Exercise mitigates obesity-associated pathologies; however, there is controversy regarding optimal exercise interventions. Autophagy, is known to decrease during obesity and is an important moderator for exercise adaptations. Purpose: To investigate individual and combined effects of different exercise interventions and autophagy inhibition on exercise adaptations during obesity. Methods: C57BL/6J mice initiated 45% high fat diet at 8 weeks of age. After 6 weeks of diet, animals were divided into moderate (MOD) or high intensity interval training interventions (HIIT), animals were further divided into autophagy inhibition or vehicle conditions (n ¼ ۱۰/group). Animals exercised and autophagy was inhibited 3X/ week by NSC185058 injections, thereby blocking autophagosome formation. Interventions continued for 4 weeks. Results: High fat diet impaired glucose handling ~17%; exercise interventions normalized glucoregulation to prehigh fat diet levels, without differences between any interventions. High fat diet induced ~25% decrease in aerobic capacity, which returned to baseline after exercise interventions, with no differences between any interventions. No effects of autophagy inhibition were noted. Conclusions: HIIT and MOD training confer similar health-related adaptations.

Introduction

Obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM) remain significant maladies in Western society.1 Insulin medication costs have more than doubled, causing significant economic burdens and a reduction in overall quality of life for millions of patients.2 Exercise is known to decrease T2DM-associated insulin resistance (IR) and mortality regardless of weight loss.3 Recently, controversy surrounding the relative effectiveness of high intensity interval training (HIIT) compared to moderate intensity continuous training (MOD) has emerged.4 HIIT has become exponentially more popular over the past decade, finishing in the top three fitness trends in each of the last five years.5 Clinically, HIIT has become increasingly widespread as an exercise intervention across a greater breadth of populations, including those with metabolic impairments.4,6–۹ More so, recent meta-analyses suggest HIIT to be more effective compared to traditional moderate intensity continuous training (MOD) to improve insulin sensitivity.10 However, mechanisms that may correspond to the purported augmented benefits have yet to be elucidated. More so, it is difficult to draw strong conclusions regarding any potential additional benefits associated with HIIT compared to MOD, as many “comparative” protocols in the past did not match total work completed or average intensity of exercise.7,11,12 One cellular mechanism recently implicated in the development of exercise adaptations is autophagy.13–۱۵ Autophagy is a process that removes dysfunctional cellular components by sequestering organelles within an autophagosome and degrading them by lysosomal reaction.16 Previous research has demonstrated reductions in autophagy during IR.17,18 and transgenic models blocking autophagy initiation demonstrate diminished glucose handling capacity compared to healthy controls.19 Additionally, inhibition of Beclin-mediated autophagy impairs exercise training adaptations in otherwise healthy mice.20 Conversely, exercise interventions are known to increase autophagy.20–۲۲ Yet, the precise stimuli needed to activate autophagy with exercise training and the subsequent effects on IR remain uninvestigated, specifically the exercise intensity or volume necessary to induce adaptations.