HIIT Ameliorates Inflammation and Lipid Metabolism by Regulating Macrophage Polarization and Mitochondrial Dynamics in the Liver of Type 2 Diabetes Mellitus Mice

Abstract

High-intensity interval training (HIIT), a new type of exercise, can effectively prevent the progression of metabolic diseases. The aim of this study was to investigate the effects of HIIT on liver inflammation and metabolic disorders in type 2 diabetes mellitus (T2DM) mice induced by a high-fat diet (HFD) combined with streptozotocin (STZ) and to explore the possible mechanisms of macrophage polarization and mitochondrial dynamics. Our results showed that HIIT can increase fatty acid oxidation-related gene (PPARα, CPT1α, and ACOX1) mRNA levels and decrease adipogenesis-related gene (PPARγ) mRNA levels to improve liver metabolism in T2DM mice. The improvement of lipid metabolism disorder may occur through increasing liver mitochondrial biosynthesis-related genes (PGC-1α and TFAM) and restoring mitochondrial dynamics-related gene (MFN2 and DRP1) mRNA levels. HIIT can also reduce the mRNA levels of liver inflammatory factors (TNF-α, IL-6, and MCP-1) in T2DM mice. The reduction in liver inflammation may occur through reducing the expression of total macrophage marker (F4/80) and M1 macrophage marker (CD86) mRNA and protein and increasing the expression of M2 macrophage marker (CD163, CD206, and Arg1) mRNA and protein in the liver. HIIT can also increase the expression of insulin signaling pathway (IRS1, PI3K, and AKT) mRNA and protein in the liver of T2DM mice, which may be related to the improvements in liver inflammation and lipid metabolism. In conclusion, these results suggested that 8 weeks of HIIT can improve inflammation and lipid metabolism disorders in the liver of type 2 diabetes mellitus mice, macrophage M1/M2 polarization, and mitochondrial dynamics may be involved in this process.