S616 Vol. 49 No. 5 Supplement MEDICINE & SCIENCE IN SPORTS & EXERCISE® F-01 Highlighted Symposium ‑ Move to the MYOD1. To identify genome-wide binding sites for BMAL1:CLOCK and MYOD1 we performed chromatin immunoprecipitation and ultra-high throughput sequencing Rhythm: Circadian Orchestration of (ChIP-Seq) in wildtype C57BL6 quadriceps and C2C12 myotubes. HOMER Exercise and Muscle Biology software was utilized for Next-Gen sequencing analysis. RESULTS: We utilized a bioinformatics approach to identify Tcap as a skeletal muscle specific, circadian gene. Friday, June 2, 2017, 1:00 PM ‑ 3:00 PM Interestingly, we found that MYOD1 transactivates Tcap in a synergistic fashion with Room: 201 BMAL1:CLOCK and enhances T-cap’s circadian amplitude. Three e-box elements within the Tcap promoter are required for cooperativity between the clock factors and 2844 Chair: John C. Quindry, FACSM. University of Montana, MYOD1. ChIP-Seq analysis in skeletal muscle indicated that MYOD1 targets a large Missoula, MT. subset of the skeletal muscle circadian transcriptome. CONCLUSION: These findings (No relationships reported) support the hypothesis that MYOD1 is a key regulator of circadian gene expression in skeletal muscle. 2845 June 2 1:10 PM ‑ 1:40 PM June 2 2:40 PM ‑ 3:00 PM Keynote - Can Circadian Clocks Anticipate Periods of Overall Discussion Activity and Energetic Demand? Martin E. Young. University of Alabama at Birmingham, Birmingham, AL. Reported Relationships: M.E. Young: Consulting Fee; Merck. F-08 Basic Science World Congress ‑ Thematic Poster ‑ Neuroplasticity and Cerebral 2846 June 2 1:40 PM ‑ 1:55 PM Perfusion Does the Cardiomyocyte Circadian Clock Influence Friday, June 2, 2017, 1:00 PM ‑ 3:00 PM Size of the Heart? Room: 304 Graham R. McGinnis, John C. Chatham, Martin E. Young. University of Alabama at Birmingham, Birmingham, AL. 2875 Chair: Hirofumi Tanaka, FACSM. University of Texas at (No relationships reported) Austin, Austin, TX. (No relationships reported) Circadian clocks, driven by the transcription factors Clock (circadian locomotor output cycles kaput) and Bmal1 (brain and muscle arnt-like 1), are sophisticated mechanisms 2876 Board #1 June 2 1:00 PM ‑ 3:00 PM that regulate 24-hr rhythms in numerous physiological processes ranging from gene expression to behavior. The cardiomyocyte clock has been shown to regulate cardiac Habitual Physical Activity Mitigates the Adverse Effects metabolism and function, and its disruption decreases lifespan. However, the role of of Metabolic Syndrome on Arterial Stiffness and the circadian clock in regulating cardiomyocyte growth remains unknown. PURPOSE: Cerebral White Matter Integrity To determine the role of the cardiomyocyte circadian clock in regulating hypertrophic Evan P. Pasha, Alex C. Birdsill, Stephanie Oleson, Andreana P. growth of the heart. METHODS: We used mice with genetically disrupted clocks specifically within the heart (Cardiomyocyte-specific Bmal1 Knockout; CBK) and Haley, Hirofumi Tanaka, FACSM. The University of Texas at littermate control mice (CON) to investigate the role of the cardiomyocyte circadian Austin, Austin, TX. (Sponsor: Hirofumi Tanaka, FACSM) clock on cardiac growth/size. Signaling was assessed through Western blotting, Email: [email protected] while rates of protein synthesis were measured using radiolabeled tracers (both in (No relationships reported) vivo and ex vivo). Rapamycin feeding (14 ppm and 42 ppm, 10 days) was utilized to pharmacologically inhibit mTOR. RESULTS: We found that disruption of the PURPOSE: Metabolic syndrome (MetS) adversely affects the vasculature and cerebral cardiomyocyte circadian clock leads to increased activation of the Akt/mTOR/S6 white matter integrity. Arterial stiffening has been associated with diminished cerebral signaling axis in the heart. Rates of protein synthesis displayed a diurnal rhythm in white matter integrity. Habitual physical activity (PA) can ameliorate components CON mice (highest at ZT0) in vivo, which was chronically elevated in CBK mice; of MetS and subsequently affect arterial stiffening and white matter integrity. Our the same genotype effect was seen in ex vivo perfused hearts. CBK hearts exhibited aim was to determine the role of habitual PA on mitigating the adverse influence of increased heart size (relative to CON hearts), which was normalized by rapamycin MetS on arterial stiffness and cerebral white matter integrity. METHODS: Sixty-six feeding. CONCLUSION: Genetic disruption of the cardiomyocyte circadian clock middle-aged adults (40-62 years) composed of 27 healthy, 18 sedentary MetS (Sed leads to chronic activation of the Akt/mTOR/S6 signaling axis in the heart, associated MetS), and 21 physically active MetS individuals (Active MetS) were studied. Carotid with increased protein synthesis and size. artery stiffness was assessed via simultaneous ultrasound and tonometry. Cerebral white matter integrity was measured using diffusion tensor imaging through metrics of 2847 June 2 1:55 PM ‑ 2:25 PM fractional anisotropy (FA) and mean diffusivity (MD). RESULTS: Carotid β-stiffness index in Active MetS was lower than Sed MetS but was not different from Healthy Keynote - Time of Exercise as a Muscle Clock Setter controls (6.6±1.5, 7.7±2.1, and 5.6±1.6 au, p=0.001). The same group pattern was Karyn A. Esser, FACSM. University of Florida, Gainesville, FL. observed with white matter microstructural integrity in regions of interest (ROIs). (No relationships reported) Mean ROI FA was significantly greater in Active MetS compared with Sed MetS but was not different from Healthy controls (0.54±0.03, 0.51±0.02, and 0.53±0.02 au, p=0.012). Mean ROI MD was significantly lower in Active MetS compared with Sed MetS but was not different from Healthy controls (0.85±0.05, 0.89±0.05, and 2848 June 2 2:25 PM ‑ 2:40 PM 0.86±0.05 mm2/s, p=0.019). CONCLUSION: Middle-aged individuals with MetS Regulation of the Skeletal Muscle Circadian who habitually perform PA demonstrated lower arterial stiffness and more favorable Transcriptome by the Master Myogenic Regulatory cerebral white matter integrity than their sedentary peers, indicating that habitual Factor, Myod1 exercise may be effective in mitigating the adverse effects of MetS on the vasculature and brain at midlife. Brian A. Hodge1, Xiping Zhang2, Karyn A. Esser, FACSM2. 1 2 This work was supported by grants from the NIH, NINDS (to APH) and the NSF (to Buck Institute for Research on Aging, Novato, CA. University AB). of Florida, Gainesville, FL. (No relationships reported) Molecular clocks are comprised of interlocking transcriptional:translational feedback loops that promote circadian rhythms in physiology through controlling downstream gene expression in a temporal and tissue-specific fashion. The mechanisms in which the core clock factors (ubiquitously expressed in all tissues) target skeletal muscle specific genes are poorly understood. PURPOSE: Here we investigate the role of the muscle specific factor MYOD1 in regulating skeletal muscle circadian gene FRIDAY, JUNE 2, 2017 FRIDAY, expression. METHODS: Dual-luciferase assays and real-time bioluminescence (Lumicycle) were performed in C2C12 myotubes to determine transcriptional responses and rhythmic expression patterns of the muscle specific circadian gene, Titin-cap (Tcap), with over expression of the core-clock genes BMAL1:CLOCK with ACSM May 30 – June 3, 2017 Denver, Colorado Official Journal of the American College of Sports Medicine Vol. 49 No. 5 Supplement S617 2877 Board #2 June 2 1:00 PM ‑ 3:00 PM 2879 Board #4 June 2 1:00 PM ‑ 3:00 PM Changes in Brain Perfusion Following Weight Loss are Effects Of Exercise-induced Hypohydration On Brain Associated with Changes in Body Mass Index Structure And Function, A MRI Study Chelsea M. Stillman1, Jennifer C. Watt2, Renee J. Rogers3, John X. r. Tan1, Ivan C. C. Low1, Mary C. Stephenson2, T. Kok2, M. Jakicic, FACSM3, Kirk I. Erickosn3. 1University of Pittsburgh Heinrich W. Nolte3, T. W. Soong1, Jason K. W. Lee, FACSM4. School of Medicine, Pittsburgh, PA. 2University of Pittsbugh, 1National University of Singapore, Singapore, Singapore. Pittsburgh, PA. 3University of Pittsburgh, Pittsburgh, PA. 2Agency for Science, Technology Research, Singapore, (Sponsor: John Jakicic, FACSM) Singapore. 3ERGOnomics TECHnologies, Pretoria, South (No relationships reported) Africa. 4DSO National Laboratories, Singapore, Singapore. Email: [email protected] PURPOSE: Being overweight or obese, defined as having a body mass index (BMI) (No relationships reported) of 25 or greater, is associated with brain hypoperfusion. However, it is unknown to what extent obesity-related hypoperfusion can be reversed following weight loss. Hypohydration exceeding 2% body mass is known to impair endurance capacity. It Further, the relative contributions of diet and physical activity (PA) on brain perfusion is hypothesized that the central nervous system, specifically the brain, is negatively are poorly understood. The aim of the present study was to examine changes in brain affected by hypohydration, leading to a decline in endurance capacity. perfusion following weight loss, and to relate changes in perfusion to changes in BMI. PURPOSE: METHODS: 121 healthy adults (M±SD = 44.3±8.6 years old; 95 female) completed To investigate the effects of exercise-induced hypohydration on the brain. a 12-month randomized controlled trial involving an energy restricted diet (diet-only), METHODS: a diet + 150 minutes of moderate intensity PA per week (Mod-PA), or diet and 250 Ten trained endurance