The Formation And Biomarkers Of Metabolic Syndrome Mediated By Sweet Receptors

Objective To investigate the correlation between metabolic indices and the expression of sweet receptors,the model of early metabolic syndrome in rats was established via energy and non-energy sweeteners,then the effect on body weight,fat index,glucose tolerance,blood lipids,blood pressure and related hormones were determined.At the same time,serum risk factors were screened for warning of excessive intake of sweeteners.Method Male SD rats were randomly divided into 8 groups,control group(CON),free drinking fructose(Fru2.5%,Fru5%,and Fru10%),fructose via gavage(Fru4g/kg,Fru8g/kg),APM0.1%which was as the same sweetness as Fru5%and APM0.12g/kg,n=6 in each group.The oral glucose tolerance test and blood pressure were determined after breeding for 6 weeks.Rats were put to death after 60 days'feeding,and the heart,brain,adrenal gland,thoracic aorta,and white fat were separated and the viscera index was calculated.The skeletal muscle was separated and the content of Glucose(Glu),adenosine triphosphate(ATP)and nicotinamide adenine nucleotides(NAD~+)were detected.The expression of taste receptor type 1 member 3(TAS1R3)in small intestine was detected,and sensitive biomarkers were screened.Results After 60 days'intake of sweeteners,body weight was significantly increased in group Fru10%,while fructose in the gavage group had a trend of reducing body weight and fat synthesis.And APM had little effect on body weight.All sweeteners could cause heart hyperplasia and aortic thinning.The glucose tolerance of the rats was not impaired.On the contrary,insulin sensitivity was promoted after the administration of fructose and APM.And the content of Glu,ATP and NAD~+in skeletal muscle was increased by APM and fructose via gavage.That meant the transformation of muscle energy was promoted,which might be the reason for not increasing body weight.All sweeteners could reduce high-density lipoprotein(HDL-C).Fructose increased triglyceride(TG)more easily while APM did not affect TG levels.Rats'blood pressure was not significantly increased while adrenaline(Adr)and corticosterone(CORT)were obviously elevated after drinking fructose and gavage of APM.Moreover,the concentration of glucagon-like peptide-1(GLP-1)was risen significantly,which was a precursor of insulin resistance(IR).The level of insulin-like growth factor-1(IGF-1)was decreased after the intake of any sweeteners.And as the sweetness increased,the expression of TAS1R3 was increased first and then decreased.The content of homocysteine(Hcy)increased obviously,and its change was earlier than impaired glucose tolerance,IR and hypertension.Conclusion APM had a weaker effect on metabolism than fructose and was related to the expression of TAS1R3.Long-term intake of sweeteners might have hidden dangers to interfere with lipid metabolism and glucose tolerance.The increase of Hcy content was earlier than IR and hypertension,which meant Hcy could be an ideal biomarker for metabolic disorders caused by sweeteners.