High n-3 fatty acids counteract hyperglycemia-induced insulin resistance in fat-1 mice via pre-adipocyte NLRP3 inflammasome inhibition. Issue 1 (9th December 2020)

• Record Type: Journal Article
• Authors: Yu, Qingyao; Wang, Tiantian; Wang, Feng; Yang, Yong; He, Canxia; Yang, Wenge; Zhang, JinJie; Zou, Zuquan
• Is Part Of: Food & function. Volume 12:Issue 1(2021)
• Page Start: 230
• Page End: 240
• Publication Date: 2020-12-09
• Subjects: Food -- Analysis -- Periodicals; Food -- Composition -- Periodicals; Nutrition -- Periodicals; 664.07
• DOI: 10.1039/d0fo02092c
• Languages: English
• ISSNs: 2042-6496

Abstract

Abstract : Hyperglycemia induces TXNIP expression and triggers NLRP3 inflammasome-dependent IL-1β secretion, which is counteracted by n-3 PUFAs such as DHA through the PI3K/Akt pathway-mediated downregulation of TXNIP in adipose pre-adipocytes. Abstract : Although n-3 polyunsaturated fatty acids (n-3 PUFAs) have potential anti-insulin resistance activity, the mechanism remains largely unknown. In this study, increased glucose resistance, insulin sensitivity, and lower glycemia were observed upon streptozotocin (STZ) treatment in n-3 PUFA-enriched fat-1 mice compared to wild type (WT) mice. Endogenous n-3 PUFAs in fat-1 mice were found to impair hyperglycemia or high glucose level-induced nucleotide-binding domain and leucine-rich repeat pyrin 3 domain (NLRP3) inflammasome activation and inhibit IL-1β secretion in adipose tissues. In addition, endogenous n-3 PUFAs also inhibited high glucose-induced caspase-1 activity and IL-1β secretion in pre-adipocyte-enriched stromal vascular fractions (SVF) isolated from adipose tissues. Furthermore, in 3T3-L1 pre-adipocytes, high levels of glucose induced thioredoxin interacting protein (TXNIP) expression and activated the NLRP3 inflammasome, which was counteracted by docosahexaenoic acid (DHA), the major n-3 PUFA in fat-1 mice, by downregulating TXNIP via the phosphatidylinositol-3-kinase (PI3K)/Akt pathway. Our results suggest that n-3 PUFA-mediated insulin sensitivity is at least partly associated with inflammasome inhibition in pre-adipocytes. Our findings highlight the potential clinical use of dietary n-3 PUFAs in the prevention or intervention of T2D and other NLRP3 inflammasome-driven inflammatory diseases.