Date of Award

5-2020

Document Type

Campus Access Thesis

Degree Name

Master of Science (MS)

Department

Exercise and Health Science

First Advisor

Kai Zou

Second Advisor

Huimin Yan

Third Advisor

Tongjian You

Abstract

High intensity interval training (HIIT) elicits analogous metabolic adaptations in skeletal muscle as continuous endurance training. Mitochondria play an integral role in skeletal muscle metabolism, insulin sensitivity and metabolic health. Mitochondrial quality control refers to the hierarchical network of interconnecting pathways (i.e., mitochondrial biogenesis, autophagy, mitophagy, fusion and fission) to optimize mitochondrial function. However, a complete profile of regulatory proteins of mitochondrial quality control in response to HIIT and how the alterations of these processes are associated with HIIT-induced metabolic benefits have yet to be evaluated in the setting of diet-induced obesity. Therefore, the purpose of this thesis project was to examine the effects of 10-weeks of HIIT intervention on skeletal muscle mitochondrial quality control and whole-body glucose homeostasis in diet-induced obese mice.

Male C57/BL-6 mice were randomly assigned to a low-fat diet (LFD) and high-fat diet (HFD). After 10 weeks, mice fed with HFD were further divided into sedentary and HIIT groups and remained on HFD for an additional 10 weeks (n = 10/group). Graded exercise tests (GXT), glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were administered. HIIT protocol consisted of sessions three days a week for 10 weeks. For each session, mice ran at 90% maximal speed, running for 3-minutes of exercise followed by a 2-minute active recovery at 50% maximal speed. totaling 30 minutes. Expression of mitochondrial content, biogenesis, autophagy, mitophagy, and dynamics proteins were determined through immunoblots. One-way ANOVA was used to assess any between group differences.

Following 10 weeks of HIIT, animals fed with HFD exhibited an 11.2% improvement in exercise capacity and 16.7% greater p-AKT/AKT ratio (P < 0.05). HIIT significantly increased Drp1(ser637) phosphorylation and ratio of phospho-Drp1(ser637) to Drp1. when compared to HFD (26.3% and 28.3% respectively, P < 0.05). Additionally, HIIT group exhibited significantly increased skeletal muscle p62 protein content when compared to HFD (17.6%, P < 0.05). In conclusion, our study demonstrated that 10 weeks of HIIT partitioned into 30-minute sessions for 3 days/week is effective in improving skeletal muscle mitochondrial quality control in diet-induced obese mice through the alterations of skeletal muscle p62-regulated autophagy and Drp1¬-mediated mitochondrial fission.

Comments

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