MiR-1934, Downregulated In Obesity, Protects Against Low-grade Inflammation In Adipocytes

PARTⅠTHE EXPRESSION OF MIR-1934 IN MICE AND HUMAN OBESITYObjective: Chronic low-grade inflammation in adipose tissue has been known as the core feature in obesity-related metabolic disorders. In recent years, several micro RNAs have been reported to be dysregulated in obesity and associated with adipose tissue inflammation. Herein we investigated the expression of mi R-1934 in both mice and human obesity.Method: Male C57BL/6J mice were randomly assigned to receive a chow diet(CD) or a high-fat diet(HFD) for 8 weeks. Omental adipose tissue was obtained from 21 lean and 14 obese subjects undergoing laparoscopic cholecystectomy. Serum was obtained from another cohort with 25 lean subjects and 24 obese subjects. Inflammatory cytokines and mi R-1934 expressions in both mice and human subjects were determined by RT-q PCR, and the relationship of serum mi R-1934 and clinical parameters were analyzed.Results: Compared with chow-diet fed mice, obese mice exhibited higher inflammatory cytokine expressions and lower mi R-1934 expression in epididymal AT, accompanied by dysregulated blood glucose, TG and insulin levels. Similarly, mi R-1934 expression was down-regulated as well in omental AT of obese subjects in comparison with lean subjects with increased inflammatory factors. Compared to the lean subjects, the obese subjects were associated with a worse metabolic profile(elevated levels of BP, FPG, 2h PG, Hb A1 c, FINS, TG, and reduced levels of HDL), as well as a higher pro-inflammatory state(elevated levels of hs-CRP and reduced levels of Ap N).The circulating mi R-1934 was also lower in obese subjects and its levels were negatively correlated with BMI, WC, FINS, HOMA-IR, LDL-c and hs-CRP, and positively associated with HOMA-IS.Conclusion: mi R-1934 was down-regulated in both mice and human obesity, suggesting a possible role of mi R-1934 in adipose tissue inflammation. Serum mi R-1934 was also down-regulated in obese subjects and significantly correlated with clinical parameters, which may provide us with a novel biomarker for obesity-related metabolic disorders.PART ⅡMIR-1934 PROTECTS AGAINST LOW-GRADE INFLAMMATION IN ADIPOCYTESObjective: Recently, dysregulated micro RNAs in obesity have been reported to be involved in adipose tissue inflammation. It has been previously demonstrated that mi R-1934 was specially regulated by adiponectin, an anti-inflammatory adipokine, in adipose tissue. Herein we investigated the role of mi R-1934 in the regulation of inflammatory response.Method: In vitro, mi R-1934-5p mimic or negative control was delivered into 3T3-L1 preadipocytes or mature adipocytes and then challenged with or without 50 ng/ml TNF-α for an additional 24 h. In vivo, 3T3-L1 preadipocytes were transfected with a lentivirus containing the mi R-1934 sequence or a screambled control sequence, then 3T3-L1 preadipocytes were injected sc in the back of BALB/c nude mice. RT-q PCR was performed to evaluate the expression of mi R-1934 and inflammatory cytokines.Results: The down-regulation of mi R-1934 in obesity was mimicked by TNF-α treatment of 3T3-L1 adipocytes. Moreover, overexpression of mi R-1934 suppressed the TNF-α-induced gene and protein expression of interleukin-6(IL-6) and monocyte chemotactic protein-1(MCP-1) in 3T3-L1 adipocytes. De novo formed AT in nude mice transplanted with 3T3-L1 preadipocytes overexpressing mi R-1934 displayed a reduction in IL-6, TNF-α, IL-1β and an enhancement in IL-10 gene expression when compared with transplant with 3T3-L1 preadipocytes overexpressing mi R-1934 scrambled control sequence.Conclusion: The anti-inflammatory effect of mi R-1934 was confirmed by both in vivo and in vitro experiments, which may represent a novel mechanism for controlling AT inflammation.