Intermittent fasting therapy promotes insulin sensitivity by inhibiting NLRP3 inflammasome in rat model.

Abstract

Substantial studies have demonstrated that fasting therapy (FT) can inhibit the inflammatory response and improve insulin resistance (IR); however, the underlying mechanisms are still unclear. This study aimed to explore the related mechanisms of intermittent FT for the treatment of IR. A rat IR model was established through collaboration of a high-fat diet with streptozotocin (STZ) injection. 8 rats were treated with intermittent FT. A positive control group was treated with metformin (MET). Mouse 3T3-L1 pre-adipocytes were cultured and induced into adipocytes in vitro, and were used as the cellular IR model. Blood insulin, glucose, and homeostatic model assessment (HOMA)-IR index were determined. Enzyme-linked immunosorbent assay (ELISA) and western blotting were used to detect inflammatory markers. Oil Red O staining determined the lipid accumulation. An NLRP3 inflammasome agonist served to investigate the effects of FT on IR in 3T3-L1 adipocytes. The high levels of blood insulin, glucose, and HOMA-IR induced by high-fat diet and STZ were significantly decreased by FT. The FT also reduced the level of C-reactive protein (CRP), interleukin (IL)-1β, IL-18, caspase-1, and increased the expression of glucose transporter 1 (GLUT1), insulin receptor substrate 1 (IRS1), and IRS2 in both the rat models and 3T3-L1 adipocytes. In addition, FT significantly relieved lipid accumulation in the liver of rats. Application of NLRP3 inflammasome agonist weakened the effect of FT on IR in the IR 3T3-L1 adipocytes. These results suggest that FT can ameliorate the high-fat diet-and STZ-induced IR in rats through inhibition of NLRP3 inflammasome.