The Effect Of Vitamin D₃ On Adipose Inflammation In Type 2 Diabetic Rats Through NF-?B/PPAR? Pathway

ObjectiveTo observe the effect of 1,25-dihydroxyvitamin D3?1,25?OH?₂D₃?intervention on the general condition,glucolipid metabolism,the plasma levels of fasting serum lisulin?FINS?and inflammatory factors,as well as the protein expressions of nuclear factor kappa-B?NF-?B?,Peroxisome Proliferator-activated receptor??PPAR??and interleukin-1??IL-1??of type 2 diabetic?T2DM?rats,we established type 2 diabetic rat models with high-fat/carbohydrate diet and intraperitoneal injection of streptozotocin?STZ?.This study was designed to discuss the mechansm and effects of vitamin D₃?VD₃?on insulin resistance and micro inflammation state of T2DM rat pancreas and adipose tissue.Materials and methodsSelected 15 rats randomly from 120 SD rats?4-week age?into the normal control group and fed with ordinary diet,while the rests were fed with high-fat and high-sugar diet for 5 weeks and then treated with intraperitoneal injection of STZ?35mg/kg?to form a T2DM rat model.Rats with fasting blood glucose?FBG??11.1mmol/L for 3 times concomitant with a week-long polydipsia,polyphagia,polyuria were classified as T2DM model rats and subsequently divided into T2DM group?n=20?,high-dose VD group?n=20?,middle-dose VD group?n=20?and low-dose VD group?n=20?at random,respectively.The high-,middle-,low-dose VD intervention groups rats were administered with 0.075?g/kg,0.15?g/kg,0.3?g/kg VD₃ mixture by gavage everyday,while the normal rats were treated with peanut oil correspondingly.Blood samples were collected at-1 and 0 week before,as well as 4and 12 weeks after the intervention,the levels of serum FBG,total cholesterol?TC?,Triglyceride?TG?,high density lipoprotein-cholesterol?HDL-C?,low-density lipoprotein-cholesterol?LDL-C?were tested using automatic biochemical analyzer.Serum fasting insulin?FINS?and plasma TNF-?,IL-6,IL-1?,chemerin levels were measured through ELISA kit.After 4 and 12 weeks of intervention,rats were executed in batches,and visceral adipose tissue and pancreatic tissue were collected for histomorphology observation.Protein expressions of NF-?B,PPAR?and IL-1?in adipose tissue were detected.SPSS 25.0 was used for statistical analysis,and the test level was?=0.05.Results?1?General condition:The T2DM rat model was successfully established by igh-fat/carbohydrate diet combined with intraperitoneal injection of STZ.The ental condition of model rats were worse than those in the normal control roup,and the model group rats gained weight slowly.?2?Glycometabolism and lipid metabolism condition:The FBG of model rats was ignificantly higher than normal rats?P<0.05?.After 4-week intervention,the BG of VD₃ intervention groups was controlled distinctly and the FBG of VD₃ ntervention groups were significantly lower than those of the T2DM group after 2-week intervention?P<0.05?.The serum levels of TC,TG,LDL-C of model ats were much higher than those of the normal control group,while the HDL-C evel was lower.At the end of the study,the TC,TG,LDL-C levels of VD ntervention groups,particularly the high-dose VD group,were significantly ecreased while the HDL-C level was increased.?3?Serum FINS level:The serum FINS levels of model rats were higher than those f normal rats?P>0.05?;after 4 weeks of intervention,serum FINS levels of igh-and middle-dose VD intervention group were higher than that of the 2DM group.In the following course of intervention,FINS levels in VD ntervention groups returned to the normal levels and the serum level of FINS in he T2DM group was much lower than those of other groups?P<0.05?.?4?Conditions on plasma inflammatory factors:After 4-week intervention,plasma evels of TNF-?,IL-6 and chemerin in the T2DM group were significantly igher than normal group?P<0.05?,as high-and middle-dose VD intervention ecreased the levels of plasma TNF-?,IL-6 and chemerin apparently?5?The levels of inflammatory factors in VD groups were significantly lower than hose in the T2DM group at the end of week 12 and the difference was tatistically significant?P<0.05?.?6?Pathological morphology of adipose tissue and pancreatic tissue:Compared to the normal control group,adipose cellularity of the T2DM group was incomplete and infiltrated with inflammatory cells.After the intervention of VD,the adipose ellularity of high-and middle-dose VD group were evidently improved.Compared with the normal group,the pancreatic tissue of rats in the T2DM roup was seriously damaged,shown in fuzzy boundary,disorganized islet cells nd inflammatory cell infiltrates.The islet condition of rats in VD intervention roups were better than the T2DM group.The effect was more obvious in high- and middle-dose VD groups.?7?The protein and mRNA expressions of adipose tissue NF-?B?P65?,PPAR?,IL-1?in rats:The protein and mRNA expressions of p65 and IL-1?protein expression in the T2DM group were higher than those in other groups;moreover,the anti-inflammatory effect of middle-dose VD group was more obvious.The expression of PPAR?in T2DM group was lower than those in other groups.In all VD intervention groups,middle-dose group had the most significant effect?P <0.05?.Conclusions?1?Compared with the normal rats,severe glucose and lipid metabolism disorders and insulin resistance were existed in T2DM rats,as the levels of FBG,blood lipids and inflammatory cytokines elevated obviously.The expressions of P65 mRNA and P65,IL-1?protein were increased in T2DM rats adipose tissue accompanied by evident inflammatory response.?2?1,25?OH?₂D₃ intervention could lead to a decrease in the levels of FBG,blood lipids and plasma inflammatory factors,thereby improve the inflammatory state of T2DM rats.?3?1,25?OH?₂D₃ intervention could improve the tissue morphology of adipose and pancreatic.VD₃ intervention may reduce the expression of NF-?B and IL-1? through the activation of PPAR?,and thus inhibit insulin resistance.