Regulatory Mechanism Of Chlorogenic Acid On Hepatic Lipid Metabolism In Rats

Aim of the study:To explore the molecular mechanism of chlorogenic acid on hepatic lipid metabolism disorders induced by high fat diet.Background:Obesity is becoming a major common health question in the world, due to the lifestyle and life quality have changed deeply. It is well know, liver plays a major part in maintaining energy balance and lipid metabolism homeostasis. However, hepatic lipid metabolism will be disturbed in the case of excessive fat intake, further more, it could even develop non-alcoholic steatohepatitis. With the high prevalence of obesity, a serise of chronic disease induced by obestiry threat human healthy. Hence, it is necessary to promote healthy life style and improve food stucture in the community to minimize and if possible to prevent the incidence of obesity.chlorogenic acid which is widely distributed in plants and rich in the fruits and vegetables, was reported to possess antioxidant, antiviral and lipid-lowering effect. However, the molecular mechanism of chlorogenic acid on hepatic lipid metabolism was not well understood.Methods:Following acclimatisation, male Sprague Dawley rats (130±10g) were randomly assigned into five groups. The control group (NC group) was fed normal diet and administered daily ultrapure water. The high-fat model group (HFD group) receivied high-fat diet and was given ultrapure water by stomach perfusion daily. The low-dose chlorogenic acid treatment group (HFD-LC group) was maintained on the high-fat diet and pretreated with chlorogenic acid (20mg·kg-1·d-1) by intragastric administration every day. The high-dose chlorogenic acid treatment group (HFD-HC group) was fed high-fat diet and administered chlorogenic acid (90mg·kg-1·d-1) by gavage daily. The rosiglitazone group (HFD-ROS group) was allowed high-fat diet and administered rosiglitazone (3mg·kg-1·d-1) every day. After12weeks, male Sprague Dawley rats were anesthetized and sacrificed, the serum contents of TC, TG, LDL-c, HDL-c, FFA, ALT and leptin, as well as hepatic TG were measured. LXRa, SREBP-1c, ACCa, FAS, AP2, FAT/CD36, LPL, HMGCR, PPARa, CPT-1and CPT-2mRNA expression were studied using real-time PCR. Hepatic tissue sections were stained with hematoxylin and eosin to detect the pathological changes.Results:Chlorogenic acid could not only significantly reduce weight and weight gain induced by high fat diet, but also improve serum lipid profile. Leptin resistance was reversed after12weeks pretreatment with chlorogenic acid. Chlorogenic acid could effectively decrease hepatic tissue weight in accordance with reduction of triglyceride. Real-time PCR results showed that chlorogenic acid could improve hepatic lipid metabolism disorders in three aspects. Firstly, the expression of hepatic LXRα、SREBP-lc mRNA involved in hepatic lipogenesis (FAS, ACCa) was down-regulated. Secondly, genes that control hepatic fatty acid β-oxidation (PPAR, CPT-1and CPT-1) were up-regulated by chlorogenic acid. The expression of mRNA of AP2and FAT/CD36which plays a major part in hepatic fatty uptake was reduced with chlorogenic acid. Biopsy results showed that a large number of hepatic vacuoles and excessive accumulation of lipid droplets were induced by high-fat diet, chlorogenic acid could reduce fat cavitation and inhibit fat accumulation.Conclusion:chlorogenic acid has the potential to ameliorate disorders of lipid metabolism through altering mRNA expression of PPARa, SREBP-lc and LXRa, which are involved in multiple intracellular signaling pathways.