Omentin‐1 attenuates adipose tissue inflammation via restoration of TXNIP/NLRP3 signaling in high‐fat diet‐induced obese mice

Abstract Omentin‐1 is an adipokine expressed by the adipose tissue and is reduced in obesity. This study was designed to calculate the protective efficiency and mechanism of omentin‐1 against inflammation of the adipose tissue in obese mice. A transgenic mouse model with omentin‐1 protein overexpression was established by crossing omentin‐1 transgenic mice with Fabp4‐Cre mice. Obesity was induced in the mice by feeding them a high‐fat diet for 10 weeks. Fabp4‐Cre‐mediated overexpression of omentin‐1 significantly increased serum omentin‐1 level, serum anti‐inflammatory factor levels, and expression of M2‐specific mRNAs; inhibited body weight and adipose tissue weight gain; improved glucose tolerance, insulin tolerance, and insulin sensitivity; decreased serum levels of insulin and proinflammatory factors, adipocyte size, and expression of M1‐specific mRNAs; suppressed macrophage infiltration; downregulated expression of proinflammatory factors; upregulated expression of anti‐inflammatory factors; and inhibited thioredoxin‐interacting protein (TXNIP)/NOD‐like receptor 3 (NLRP3) signaling in the adipose tissue of obese mice. An NLRP3 inhibitor (20 mg/kg MCC950) exhibited the same effects as overexpression of omentin‐1. Pretreatment with omentin‐1 inhibited lipopolysaccharide‐induced inflammation via TXNIP/NLRP3 signaling in RAW 264.7 macrophages. These findings suggest that omentin‐1 suppresses adipose tissue inflammation in obese mice, at least partly, via inhibiting the TXNIP/NLRP3 signaling pathway.