Adipose Tissue Nlrp3Inflammatory Pathway Is Critical To The Formation Of Insulin Resistance In Catch-up Growth

Purpose: Through the continuous dynamic observation of the general situation and contentof perirenal fat tissue in rats during growth process before and after recovering to normaldiet, evaluation of system insulin sensitivity, detection of Nlrp3inflammasome expressionin perirenal fat tissue and their downstream products the content of inflammatory cytokines;accordingly, preliminary discussion on the role of Nlrp3inflammatory in catch-up growth,then reveal the forming mechanism of insulin resistance in catch-up growth rats.Methods:According to the weight block，6-weeks-male SD rats were randomly dividedinto10groups after adaptive feeding for a week, including5groups (RN groups: from foodRestrict to Normal):for calorie restriction group and catch-up growth for1、2、4、8weeksgroup, while another5groups were age matched normal diet control groups (NC group:Normal Control). The Catch-up Growth model is established by calorie restriction for4weeks then returned to normal diet. Record of the daily food intake and body weight ofrats everyday were kept, at the end of the experiment, fasting blood glucose (FBG), serumtriglyceride (TG), free fatty acid (FFA), and total cholesterol (TC) were measured. Theviscera fat percentage was calculated by both weighing method and dual-energy X-ray(DEXA) detection. System insulin sensitivity was detected by fasting insulin (FINS) andhyper-insulinemic euglycemic clamp technique. Expressions of Nlrp3and Caspase-1inperirenal fat tissue were respectively valued by Real Time PCR and Western Blot detection.Serum IL-1β and IL-18levels were test by ELISA.Results:(1) After diet restriction for4weeks, the weight of RN groups was lower than normal NCgroups (P<0.05). After recovering of normal diet, NC groups increased rapidly, theirgrowth speed was faster than the NC groups, with visceral fat catch-up as outstandingcharacteristics. Perirenal fat ratio significantly reduced (P<0.05) in RN group afterrestriction for4weeks. Rapid increase in weight was noticed during1st and2nd week afterrecovering of normal diet. The rate of increase in weight gradually slowed down after2 weeks of recovering of normal diet, but Perirenal fat ratio was always higher than NCgroups (P<0.05).(2) After diet restriction, no obvious difference was found in fasting blood glucose andblood triglycerides between the two groups. After recovering of normal diet, RN groupshad a little rise in different degree, but the difference was not significant when comparedwith NC groups (P>0.05). After recovering of normal diet for1week, a transient rapidincrease in the blood triglyceride was noted which later decreased, but blood triglyceridelevel in RN groups was always higher than in NC groups (P<0.05).(3) Rats hyperinsulinemic euglycemic clamp technique showed the glucose infusion rate(GIR) mildly increased after4weeks of diet restriction, but did not have significantdifference in two groups. After recovering of normal diet, the GIR started to decreasegradually. During the4th week, GIR of RN group was lesser than that of NC group(P<0.05). RN groups got impaired system insulin sensitivity.8weeks after recovering ofnormal diet, GIR in RN groups was further reduced, significant increase in system insulinresistance was seen.(4) After restriction, the mRNA expression of Nlrp3and Caspase-1in Perirenal fat tissuewas significantly lower in RN groups (P<0.05), after recovering of normal diet it graduallyincreased. It reached the normal levels in2weeks, surpassed NC groups (P<0.05) duringthe4th week. The highest level was obtained in the8th week, significantly higher than thatof NC groups (P<0.01); the results of Western Blot showed the protein levels of Nlrp3andCaspase-1were similar with mRNA expression levels. Serum inflammatory factor such asIL-1β and IL-18decreased significantly after4weeks of diet restriction (P<0.05), theyalso reached a peak during8th week of recovering of normal diet, their tendency of changein level was consistent with Nlrp3inflammasome.Conclusion: The increased expression of Nlrp3inflammasome accompany with insulinresistance in rats, Nlrp3inflammatory pathways in viscera adipose tissue may be pursued asan important mechanism of the formation of insulin resistance in Catch-up Growth.