This proposal outlines a career development plan to help Dr. Audrey Bergouignan complete her postdoctoral training and establish an independent research program focused on the physiopathology of sedentary behaviors. Her training will be conducted in a multidisciplinary group of scientists with research expertise in obesity, metabolism, whole-body and mitochondrial physiology, biochemistry and biostatistics. Her mentor, Dr. Daniel Bessesen, has an extensive experience with trainees that will be complemented by those in her advisory team, Drs. Reusch, Murphy, Melanson and Pan. Collectively, this team will provide an outstanding training environment that will allow her to fil critical gaps in her toolbox needed to use an integrative approach from whole-body to tissue, cell, protein and gene levels to study mechanisms underlying the causal relationship between sedentary behaviors and adverse metabolic health outcomes. This award will also solidify her knowledge in biostatistics and ability to conduct clinical research studies. During the training phase of this award, she will strengthen her scholarly activities, establish important collaborations, and acquire critical data that will ensure her successful transition to independence. Rational: There is emerging evidence from population studies that time spent in sedentary behaviors is associated with all-cause mortality including obesity, type 2 diabetes, and cardiovascular diseases. Importantly, these associations are independent of time spent in exercise. Frequent interruptions to sedentary time are however beneficially associated with metabolic health outcomes, even in individuals who exercise regularly. Our hypothesis is that breaking-up prolonged sitting improves metabolic health. Our goal is to use integrative approach to understand the biological mechanisms that underlie associations of frequent interruptions of prolonged sitting with improved metabolic health outcomes. Design: A 24-hr study will first determine in overweight adults the effects of breaking-up prolonged sitting on whole-body substrate use and postprandial glucose and insulin concentrations, two core components of metabolic health. The first study will provide the applicant with training experiences and preliminary data to perform the more definitive study proposed in the R00 phase. The effects of 4 weeks of microbursts of activity will be compared with traditional caloric equivalent exercise training on plasma cardiometabolic markers, index of metabolic health. The underlying mechanisms, i.e. whole body substrate use, dietary fat oxidation and trafficking in skeletal muscle lipid fractions and mitochondrial function will be further delineated in association with insulin sensitivity. Relevance: We believe that the proposed studies will provide an initial evidence base for the health benefits of breaking up prolonged sitting with short bursts of activity. This innovative strategy may be more effective at combating the adverse effects of sedentary behaviors than more traditional approaches.

Public Health Relevance

Although public-health recommendations to engage in moderate-to-vigorous physical activity (at least 30min, 5 days / week) have been widely promulgated by the government, most people are physically inactive. Sedentary behaviors, like time spent sitting, are associated with serious implications on metabolic health, indicating that even in individuals who regularly exercise a reduction in time spent sitting can confer health benefits. This project proposes to test the effect of interruptions of prolonged sitting by microbursts of activity, an intervention likely easier to implement in daily life of at-risk populaion, on metabolic health.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Career Transition Award (K99)
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Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Bremer, Andrew
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University of Colorado Denver
Internal Medicine/Medicine
Schools of Medicine
United States
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Foright, R M; Presby, D M; Sherk, V D et al. (2018) Is regular exercise an effective strategy for weight loss maintenance? Physiol Behav 188:86-93
Creasy, Seth A; Rynders, Corey A; Bergouignan, Audrey et al. (2018) Free-Living Responses in Energy Balance to Short-Term Overfeeding in Adults Differing in Propensity for Obesity. Obesity (Silver Spring) 26:696-702
Rynders, Corey A; Schmidt, Stacy L; Bergouignan, Audrey et al. (2018) Effects of short-term sex steroid suppression on dietary fat storage patterns in healthy males. Physiol Rep 6:
Rynders, Corey A; Bergouignan, Audrey; Kealey, Elizabeth et al. (2017) Ability to adjust nocturnal fat oxidation in response to overfeeding predicts 5-year weight gain in adults. Obesity (Silver Spring) 25:873-880
Bergouignan, Audrey; Legget, Kristina T; De Jong, Nathan et al. (2016) Effect of frequent interruptions of prolonged sitting on self-perceived levels of energy, mood, food cravings and cognitive function. Int J Behav Nutr Phys Act 13:113