Effects Of Green Tea Polyphenols On The Expression Of HMGCS2in Rats Fed With High Fat Diet

Objection: Ketone bodies (KB) are produced by the incomplete oxidation of fattyacid, including β-hydroxybutyric acid, acetoacetate and acetone. KB are traditionallyalternate fuels which are produced in liver and used by extrahepatic tissues, and arethe reason for diabetic ketoacidosis (DKA). Furthermore, the production of KB isincreased under conditions of fasting, prolonged exercise, caloric restriction, andintake of high-fat and low-carbohydrate diets. Recent Studies have indicated aprotective anti-oxidant and energy replenishing roles for KB in experimental modelsof Alzheimer’s disease, Parkinsonism, epilepsy and stroke, with the exact mechanismof anti-oxidative role of KB not being revealed.3-Hydroxy-3-methyl-glutaryl-coenzyme A synthase (HMGCS2), which was reportedexisting in human and mammalian liver, is now found to be widely expressed inkidney, brain and other tissues. Its expression and activity is positively correlated withthe amount of KB. Proteomics analysis shows that the kidney HMGCS2has differentprotein expressions between SHR and SHRSP, and the PPARα agonist clofibratesignificantly improves the protein expression of HMGCS2, increasing the survivalrate of SHRSP by enhancing the antioxidant capacity of the kidney. MetabolicSyndrome (MS) is a combination of medical disorders, mainly including excessabdominal fat, insulin resistance, hypertension, dislipidemia, hyperglycemia. It isrecognized that insulin resistance is the common pathogenic mechanism. MS is thefocus of attention at home and abroad nowadays, being the most important risk factorfor cardiovascular disease, while the latter is currently the global No.1cause of death. Numerous studies show that oxidative stress plays an important role in MS and thetreatment of anti-oxidation can improve the illness state. Kidney is one of the majortarget organs in MS, although constituting only0.5%of the body mass, consume10%of the total body oxygen consumption along with large ROS production. We hereinvestigated the effects of green tea polyphenols on the expression of HMGCS2inrats fed with high fat diet and its regulation pathway.Method:(1) Male weaned Wistar rats were housed in cages under controlledconditions (22℃-26℃;40%-50%humid; a12-h light/dark cycle). Animals wererandomly divided into five groups: normal control group (CON); high fat group(HFG); low, moderate, high dose GTPs groups (0.8g/L,1.6g/L,3.2g/L, G1, G2, G3);6in each group. The CON group fed a normal diet, the HFG group fed a high fatdiet while the GTPs groups fed the same high fat diet with drinking water containingGTPs. GTPs intervention were applied when the body weight of the rats were up to180g.(2) After26weeks, serum concentrations of fasted glucose, total cholesterol,triglyceride, LDL and HDL were measured by ELX800using their correspondingcommercial kits. The expressions of HMGCS2and SIRT3were determined byreal-time PCR and western blot.Result:(1) The body weight and fat coefficient, serum levels of TC, TG,LDL-C/HDL-C, FPG content in HFG group were significantly higher than those inCON group (P＜0.05); compared with HFG group, the body weight and fatcoefficient, serum TC, TG, LDL-C/HDL-C and FPG levels in GTPs groups weresignificantly decreased (P＜0.05).(2) The expression of renal HMGCS2proteinwas decreased in HFG group, whereas GTPs increased the expression of HMGCS2(P＜0.05), but no significant difference were found among the three GTPs treatedgroups. Besides, the expression of SIRT3had no significance among the five groups.(3) The expressions of hepatic HMGCS2mRNA and protein were increased in HFGgroup, whereas GTPs decreased the expressions of HMGCS2mRNA and protein (P＜0.05), but no significant difference were found among the three GTPs treatedgroups. Conclusion:(1) GTPs dissolved in the drinking water can improve the high fatinduced obesity, hyperglycemia and hyperlipidemia.(2) High fat diet decreased therenal HMGCS2protein expression while GTPs increased the renal HMGCS2proteinexpression, but not through the SIRT3pathway.(3) High fat diet increased the hepaticHMGCS2mRNA and protein expressions while GTPs decreased the hepaticHMGCS2mRNA and protein expressions. The exact mechanism remains to beexplored.