism disorder are results from abnormal operation of multi-metabolic systems caused by high-fat diet（HFD）induced oxidative stress（OS）.Collagen peptides show improvements on obesity and OS in animals fed with HFD,while there is no in-depth study on the mechanisms yet.This issue was aimed to investigate the effects and mechanisms of fish collagen peptides（FCPs）on lipid metabolism in mice fed with HFD.Methods:male C57BL/6 mice（4 weeks old）were randomly divided into three groups（18 animals per group）by body mass,named as control normal diet group（CON）,HFD group（HF）and HFD+1%FCPs group（PHF）,respectively.Body mass,average daily feed intake and fat apparent digestion were recorded.The metabolic status of each group was monitrored by CLAMS.At the end of the 11th and 22th week,each group was randomly dimidiated by body weight and sacrificed with 8-hours fasting,respectively.Liver morphological analysis was determined by microscopy.Hepatic and plasma lipid profiles,redox status were examined.The mRNA expressions of key regulators of hepatic lipid metabolism were analyzed by qRT-PCR.Levels of thyroid hormones and the mRNA expressions of key regulators of thyroid secretion were examined.Endogenous H₂S level and its key regulators were analzed.Finally,metabonomics technique was utilized to verify the preceding results and indicate other potential mechanisms of FCPs.Results:after the 11-week’s feeding,in comparison to CON group,HF group showed significantly increased levels of body mass,liver and plasma lipid profiles with obviously OS.The mRNA expression levels of key regulators of hepatic lipogenesis and lipolysis were markedly increased and decreased,respectively.Meanwhile,the levels of thyroid hormones were significantly increased,and the mRNA expression levels of key regulators of thyroid secretion were markedly decreased.Compared with HF group,PHF group indicated significantly reduction of hepatic dipose vacuoles and plasma T4 level.Futhermore,increasing levels of liver GSH-Px activity,ratio of GSH/GSSG,endogenous H₂S and plasma HDL-C were observed in PHF group.After the 22-week’s feeding,the disorder of lipid metabolism was aggravated in HF group with turbulence of thyroid hormones levels and decreasing level of endogenous H₂S.In comparison of HF group,PHF group showed a strikingly increasing level of basic metabolism,while the lipid cumulation was significantly improved.The levels of hepatic TG,FFAand plasma TG,TC were markedly decreased with increased levels of HDL-C in liver.The mRNA expressions of key regulators of hepatic lipolysis were significantly up-regulation.The levels of ROS in plasma and liver were strikingly reduced with markedly increased liver T-AOC level and GSH-Px activity.Meanwhile,plasma T3 level was significantly improved by the enhanced activity of liver DIO1,mRNA expressions of NIS and TGB also showed up-regulation.levels of endogenous H₂S and CSE activity in liver were significantly improved.Metabonomics results of mice plasma and urine proved the preceding results and indicated FCPs might have potential mechanism in regulating protein synthesis and intestinal flora.Conclusions:FCPs intervention could markedly decrease adipopexis and regulate lipid metabolism by improving endogenous H₂S level,liver redox status,regulating thyroid hormones metabolism and accelerating lipid catabolism in mice fed with HFD.