Exercise Training-Induced PPARβ Increases PGC-1α Protein Stability and Improves Insulin-Induced Glucose Uptake in Rodent Muscles

Ju-Sik Park,Jin-Ho Koh,Kijin Kim,John O Holloszy

doi:10.3390/nu12030652

Ju-Sik Park, Jin-Ho Koh + Show 2 more

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https://doi.org/10.3390/nu12030652

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Abstract

This study aimed to investigate the long-term effects of training intervention and resting on protein expression and stability of peroxisome proliferator-activated receptor β/δ (PPARβ), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α), glucose transporter type 4 (GLUT4), and mitochondrial proteins, and determine whether glucose homeostasis can be regulated through stable expression of these proteins after training. Rats swam daily for 3, 6, 9, 14, or 28 days, and then allowed to rest for 5 days post-training. Protein and mRNA levels were measured in the skeletal muscles of these rats. PPARβ was overexpressed and knocked down in myotubes in the skeletal muscle to investigate the effects of swimming training on various signaling cascades of PGC-1α transcription, insulin signaling, and glucose uptake. Exercise training (Ext) upregulated PPARβ, PGC-1α, GLUT4, and mitochondrial enzymes, including NADH-ubiquinone oxidoreductase (NUO), cytochrome c oxidase subunit I (COX1), citrate synthase (CS), and cytochrome c (Cyto C) in a time-dependent manner and promoted the protein stability of PPARβ, PGC-1α, GLUT4, NUO, CS, and Cyto C, such that they were significantly upregulated 5 days after training cessation. PPARβ overexpression increased the PGC-1α protein levels post-translation and improved insulin-induced signaling responsiveness and glucose uptake. The present results indicate that Ext promotes the protein stability of key mitochondria enzymes GLUT4, PGC-1α, and PPARβ even after Ext cessation.

Highlights

Fatty acid and glucose are the primary energy sources used during skeletal muscle contraction.During exercise, these sources must be supplied to myocytes to regulate muscle contraction in accordance with the intensity and duration of exercise, and the capacity of glucose uptake and fatty acid oxidation in the muscle adaptively increases in response to a bout of exercise
glucose transporter type 4 (GLUT4) and mitochondrial enzymes are the primary factors determining the rate of glucose and fatty acid utilization in skeletal muscles
A cardinal adaptation to endurance Exercise training (Ext) is an increase in the the biogenesis of mitochondrial enzymes and GLUT4 in skeletal muscles, increasing the potential for biogenesis of mitochondrial enzymes and GLUT4 in skeletal muscles, increasing the potential for glucose and fatty acid metabolism during Ext and better disposal capacity of circulating glucose and glucose and fatty acid metabolism during Ext and better disposal capacity of circulating glucose and fatty acid in the resting state

Summary

Introduction

Fatty acid and glucose are the primary energy sources used during skeletal muscle contraction During exercise, these sources must be supplied to myocytes to regulate muscle contraction in accordance with the intensity and duration of exercise, and the capacity of glucose uptake and fatty acid oxidation in the muscle adaptively increases in response to a bout of exercise. The energy-generating capacity of the mitochondria with substrates, such as glucose and fatty acids, influence glucose uptake and fatty acid oxidation levels, and the expression levels and half-life of mitochondrial enzymes are reportedly differently regulated [6,7], indicating that protein stability is different during and after Ext. A bout of exercise upregulates GLUT4 [3], albeit not to peak expression levels. Mitochondria are not completely adapted following a single bout of exercise [7]

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