Central Resistin/TLR4 Impairs Adiponectin Signaling, Contributing to Insulin and FGF21 Resistance

• DOI: 10.2337/db15-1029
• Publication Date: 2016-01-07T04:04:30Z
• Authors: Yacir Benomar; Hamza Amine; Délphine Crépin; Sarah Al Rifai; Laure Riffault; Arieh Gertler; Mohammed Taouis
• Keywords: Resistin; FGF21; Adiponectin receptor 1

Adiponectin, an insulin-sensitizing hormone, and resistin, known to promote insulin resistance, constitute a potential link between obesity type 2 diabetes. In addition, fibroblast growth factor (FGF)21 has effects similar those of adiponectin in regulating glucose lipid metabolism sensitivity. However, the interplay adiponectin, FGF21, resistin signaling pathways during onset resistance is unknown. Here, we investigated whether central promotes through impairment FGF21 signaling. We show that chronic intracerebroventricular infusion downregulated both hypothalamic hepatic APPL1, key protein signaling, associated with decreased Akt-APPL1 interaction increased Akt association its endogenous inhibitor tribbles homolog 3. Resistin treatment also plasma levels reduced peripheral expression receptors. Additionally, report receptor components hypothalamus tissues, promoting resistance. Interestingly, were abolished TLR4 knockout mice neuronal cells expressing siRNAs. Our study reveals novel mechanism orchestrated by resistin-TLR4 pathway impairs