Study On Duodenal-jejunal Bypass Reducing Inflammation Of Visceral Adipose Tissue In GK Rat

BackgroundType 2 diabetes(T2D)is a kind of chronic disease that seriously endangers public health.Since Friedman first proved that subtotal gastrectomy affects the control of blood glucose,bariatric surgery has become the preferred treatment for obese patients with T2D.However,the mechanisms by which bariatric surgery improves glucose metabolism are not completely understood.Duodenal-jejunal bypass(DJB)is a commonly used experimental model designed by Rubino for the exploration of weight loss-independent anti-diabetic effects of bariatric surgery.It is an effective intervention method for T2D in both rodent model and human.In recent years,a large number of studies have shown that inflammation is one of the important factors leading to ins?lin resistance.Inflammatory factors can affect ins?lin sensitivity throug the action of of blood and/or paracrine.As an endocrine organ,visceral adipose tissue secretes inflammatory cytokines,such as interleukin-6(IL-6),tumor necrosis factor-?(TNF-?),interleukin-1?(IL-1?)and induces macrophage infiltration,which is an important risk factor of ins?lin resistance.MethodsTen Goto-Kakizaki(GK)rats were randomly divided into DJB group and sham group.The body weight,body length,food intake,body length ratio,FBG,IPGTT,FINS and HOMA-IR were measured before and 1-8 weeks after operation.The rats in the two groups were killed at the 8th week.RT-PCR was used to detect the expression of IL-6,TNF-? and IL-1? in omental adipose tissue(OAT)and mesenteric adipose tissue(MAT)at RNA level.The expressions of IL-6,TNF-?,IL-1? and macrophages in OAT and MAT of the two groups were determined by western blotting,immunohistochemistry,and immunofluorescence,respectively.Results1.The overall survival rate in the two groups was 100%in 8 weeks2.There was no significant difference in body weight,food intake,body length and weight/length between the DJB group and the sham group.3.Compared with sham group,the mRNA levels of IL-1? in OAT and MAT in DJB group were significantly lower(P<0.05).There was no significant difference in the mRNA levels of IL-6 and TNF-?.4.The expression of IL-6 and IL-1? in OAT of DJB group was significantly lower than that of sham group(P<0.05),and the expression of TNF-? was lower but no significant difference.The expression of IL-6 and IL-1? in MAT in DJB group was significantly lower than that in sham group(P<0.05).The expression of IL-6 in OAT of DJB group was significantly lower than that of MAT(P<0.01).5.The level of IL-1? in OAT was significantly correlated with FINS and HOMA-IR(P<0.01),the level of IL-6 was significantly correlated with FBG(P<0.01).The level of IL-6 in MAT was significantly correlated with FBG(P<0.05).6.The number of CD68 positive cells in OAT and MAT in DJB group was significantly lower than that in sham operation group(P<0.05).7.The number of CD68-positive IL-6-expressing cells and CD68-positive IL-1?-expressing cells in OAT and MAT in DJB group was significantly lower than that in sham group(P<0.05).ConclusionThe DJB procedure improved the glucose metabolism of GK rats without inducing weight loss.The change in the inflammatory state of visceral adipose tissue after DJB may play a role in the amelioration of ins?lin resistance.