Abstract
ObjectivesRegular physical exercise can improve insulin resistance in insulin target tissues. However, the mechanisms about the beneficial effect of exercise on insulin resistance are not yet fully resolved. This study was carried out to address whether insulin resistance improvement by exercise is involved in an anti-inflammatory pathway in the spleen in high-fat diet (HFD) feeding mice.MethodsMale C57Bl/6J mice with or without subdiaphragmatic vagotomy (sVNS) were subjected to medium-intensity treadmill exercise during HFD feeding. Glucose tolerance test and insulin tolerance test were detected, and spleen acetylcholine level, choline acetyltransferase activity (ChAT), protein kinase C (PKC) and tumor necrosis factor-alpha (TNF-α) were assayed.ResultsWe found that exercise significantly improves HFD-induced glucose intolerance and insulin resistance, along with an increase in acetylcholine level, ChAT activity, and PKC activity, and decrease in TNF-α level in the system and the spleen from HFD-fed mice. However, sVNS abolished the beneficial effect of exercise on glucose intolerance and insulin resistance, decreased acetylcholine level, ChAT activity, and PKC activity, and increase TNF-α level of the spleen in HFD-mice exercise intervention.ConclusionsThese data reveal that the prevention of HFD-associated insulin resistance by exercise intervention involves reducing splenic TNF-α level, which is mediated by cholinergic anti-inflammatory activity via influencing PKC activity, ChAT activity, and acetylcholine concentration in mice spleen.
Highlights
Insulin resistance is considered a pathological condition in which cells do not react efficiently to insulin stimulation
Exercise ameliorates high-fat diet (HFD)‐induced insulin resistance in male mice Male C57Bl/6J mice were subjected to medium-intensity treadmill exercise or no exercise during HFD feeding for Exercise reduces TNF‐α level and increases the acetylcholine level in the spleen According to reports, in the spleen, choline acetyltransferase + T cells (ChAT + T cells) can synthesize and release acetylcholine in response to outgoing vagus nerve signals
We found that HFD consumption effectively reduces acetylcholine level (p < 0.05) (Fig. 2A), choline acetyltransferase activity (ChAT) activity (p < 0.05) (Fig. 2B), and protein kinase C (PKC) activity (p < 0.05) (Fig. 2C), and simultaneously increases TNF-α level compared to standard chow-fed control (p < 0.05) (Fig. 2D)
Summary
Insulin resistance is considered a pathological condition in which cells do not react efficiently to insulin stimulation It is a decisive risk factor leading to diabetes, Huang et al Diabetol Metab Syndr (2021) 13:124 mutation, endoplasmic reticulum stress, inflammation, oxidative stress, and mitochondrial dysfunction, which lead to damaged insulin signaling pathways and insulin resistance in some tissues, such as the liver, skeletal muscle, adipose tissue, and heart [1, 5]. Splenectomy abrogates exercise control of serum TNF-α level in the context of endotoxemia [16] It is unknown whether the beneficial effect of exercise on insulin resistance involves in TNF-α level regulated by vagus nerverelated anti-inflammatory activity in the spleen. This study was carried out to address whether splenic TNF-α level regulated by vagus nerve-related anti-inflammatory activity contributes to exercise-associated insulin resistance improvement in HFD mice. The results achieved will be helpful to the in-depth understanding of the exact mechanism of exercise protecting against insulin resistance and aid in providing novel sight of therapeutic intervention for insulin resistance-related disease
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