TIR-Domain-Containing Adaptor-Inducing Interferon-β (TRIF) Is Involved in Glucose Metabolism in Adipose Tissue through the Insulin/AKT Signaling Pathway

• Published in: International journal of endocrinology Vol. 2020; no. 2020; pp. 1 - 9
• Main Authors: Yang, Junling, Fukuchi, Ken-Ichiro
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 09.12.2020; Hindawi; John Wiley & Sons, Inc; Hindawi Limited; Wiley
• Subjects: Adipocytes; Adipose tissues; Biological response modifiers; Blood sugar monitoring; Body fat; Cardiovascular disease; Cytokines; Development and progression; Dextrose; Diabetes; Endocrinology; Genetic research; Glucose; Glucose metabolism; Inflammation; Insulin; Insulin resistance; Interferon; Kinases; Metabolic disorders; Obesity; Pathogens; Plasma; Type 2 diabetes; St Louis Missouri; United States > US; Pittsburgh Pennsylvania
• ISSN: 1687-8337; 1687-8345
• DOI: 10.1155/2020/6942307

Obesity significantly increases the risk of developing type 2 diabetes mellitus and other metabolic diseases. Obesity is associated with chronic low-grade inflammation in white adipose tissues, which is thought to play an essential role in developing insulin resistance. Many lines of evidence indicate that toll-like receptors (TLRs) and their downstream signaling pathways are involved in development of chronic low-grade inflammation and insulin resistance, which are associated with obesity. Mice lacking molecules positively involved in the TLR signaling pathways are generally protected from high-fat diet-induced inflammation and insulin resistance. In this study, we have determined the effects of genetic deficiency of toll/interleukin-1 receptor-domain-containing adaptor-inducing interferon-β (TRIF) on food intake, bodyweight, glucose metabolism, adipose tissue macrophage polarization, and insulin signaling in normal chow diet-fed mice to investigate the role of the TRIF-dependent TLR signaling in adipose tissue metabolism and inflammation. TRIF deficiency (TRIF−/−) increased food intake and bodyweight. The significant increase in bodyweight in TRIF−/− mice was discernible as early as 24 weeks of age and sustained thereafter. TRIF−/− mice showed impaired glucose tolerance in glucose tolerance tests, but their insulin tolerance tests were similar to those in TRIF+/+ mice. Although no difference was found in the epididymal adipose mass between the two groups, the percentage of CD206+ M2 macrophages in epididymal adipose tissue decreased in TRIF−/− mice compared with those in TRIF+/+ mice. Furthermore, activation of epididymal adipose AKT in response to insulin stimulation was remarkably diminished in TRIF−/− mice compared with TRIF+/+ mice. Our results indicate that the TRIF-dependent TLR signaling contributes to maintaining insulin/AKT signaling and M2 macrophages in epididymal adipose tissue under a normal chow diet and provide new evidence that TLR4-targeted therapies for type 2 diabetes require caution.