Effects Of Epoxyeicosatrienoic Acids On Lipid Metabolism In Obese Rats And Potential Mechanisms

Objective:Obesity is a major health problem in the world,and it is a key factor causing metabolic diseases such as type 2 diabetes,heart disease,and hyperlipidemia.Obesity induces insulin resistance,and insulin resistance further promotes the occurrence and development of obesity with causing the body's glucose and lipid metabolism to fall into a vicious cycle.Epoxyeicosatrienoic acids(EETs)are metabolites derived from arachidonic acid.Recent studies have found that EETs can not only improve insulin resistance and prevent diabetes.This study was to investigate the effects of EETs on lipid metabolism in obese rats,and the potential regulation mechanisms.Methods:Healthy SD rats were selected,a diet-induced obesity rat model were induced by high-fat diet.The body weight of the rats in the model group and the control group were compared every week,and the blood was collected from the tail vein of the rats to detect the serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C).Then,the rats in the model group were randomly divided into obese group,11,12-EET group and 14,15-EET group,and the body weight,TG,blood glucose and other indicators were recorded regularly.The serum lipid content,oral glucose tolerance,insulin resistance(IR),inflammatory factors,adiponectin(ADPN),heme oxygenase(HO-1),and the mRNA expression levels of peroxisome proliferator activated receptor-?(PPAR-?),peroxisome proliferator activated receptor-?coactivator-?(PGC-1?),uncoupling protein 1(UCP1)and vascular endothelial growth factor(VEGF)were measured by ELISA and qRT-PCR to elucidate the regulatory effects of EETs on lipid metabolism and browning of white adipose.Results:(1)At the 15th week of high fat diet,the body weight of the model group increased by 26%compared with the control group,and compared with the control group,the serum TG,TC,LDL-C levels of the model group were significantly increased,while the HDL-C level was significantly reduced(P<0.05).(2)After 10 days of EETs intervention,compared with the obese group,the weight of rats in the EETs intervention group showed a downward trend and the serum TG level decreased significantly(P<0.05).(3)Compared with the control group,the insulin resistance index(HOMA-IR)of the obese group was significantly higher;Compared with the obese group,HOMA-IR of the two EETs groups decreased with the extremely significant difference of 14.15-EET group(P<0.01).(4)Compared with obese group,the levels of ADPN and HO-1 in serum of rats in EETs intervention group were significantly higher(P<0.05),while the levels of FFA,TNF-? and IL-10 in serum were significantly lower(P<0.05).(5)Compared with the obese group,the expression of PPAR-y in fat tissue of rats in the EETs intervention group was significantly decreased,while the expression of PGC-1 ? was significantly increased(P<0.05),in which 11,12-EET was more significant.(6)EETs can also promote the expression of UCP1(P<0.05),and promote the formation of capillaries and the browning of white adipose by increasing the expression of VEGF(P<0.05).Conclusion:(1)EETs can effectively reduce the body weight,TG and FFA content in serum and improve the IR level of obese rats,especially the effect of 14,15-EETs was more significant.(2)EETs can increase the antioxidant capacity and anti-inflammatory process of the body by increasing the levels of HO-1,ADPN and reducing the levels of TNF-? and IL-10 in obese rats,so as to reduce their lipid metabolism burden.(3)EETs can promote the browning process of white adipose in obese rats,and may promote the browning of white adipose by increasing the expression of UCP1,a heat producing factor,and regulating the expression of PPAR-y and PGC-1?.(4)EETs can promote the formation of blood vessels in adipose tissue and further promote the browning of white adipose by increasing the expression of VEGF.In conclusion,EETs can improve insulin resistance,antioxidant capacity,anti-inflammatory process,glucose and lipid metabolism,promote the browning process of white adipose,enhance heat production capacity and energy consumption level of obese rats,so as to inhibit the obesity induced by high-fat diet.Therefore,EETs have a positive and effective effect on lipid metabolism,which will be of great value to the prevention and treatment of obesity and diabetes.This study will provide a new idea and theoretical basis for the prevention and treatment of diabetes and metabolic syndrome.