Phosphorylation Of STAT3 Was Involved In Lipid Metabolism Disorders And Intervention Of Phytoestrogen In Ovariectomized Rats

Due to the lack of estrogen,a series of hormone-related diseases will be produced in menopause,For example,the diseases of obesity,coronary heart disease,osteoporosis,and menopausal syndrome seriously threaten women's health.The increase and redistribution of body fat in postmenopausal women is easy to form visceral obesity,and the control of postmenopausal obesity is the premise and basis for reducing a series of postmenopausal related diseases.Hormone replacement therapy can reduce these symptoms but increase the risk of breast cancer,stroke,and cardiovascular embolism.The phytoestrogen has similar structure and function to estrogen and can replace estrogen to reduce the risk of the above diseases.The study found that weight gain in ovariectomed rats is related to increased food intake,but after eliminating the effects of food intake,lipid metabolism in the liver also directly plays an important role.In vitro studies have found that estrogen deficiency can promote the expression of adipogenic genes to promote hepatic triglyceride synthesis.Studies have shown that STAT3 is involved in the regulation of hepatic lipid metabolism in the high-fat model,but it is still unclear whether STAT3 regulates the adipogenic gene in the ovariectomized model.Whether the phytoestrogens regulate the expression of the adipogenic genes through STAT3 in the ovariectomized rat model and thus reduce the weight of ovariectomized rats,it has not been reported.Objective: in the present study,we used Sprague-Dawley(SD)rats and L02 cells to explore the mechanism whereby phytoestrogen exerted repressive effects on weight gain in ovariectomized rats and the role of STAT3 protein in it.As a result,our data may provide more evidence for postmenopausal weight gain dietary intervention in the future.Methods: animal grouping and gavage experiments;HE staining and triglyceride kits were used to detect liver tissue triglyceride content,real-time quantitative PCR was used to detect adipogenic gene m RNA expression;Western blotting was used to detect gene protein levels,using cell transient The staining experiment knocked out STAT3.Results:? Phosphorylation of STAT3 was involved in lipid metabolism disorders and Intervention of phytoestrogen in ovariectomized rats.1.Effect of phytoestrogen on basic indexes of ovariectomized rats: SD rats were randomly divided into 7 groups: Sham operated(SHAM),ovariectomy(OVX),ovariectomy + estrogen(OVX+E2),ovariectomized + equol(OVX + EQ),ovariectomized + isoliquiritigenin(OVX + ISL),ovariectomized + glabridin(OVX + GLA)and ovariectomized + genistein(OVX+GEN),10 in each group.In the ovariectomized group,the bilateral ovaries were removed surgically,and the sham operation group only removed the same amount of adipose tissue.Keep for 50 days.The results indicated that ovariectomy could significantly increase body weight and reduce uterine weight,increase food intake,and increase blood glucose level.Phytoestrogens could reverse these results.2.Effect of phytoestrogen on hepatic lipid metabolism: the results showed that phytoestrogen can improve liver fat content to varying degrees.The phytoestrogen group could reduce the expression of SREBP1,ACC1,FAS and SCD1 induced by ovariectomy,but had no inhibitory effect on the expression of C/EBP? and PPAR? genes.3.Effect of phytoestrogen on hepatic STAT3 protein expression: phytoestrogen can inhibit the phosphorylation of STAT3 induced by ovariectomy in liver.4.Effects of estrogen supplementation/removal on weight and lipid metabolism in ovariectomized rats: after 50 days of the experiment,4 rats in SHAM,OVX,and OVX+E2 groups were remained.The dosing regimen was changed at 55 days.The SHAM group remained unchanged.The rats in the OVX group were supplemented with E2.Rats in the OVX+E2 group were not given E2 and continued to be raised for 100 days.The results showed that in the OVX group,compared with the original OVX group,the weight loss,uterine weight increase,hepatic STAT3 protein expression,adipogenic gene SREBP1 expression,and triglyceride content decreased in the OVX group after the estrogen supplementation;In the +E2 group,the reversal of estrogen withdrawal was observed in the OVX+E2 group compared with the original OVX+E2 group.5.Effects of phytoestrogens on lipid metabolism in vitro: in vitro we used a high-glucose L02 cell model to simulate the in vivo environment.The results show that phytoestrogen can inhibit the increase of high glucose-induced triglyceride levels by STAT3/SREBP1.? Phosphorylation of STAT3 was involved in lipid metabolism disorders and Intervention of estradiol in energy-control-ovariectomized rats.1.The effect of ovariectomy on the basal index of the rats in energy control model: SD rats were random Ly divided into four groups: energy-controlled SHAMc and OVXc groups,and energy-uncontrolled SHAMu and OVXu groups.Rats with energy control were given an equal amount of food each day at the same with SHAMc group;rats without energy control were fed freely for 8 weeks.The results showed that under the control of energy,ovariectomy can increase the weight of rats,reduce the weight of the uterus,and increase food utilization.2.The effect of ovariectomy on lipid metabolism of the rats in energy control model: with equal energy input,ovariectomized rats increased liver triglyceride levels,the adipogenic expression,and phosphorylation of STAT3.3.Effect of estrogen deprivation on lipid metabolism in L02 cells: in the energy-controlled ovariectomized rat model,we used an estrogen deprivation L02 cell model to simulate in vivo experiments.The results showed that compared with the control group,E2 group significantly reduced the phosphorylation of STAT3 and adipogenic genes SREBP1 and FAS.This shows that in vitro models,estrogen can directly inhibit the STAT3/SREBP1 pathway to inhibit the increase of triglyceride content.Conclusion: in the ovariectomized rat model,we found that,regardless of energy control,the lack of estrogen leads to an increase in body weight in rats,and the effect of estrogen in suppressing body weight in ovariectomized rats is reversible.In a non-energy controlled ovariectomized rat model,the body weight of ovariectomized rats was not only related to food intake but also related to liver lipid metabolism.Under energy control,the body weight of ovariectomized rats is related to estrogen-regulated hepatic lipid metabolism.Phosphorylated STAT3 plays an important role in liver lipid metabolism.Ovariectomy activates the phosphorylation of STAT3,promotes the expression of adipogenic genes,causes an increase in liver triglyceride levels,and ultimately leads to increased body weight in rats.Phytoestrogen can be used as a substitute for estrogen,inhibiting the phosphorylation of STAT3 caused by ovariectomy,inhibiting the expression of adipogenic genes and reducing liver triglyceride levels,thereby inhibiting the increase in body weight of rats caused by ovariectomy.