Depot-specific adaption of adipose tissue for different exercise approaches in high-fat diet/streptozocin-induced diabetic mice.

Background: Adipose tissue pathology plays a crucial role in the pathogenesis of type 2 diabetes mellitus. Understanding the impact of exercise training on adipose tissue adaptation is of paramount importance in enhancing metabolic health. In this study, we aimed to investigate the effects of various exercise modalities on three distinct adipose tissue depots, namely, interscapular brown adipose tissue (iBAT), subcutaneous white adipose tissue (sWAT), and epididymal white adipose tissue (eWAT), in a murine model of diabetes. Methods: Male C57BL/6J mice received a 12-week high-fat diet and a single injection of streptozotocin, followed by an 8-week exercise intervention. The exercise intervention included swimming, resistance training, aerobic exercise, and high-intensity interval training (HIIT). Results: We found that exercise training reduced body weight and body fat percentage, diminished adipocyte size and increased the expression of mitochondria-related genes (PGC1, COX4, and COX8B) in three adipose tissue depots. The effects of exercise on inflammatory status include a reduction in crown-like structures and the expression of inflammatory factors, mainly in eWAT. Besides, exercise only induces the browning of sWAT, which may be related to the expression of the sympathetic marker tyrosine hydroxylase. Among the four forms of exercise, HIIT was the most effective in reducing body fat percentage, increasing muscle mass and reducing eWAT adipocyte size. The expression of oxidative phosphorylation and thermogenesis-related genes in sWAT and eWAT was highest in the HIIT group. Conclusion: When targeting adipose tissue to improve diabetes, HIIT may offer superior benefits and thus represents a more advantageous choice.

IFN-γ blockade after genetic inhibition of PD-1 aggravates skeletal muscle damage and impairs skeletal muscle regeneration.

BACKGROUND: Innate immune responses play essential roles in skeletal muscle recovery after injury. Programmed cell death protein 1 (PD-1) contributes to skeletal muscle regeneration by promoting macrophage proinflammatory to anti-inflammatory phenotype transition. Interferon (IFN)-γ induces proinflammatory macrophages that appear to hinder myogenesis in vitro. Therefore, we tested the hypothesis that blocking IFN-γ in PD-1 knockout mice may dampen inflammation and promote skeletal muscle regeneration via regulating the macrophage phenotype and neutrophils. METHODS: Anti-IFN-γ antibody was administered in PD-1 knockout mice, and cardiotoxin (CTX) injection was performed to induce acute skeletal muscle injury. Hematoxylin and eosin (HE) staining was used to view morphological changes of injured and regenerated skeletal muscle. Masson's trichrome staining was used to assess the degree of fibrosis. Gene expressions of proinflammatory and anti-inflammatory factors, fibrosis-related factors, and myogenic regulator factors were determined by real-time polymerase chain reaction (PCR). Changes in macrophage phenotype were examined by western blot and real-time PCR. Immunofluorescence was used to detect the accumulation of proinflammatory macrophages, anti-inflammatory macrophages, and neutrophils. RESULTS: IFN-γ blockade in PD-1 knockout mice did not alleviate skeletal muscle damage or improve regeneration following acute cardiotoxin-induced injury. Instead, it exacerbated skeletal muscle inflammation and fibrosis, and impaired regeneration via inhibiting macrophage accumulation, blocking macrophage proinflammatory to anti-inflammatory transition, and enhancing infiltration of neutrophils. CONCLUSION: IFN-γ is crucial for efficient skeletal muscle regeneration in the absence of PD-1.

Beneficial Effects and Potential Mechanisms of Tai Chi on Lower Limb Osteoarthritis: A Biopsychosocial Perspective.

Lower limb osteoarthritis (OA) is a chronic, multifactorial disease characterized by impaired physical function, chronic pain, compromised psychological health and decreased social functioning. Chronic inflammation plays a critical role in the pathophysiology of OA. Tai Chi is a type of classical mind-body exercise derived from ancient Chinese martial arts. Evidence supports that Tai Chi has significant benefits for relieving lower limb OA symptoms. Using a biopsychosocial framework, this review aims to elucidate the beneficial effects of Tai Chi in lower limb OA and disentangle its potential mechanisms from the perspective of biology, psychology, and social factors. Complex biomechanical, biochemical, neurological, psychological, and social mechanisms, including strengthening of muscles, proprioception improvement, joint mechanical stress reduction, change of brain activation and sensitization, attenuation of inflammation, emotion modulation and social support, are discussed.

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

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.