Omentin-1 attenuates adipose tissue inflammation via restoration of TXNIP/NLRP3 signaling in high-fat diet-induced obese mice |
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Authors: | Hongli Zhou Zuo Zhang Guisheng Qian Jiyin Zhou |
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Affiliation: | 1. National Drug Clinical Trial Institution, The Second Affiliated Hospital, Army Medical University, Chongqing, 400037 China Equal contributors;2. Institute of Respiratory Diseases, The Second Affiliated Hospital, Army Medical University, Chongqing, 400037 China;3. National Drug Clinical Trial Institution, The Second Affiliated Hospital, Army Medical University, Chongqing, 400037 China |
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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. |
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Keywords: | adipose tissue inflammation obese mice Omentin-1 overexpression TXNIP/NLRP3 signaling pathway |
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