Role Of GLUT4and UCP2in Nonalcoholic Fatty Liver Disease And The Effect Of Berberine On Expressions Of GLUT4and UCP2

Objective: With the rapid development of economy, people’s diety structureand lifestyle have changed dramatically, resulting in the increase in prevalenceof nonalcoholic fatty liver disease (NAFLD). Studies find that insulin resistance,metabolic syndrome, oxidative stress, increased susceptibility to apoptosis andabnormal lipid metabolism are involved in the pathogenesis of NAFLD, butstill can’t fully explain its pathogenesis. Uncoupling protein2(UCP2) andglucose transporter4(GLUT4) are closely related to the carbohydrate and lipidmetabolism, oxidative stress, insulin resistance and energy metabolism. It is notsure that which role they act as in the pathogenesis of NAFLD. Meanwhile,there is no specific effective treatment medicine of NAFLD, and most of thedrug has some side effects in the treatment at the same time. It is also not surewhich kind of efficacy medicine there exists. Berberine (BBR) is regarded as asafe and inexpensive drug, which has hypoglycemic and lipid-lowering effect,and also can improve insulin resistance. Therefore we speculated that whether itcan be used for the treatment of NAFLD. Our study was aimed to investigatethe role of UCP2and GLUT4in the pathogenesis of NAFLD, and treatmentmechanism of berberine on NAFLD, which may provide a new theoretical basisfor the pathogenesis of NAFLD, and a new way to the clinical treatment ofNAFLD. Methods: The56male SD rats were randomly divided into two groups after one week of conventional breeding: normal group(n=24, fed withnormal diet), and model group(n=32, fed with high-fat diet). In fifth weekendand ninth weekend respectively,8rats were put to death in each group, then theremaining rats in model group were randomly divided into two groups: modelgroup(n=8) and intervention group(n=8). The intervention group was givenberberine hydrochloride by intragastric administration, and the normal groupand model group were given the same amount of distilled water. All rats werekilled after4weeks. After blood samples of each rat were collected from theinferior vena cava, the aspartate aminotransferase (AST), alanineaminotransferase(ALT), total cholesterol(TC), triglyceride(TG), fasting bloodglucose(FBG), fasting serum insulin(FINS) in serum were detected, and withhomeostasis model assessment of insulin resistance(HOMA-IR) index wascalculated. In addition, liver tissue was cut into paraffin sections. Thepathological change of the liver tissue was observed with HE staining by lightmicroscope, and the expressions of UCP2and GLUT4protein were detected byimmuneohistochemistry. Meanwhile, some of the liver tissue was stored in-70℃refrigerator after being frozen in liquid nitrogen, for detection of theexpression of GLUT4mRNA with the method of RT-PCR. Results:1. AST、ALT、TC、TG、FBG、FINS、HOMA-IR in serum of rats in model group werehigher than normal group, but AST、ALT showed no statistical differencebetween the two groups in the fifth weekend (P>0.05).2. With the high-fatdiet feeding time extending, AST, ALT, TC, TG, FBG, FINS, HOMA-IR in serum of rats in model group showed a trend of increase (P <0.05).3.In thesame period, AST, ALT, TC, TG, FBG, FINS, HOMA-IR in serum of rats in theintervention group were lower than model group (P <0.01), but still higher thannormal group (P <0.01).4. Compared with normal group, the expression ofGLUT4in liver tissue of rats in model group was decreased (P <0.01), and theexpression of UCP2was increased (P <0.01).5.With high-fat diet feeding timeextending, the expression of GLUT4in liver tissue in model group wasgradually decreased(P <0.01), but the expression of UCP2was increased (P<0.01).6. In the same period, the expression of GLUT4in liver tissue in theintervention group was more than normal group (P <0.01), and the expressionof UCP2was less than model group (P <0.01), but both of them were not returnto normal (P <0.01). Conclusion:1.A high-fat diet can successfully establishthe NAFLD model of rat after a certain period of time. The model displayedclearly hepatic steatosis, steatohepatitis, insulin resistance, hyperinsulinemia.etc.2.With the extension of the high-fat feeding time, the expressions ofGLUT4mRNA and protein were statistically decreased, and the expression ofUCP2protein was statistically increased. Rats exhibited obviously disorder oflipid metabolism, insulin resistance, and steatosis, inflammation, necrosis inliver tissue. It suggests GLUT4and UCP2may play an important role in thedevelopment of NAFLD, which may be associated with insulin resistance, lipidmetabolism, oxidative stress and energy metabolism. etc.3.Berberine had theeffect of hypoglycemic and regulation of lipid metabolism. It also can improve insulin resistance and reduce inflammation. Berberine reduced the degree ofliver pathological changes and improved liver function finally. In a word,berberine plays a important role in the treatment of NAFLD.4.Berberinesignificantly promoted the expressions of GLUT4mRNA and protein, andreduced the expression of UCP2protein in liver tissue, which may be one of themechanisms for the treatment of NAFLD.