Insulin sensitivity and fatty acid partitioning in skeletal muscle after exercise

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 DESCRIPTION (provided by applicant): Exercise is a key component in the prevention and treatment of many obesity-related metabolic complications, including insulin resistance and type 2 diabetes. High intensity interval training (HIIT), which alternates brief high-intensity efforts ith brief recovery periods, has been found to markedly improve clinical markers of metabolic health (meal tolerance, 24h glucose). Therefore, HIIT may be considered an effective and time- efficient alternative to "conventional" exercise. Importantly, HIIT has also been found to be safe and well tolerated in obese and type 2 diabetic patients. The exercise stimulus of HIIT is obviously very different from conventional exercise, and can yield unique adaptions. However, mechanisms underlying HIIT-induced improvements in metabolic health remain poorly understood. In addition, variations in the main components of HIIT (# of intervals, exercise time, energy expended) may induce very different metabolic outcomes, yet a systematic assessment of deviations in these parameters has not been conducted. Furthermore, while available evidence clearly demonstrates HIIT can induce impressive health benefits after a few to several weeks of training, the ability/willingness of obese adults to adhere to a long-term HIIT program is not known. Our overall objectives are to: 1) comprehensively assess putative mechanisms underlying HIIT-induced improvements in insulin resistance at the whole-body, tissue, and cellular levels, 2) systematically evaluate the impact of different "doses" of HIIT that may be optimal for improving metabolic health in obese adults, and 3) assess the ability/willingness of obese subjects to adhere to long-term HIIT programs. In Specific Aim #1, we will examine the effects of 3 months of HIIT (10 x 1min at ~90%maximal heart rate [HRmax]; 4d/wk) on changes in key clinical health outcomes (e.g., insulin resistance, 24h glucose control, hepatic lipid accumulation, blood lipid profile) in obese adults with impaired glucose tolerance. We will also compare HIIT with "conventional" exercise-training involving steady-state exercise for 45 min at 60-70%HRmax (which represents a common exercise prescription for health and fitness). Specific Aim #2 will determine factors underlying the improvements in insulin resistance (e.g., reduced lipid accumulation in skeletal muscle, lower macrophage infiltration and markers of inflammation in adipose tissue and skeletal muscle, and/or enhanced insulin signaling). Specific Aim #3 will address important clinical/applied issues regarding the optimization of HIIT by systematically evaluating the effects of the number of intervals, exercise time, and energy expended during HIIT on insulin resistance - and we will also assess the ability/willingness of obese adults with impaired glucose tolerance to adhere to HIIT programs for up to 1 year. Findings from these studies will greatly expand our understanding about the effects of HIIT on metabolic health, and will provide tremendously valuable information for the design of programs aimed at maximizing key metabolic benefits of exercise.