Exercise is a key component of the successful management of many obesity-related metabolic complications, including insulin resistance. Importantly, many of the beneficial metabolic effects of endurance exercise training are attributed to the most recent exercise session(s), rather than to adaptations resulting from prolonged training, or to improved "fitness", per se. Therefore, lifestyle interventions for obese, insulin resistant patients should be tailored to optimize the metabolic effects of the most recent exercise session(s). However, the "dose" of acute exercise (i.e., intensity, duration, energy expended) necessary to improve insulin sensitivity in obesity is not known, and the mechanisms responsible for this improvement are still poorly understood. The excessive fatty acid availability found in obese individuals is largely responsible for their suppressed insulin sensitivity. "Partitioning" of these fatty acids within the myocyte toward oxidation, storage, or accumulation of intracellular fatty acid intermediates (e.g., ceramide, diacylglyceride, fatty acyl-CoA), and the resultant activation of pro-inflammatory pathways (e.g., c-jun NH2-terminal kinase (JNK)) mediate this response. Our working hypothesis is: A single session of exercise in obese adults will improve insulin sensitivity the next day despite a persistent elevation in fatty acid availability and uptake, in part because acute exercise will partition fatty acids away from accumulation of fatty acid intermediates, and thereby reduce the activation of pro-inflammatory pathways. We will first compare the effect of different exercise intensities (50% vs. 65% VO2peak) and different levels of energy expenditure (200 vs 350kcal) of a single exercise session on insulin sensitivity and muscle fatty acid metabolism measured the day after exercise in obese adults [Specific Aim #1]. We hypothesize that expending 350 kcal during exercise at both 50% and 65% VO2peak (~60 and ~45 min of exercise, respectively), as well as expending 200 kcal during exercise at 65% VO2peak (~30min of exercise) will be sufficient to alter fatty acid partitioning, reduce pro-inflammatory stress, and thereby improve insulin sensitivity the next day, but expending 200 kcal during exercise at 50% VO2peak (~40min of exercise) will not. To more definitively test the contribution of exercise-induced alterations in fatty acid partitioning on insulin sensitivity we will assess whether the minimum "dose" of exercise found in Specific Aim #1 protects against fatty acid-induced insulin resistance in obese adults [Specific Aim #2]. Finally, we will examine the cumulative effect of low doses of exercise (40 min of exercise at 50% VO2peak) performed over days, weeks, and months on insulin sensitivity, fatty acid partitioning, and activation of pro-inflammatory pathways [Specific Aim #3]. Findings from these studies will vastly improve our understanding about the regulation of insulin action and fatty acid partitioning after exercise in obesity. Moreover, these findings will provide valuable information for the development of lifestyle programs aimed at maximizing the key metabolic benefits of each exercise session in obese, insulin resistant patients.
Many of the beneficial metabolic effects of endurance exercise training are not due to adaptations to weeks, months, or even years of training, but rather much is due to the response to the most recent exercise session(s). Therefore, we contend that lifestyle interventions for obese individuals should be tailored to optimize the metabolic effects of the most recent exercise session(s). But the "dose" of exercise necessary to evoke these beneficial responses is not known, and the mechanisms responsible for these improvements are poorly understood. The findings from these studies will: 1) establish the minimum "dose" of a single exercise session necessary to improve insulin sensitivity the next day in obese adults, 2) characterize the underlying metabolic factors responsible for the improvement in insulin sensitivity, and 3) assess the cumulative metabolic adaptations that occur over days, weeks, and months of a low-intensity/low-volume lifestyle exercise program. Findings from these studies will provide valuable information for the development of lifestyle programs aimed at maximizing the key metabolic health benefits of each exercise session in obese patients.
|Van Pelt, D W; Newsom, S A; Schenk, S et al. (2015) Relatively low endogenous fatty acid mobilization and uptake helps preserve insulin sensitivity in obese women. Int J Obes (Lond) 39:149-55|
|Newsom, Sean A; Everett, Allison C; Park, Sanghee et al. (2015) Lipid mixtures containing a very high proportion of saturated fatty acids only modestly impair insulin signaling in cultured muscle cells. PLoS One 10:e0120871|
|Caruso, Michael; Ma, Danjun; Msallaty, Zaher et al. (2014) Increased interaction with insulin receptor substrate 1, a novel abnormality in insulin resistance and type 2 diabetes. Diabetes 63:1933-47|
|Nelson, Rachael K; Horowitz, Jeffrey F (2014) Acute exercise ameliorates differences in insulin resistance between physically active and sedentary overweight adults. Appl Physiol Nutr Metab 39:811-8|
|Boon, James; Hoy, Andrew J; Stark, Romana et al. (2013) Ceramides contained in LDL are elevated in type 2 diabetes and promote inflammation and skeletal muscle insulin resistance. Diabetes 62:401-10|
|Nelson, Rachael K; Horowitz, Jeffrey F; Holleman, Robert G et al. (2013) Daily physical activity predicts degree of insulin resistance: a cross-sectional observational study using the 2003-2004 National Health and Nutrition Examination Survey. Int J Behav Nutr Phys Act 10:10|
|Newsom, Sean A; Everett, Allison C; Hinko, Alexander et al. (2013) A single session of low-intensity exercise is sufficient to enhance insulin sensitivity into the next day in obese adults. Diabetes Care 36:2516-22|
|Watt, M J; Barnett, A C; Bruce, C R et al. (2012) Regulation of plasma ceramide levels with fatty acid oversupply: evidence that the liver detects and secretes de novo synthesised ceramide. Diabetologia 55:2741-6|
|Newsom, Sean A; Schenk, Simon; Li, Minghua et al. (2011) High fatty acid availability after exercise alters the regulation of muscle lipid metabolism. Metabolism 60:852-9|
|Cornford, Andrea S; Barkan, Ariel L; Horowitz, Jeffrey F (2011) Rapid suppression of growth hormone concentration by overeating: potential mediation by hyperinsulinemia. J Clin Endocrinol Metab 96:824-30|
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