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    Greater glucose uptake heterogeneity in knee muscles of old compared to young men during isometric contractions detected by [18F]-FDG PET/CT
    (Colorado State University. Libraries, 2014-05) Rudroff, Thorsten, author; Kindred, John H., author; Benson, John-Michael, author; Tracy, Brian L., author; Kalliokoski, Kari K., author; Frontiers Media S. A., publisher
    We used positron emission tomography/computed tomography (PET/CT) and [18F]-FDG to test the hypothesis that glucose uptake (GU) heterogeneity in skeletal muscles as a measure of heterogeneity in muscle activity is greater in old than young men when they perform isometric contractions. Six young (26 ± 6 years) and six old (77 ± 6 years) men performed two types of submaximal isometric contractions that required either force or position control. [18F]-FDG was injected during the task and PET/CT scans were performed immediately after the task. Within-muscle heterogeneity of knee muscles was determined by calculating the coefficient of variation (CV) of GU in PET image voxels within the muscles of interest. The average GU heterogeneity (mean ± SD) for knee extensors and flexors was greater for the old (35.3 ± 3.3%) than the young (28.6 ± 2.4%) (P = 0.006). Muscle volume of the knee extensors were greater for the young compared to the old men (1016 ± 163 vs. 598 ± 70 cm3, P = 0.004). In a multiple regression model, knee extensor muscle volume was a predictor (partial r = −0.87; P = 0.001) of GU heterogeneity for old men (R2 = 0.78; P < 0.001), and MVC force predicted GU heterogeneity for young men (partial r = −0.95, P < 0.001). The findings demonstrate that GU is more spatially variable for old than young men and especially so for old men who exhibit greater muscle atrophy.
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    ItemOpen Access
    Regulators of human white adipose browning: evidence for sympathetic control and sexual dimorphic responses to sprint interval training
    (Colorado State University. Libraries, 2014-03) Scalzo, Rebecca L., author; Peltonen, Garrett L., author; Giordano, Gregory R., author; Binns, Scott E., author; Klochak, Anna L., author; Paris, Hunter L. R., author; Schweder, Melani M., author; Szallar, Steve E., author; Wood, Lacey M., author; Larson, Dennis G., author; Luckasen, Gary J., author; Hickey, Matthew S., author; Bell, Christopher, author; Public Library of Science, publisher
    The conversion of white adipose to the highly thermogenic beige adipose tissue has been proposed as a potential strategy to counter the unfavorable consequences of obesity. Three regulators of this conversion have recently emerged but information regarding their control is limited, and contradictory. We present two studies examining the control of these regulators. Study 1: In 10 young men, the plasma concentrations of irisin and fibroblast growth factor 21 (FGF21) were determined prior to and during activation of the sympathetic nervous system via hypoxic gas breathing (FIO2 = 0.11). The measurements were performed twice, once with and once without prior/concurrent sympathetic inhibition via transdermal clonidine administration. FGF21 was unaffected by basal sympathetic inhibition (338±113 vs. 295±80 pg/mL; P = 0.43; mean±SE), but was increased during hypoxia mediated sympathetic activation (368±135); this response was abrogated (P = 0.035) with clonidine (269±93). Irisin was unaffected by sympathetic inhibition and/or hypoxia (P>0.21). Study 2: The plasma concentration of irisin and FGF21, and the skeletal muscle protein content of fibronectin type III domain containing 5 (FNDC5) was determined in 19 young adults prior to and following three weeks of sprint interval training (SIT). SIT decreased FGF21 (338±78 vs. 251±36; P = 0.046) but did not affect FNDC5 (P = 0.79). Irisin was decreased in males (127±18 vs. 90±23 ng/mL; P = 0.045) and increased in females (139±14 vs. 170±18). Collectively, these data suggest a potential regulatory role of acute sympathetic activation pertaining to the browning of white adipose; further, there appears to be a sexual dimorphic response of irisin to SIT.
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    Walking speed and brain glucose uptake are uncoupled in patients with multiple sclerosis
    (Colorado State University. Libraries, 2015-02-02) Kindred, John H., author; Tuulari, Jetro J., author; Bucci, Marco, author; Kalliokoski, Kari K., author; Rudroff, Thorsten, author; Frontiers Media S. A., publisher
    Motor impairments of the upper and lower extremities are common symptoms of multiple sclerosis (MS). While some peripheral effects like muscle weakness and loss of balance have been shown to influence these symptoms, central nervous system activity has not been fully elucidated. The purpose of this study was to determine if alterations in glucose uptake were associated with motor impairments in patients with multiple sclerosis. Eight patients with multiple sclerosis (4 men) and 8 sex matched healthy controls performed 15 minutes of treadmill walking at a self-selected pace, during which ≈ 322 MBq of the positron emission tomography glucose analogue [18F]-Fluorodeoxyglucose was injected. Immediately after the cessation of walking, participants underwent positron emission tomography imaging. Patients with MS had lower FDG uptake in ≈ 40% of the brain compared to the healthy controls (pFWE-corr > 0.001, qFDR-corr < 0.001, ke = 93851) and walked at a slower speed (MS, 1.1 (0.2), Controls 1.4 (0.1), m/sec, P = 0.014). Within the area of lower FDG uptake 15 regions were identified. Of these 15 regions, 13 were found to have strong to moderate correlations to walking speed within the healthy controls (r > -0.75, P < 0.032). Within patients with MS only 3 of the 15 regions showed significant correlations: insula (r = -0.74, P = 0.036), hippocampus (r = -0.72, P = 0.045), and calcarine sulcus (r = -0.77, P = 0.026). This data suggests that walking impairments in patients with MS may be due to network wide alterations in glucose metabolism. Understanding how brain activity and metabolism are altered in patients with MS may allow for better measures of disability and disease status within this clinical population.