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1. Sex differences in the association between skeletal muscle energetics and perceived physical fatigability: the Study of Muscle, Mobility and Aging (SOMMA)

Author

Gay, Emma L., Coen, Paul M., Harrison, Stephanie, Garcia, Reagan E., Qiao, Yujia (Susanna), Goodpaster, Bret H., Forman, Daniel E., Toledo, Frederico G. S., Distefano, Giovanna, Kramer, Philip A., Ramos, Sofhia V., Molina, Anthony J. A., Nicklas, Barbara J., Cummings, Steven R., Cawthon, Peggy M., Hepple, Russell T., Newman, Anne B., and Glynn, Nancy W.

Published
2024
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3. Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise

Author

Sanford, James A, Nogiec, Christopher D, Lindholm, Malene E, Adkins, Joshua N, Amar, David, Dasari, Surendra, Drugan, Jonelle K, Fernández, Facundo M, Radom-Aizik, Shlomit, Schenk, Simon, Snyder, Michael P, Tracy, Russell P, Vanderboom, Patrick, Trappe, Scott, Walsh, Martin J, Consortium, the Molecular Transducers of Physical Activity, Evans, Charles R, Fernandez, Facundo M, Li, Yafeng, Tomlinson, Lyl, Alekel, D Lee, Bekirov, Iddil, Boyce, Amanda T, Boyington, Josephine, Fleg, Jerome L, Joseph, Lyndon JO, Laughlin, Maren R, Maruvada, Padma, Morris, Stephanie A, McGowan, Joan A, Nierras, Concepcion, Pai, Vinay, Peterson, Charlotte, Ramos, Ed, Roary, Mary C, Williams, John P, Xia, Ashley, Cornell, Elaine, Rooney, Jessica, Miller, Michael E, Ambrosius, Walter T, Rushing, Scott, Stowe, Cynthia L, Rejeski, W Jack, Nicklas, Barbara J, Pahor, Marco, Lu, Ching-ju, Trappe, Todd, Chambers, Toby, Raue, Ulrika, Lester, Bridget, Bergman, Bryan C, Bessesen, David H, Jankowski, Catherine M, Kohrt, Wendy M, Melanson, Edward L, Moreau, Kerrie L, Schauer, Irene E, Schwartz, Robert S, Kraus, William E, Slentz, Cris A, Huffman, Kim M, Johnson, Johanna L, Willis, Leslie H, Kelly, Leslie, Houmard, Joseph A, Dubis, Gabriel, Broskey, Nick, Goodpaster, Bret H, Sparks, Lauren M, Coen, Paul M, Cooper, Dan M, Haddad, Fadia, Rankinen, Tuomo, Ravussin, Eric, Johannsen, Neil, Harris, Melissa, Jakicic, John M, Newman, Anne B, Forman, Daniel D, Kershaw, Erin, Rogers, Renee J, Nindl, Bradley C, Page, Lindsay C, Stefanovic-Racic, Maja, and Barr, Susan L

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Physical Activity, Prevention, Cardiovascular, Behavioral and Social Science, Generic health relevance, Good Health and Well Being, Adolescent, Adult, Animals, Child, Exercise, Female, Humans, Male, Middle Aged, Oxygen Consumption, Physical Endurance, Research Design, Young Adult, Molecular Transducers of Physical Activity Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.

Published
2020

5. Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise

Author

Adkins, Joshua N., Amar, David, Dasari, Surendra, Drugan, Jonelle K., Evans, Charles R., Fernandez, Facundo M., Li, Yafeng, Lindholm, Malene E., Nogiec, Christopher D., Radom-Aizik, Shlomit, Sanford, James A., Schenk, Simon, Snyder, Michael P., Tomlinson, Lyl, Tracy, Russell P., Trappe, Scott, Vanderboom, Patrick, Walsh, Martin J., Lee Alekel, D., Bekirov, Iddil, Boyce, Amanda T., Boyington, Josephine, Fleg, Jerome L., Joseph, Lyndon J.O., Laughlin, Maren R., Maruvada, Padma, Morris, Stephanie A., McGowan, Joan A., Nierras, Concepcion, Pai, Vinay, Peterson, Charlotte, Ramos, Ed, Roary, Mary C., Williams, John P., Xia, Ashley, Cornell, Elaine, Rooney, Jessica, Miller, Michael E., Ambrosius, Walter T., Rushing, Scott, Stowe, Cynthia L., Jack Rejeski, W., Nicklas, Barbara J., Pahor, Marco, Lu, Ching-ju, Trappe, Todd, Chambers, Toby, Raue, Ulrika, Lester, Bridget, Bergman, Bryan C., Bessesen, David H., Jankowski, Catherine M., Kohrt, Wendy M., Melanson, Edward L., Moreau, Kerrie L., Schauer, Irene E., Schwartz, Robert S., Kraus, William E., Slentz, Cris A., Huffman, Kim M., Johnson, Johanna L., Willis, Leslie H., Kelly, Leslie, Houmard, Joseph A., Dubis, Gabriel, Broskey, Nick, Goodpaster, Bret H., Sparks, Lauren M., Coen, Paul M., Cooper, Dan M., Haddad, Fadia, Rankinen, Tuomo, Ravussin, Eric, Johannsen, Neil, Harris, Melissa, Jakicic, John M., Newman, Anne B., Forman, Daniel D., Kershaw, Erin, Rogers, Renee J., Nindl, Bradley C., Page, Lindsay C., Stefanovic-Racic, Maja, Barr, Susan L., Rasmussen, Blake B., Moro, Tatiana, Paddon-Jones, Doug, Volpi, Elena, Spratt, Heidi, Musi, Nicolas, Espinoza, Sara, Patel, Darpan, Serra, Monica, Gelfond, Jonathan, Burns, Aisling, Bamman, Marcas M., Buford, Thomas W., Cutter, Gary R., Bodine, Sue C., Esser, Karyn, Farrar, Rodger P., Goodyear, Laurie J., Hirshman, Michael F., Albertson, Brent G., Qian, Wei-Jun, Piehowski, Paul, Gritsenko, Marina A., Monore, Matthew E., Petyuk, Vladislav A., McDermott, Jason E., Hansen, Joshua N., Hutchison, Chelsea, Moore, Samuel, Gaul, David A., Clish, Clary B., Avila-Pacheco, Julian, Dennis, Courtney, Kellis, Manolis, Carr, Steve, Jean-Beltran, Pierre M., Keshishian, Hasmik, Mani, D.R., Clauser, Karl, Krug, Karsten, Mundorff, Charlie, Pearce, Cadence, Ivanova, Anna A., Ortlund, Eric A., Maner-Smith, Kristal, Uppal, Karan, Zhang, Tiantian, Sealfon, Stuart C., Zaslavsky, Elena, Nair, Venugopalan, Li, SiDe, Jain, Nimisha, Ge, YongChao, Sun, Yifei, Nudelman, German, Ruf-zamojski, Frederique, Smith, Gregory, Pincas, Nhanna, Rubenstein, Aliza, Anne Amper, Mary, Seenarine, Nitish, Lappalainen, Tuuli, Lanza, Ian R., Sreekumaran Nair, K., Klaus, Katherine, Montgomery, Stephen B., Smith, Kevin S., Gay, Nicole R., Zhao, Bingqing, Hung, Chia-Jiu, Zebarjadi, Navid, Balliu, Brunilda, Fresard, Laure, Burant, Charles F., Li, Jun Z., Kachman, Maureen, Soni, Tanu, Raskind, Alexander B., Gerszten, Robert, Robbins, Jeremy, Ilkayeva, Olga, Muehlbauer, Michael J., Newgard, Christopher B., Ashley, Euan A., Wheeler, Matthew T., Jimenez-Morales, David, Raja, Archana, Dalton, Karen P., Zhen, Jimmy, Suk Kim, Young, Christle, Jeffrey W., Marwaha, Shruti, Chin, Elizabeth T., Hershman, Steven G., Hastie, Trevor, Tibshirani, Robert, Rivas, Manuel A., and Fernández, Facundo M.

Published
2020
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6. Relationships between mitochondrial content and bioenergetics with obesity, body composition and fat distribution in healthy older adults

Author

Bharadwaj, Manish S, Tyrrell, Daniel J, Leng, Iris, Demons, Jamehl L, Lyles, Mary F, Carr, J Jeffrey, Nicklas, Barbara J, and Molina, Anthony JA

Subjects
Health Sciences, Sports Science and Exercise, Aging, Nutrition, Prevention, Clinical Research, Diabetes, Obesity, Metabolic and endocrine, Adiposity, Mitochondria, Muscle, Health services and systems, Public health
Abstract

BackgroundMitochondrial function declines with age; however, the relationship between adiposity and mitochondrial function among older adults is unclear. This study examined relationships between skeletal muscle mitochondrial content and electron transport chain complex 2 driven respiration with whole body and thigh composition, body fat distribution, and insulin sensitivity in older adults.Methods25 healthy, sedentary, weight-stable men (N = 13) and women (N = 12) >65 years of age, with a BMI range of 18-35 kg/m(2), participated in this study. Vastus lateralis biopsies were analyzed for citrate synthase (CS) activity and succinate mediated respiration of isolated mitochondria. Whole body and thigh composition were measured by DXA and CT. HOMA-IR was calculated using fasting glucose and insulin as an estimate of insulin sensitivity.ResultsSimilar to reports in middle-aged adults, skeletal muscle CS activity was negatively correlated with BMI (R = -0.43) in our cohort of older adults. Higher total and thigh adiposity were correlated with lower CS activity independent of BMI (R = -0.50 and -0.71 respectively). Maximal complex 2 driven mitochondrial respiration was negatively correlated with lower body adiposity in males (R = -0.66). In this cohort of non-diabetic older adults, both HOMA-IR and insulin were positively correlated with CS activity when controlling for BMI (R = 0.57 and 0.66 respectively).ConclusionsAdiposity and body composition are correlated with skeletal muscle mitochondrial content and electron transport chain function in healthy, sedentary, community dwelling, older adults. Specific relationships of mitochondrial bioenergetics with gender and insulin sensitivity are also apparent.Trial registrationClinicalTrials.gov identifier NCT01049698.

Published
2015

7. Alterations of a Cellular Cholesterol Metabolism Network Are a Molecular Feature of Obesity-Related Type 2 Diabetes and Cardiovascular Disease

Author

Ding, Jingzhong, Reynolds, Lindsay M, Zeller, Tanja, Müller, Christian, Lohman, Kurt, Nicklas, Barbara J, Kritchevsky, Stephen B, Huang, Zhiqing, de la Fuente, Alberto, Soranzo, Nicola, Settlage, Robert E, Chuang, Chia-Chi, Howard, Timothy, Xu, Ning, Goodarzi, Mark O, Chen, Y-D Ida, Rotter, Jerome I, Siscovick, David S, Parks, John S, Murphy, Susan, Jacobs, David R, Post, Wendy, Tracy, Russell P, Wild, Philipp S, Blankenberg, Stefan, Hoeschele, Ina, Herrington, David, McCall, Charles E, and Liu, Yongmei

Subjects
Biomedical and Clinical Sciences, Heart Disease, Genetics, Atherosclerosis, Cardiovascular, Human Genome, Heart Disease - Coronary Heart Disease, Nutrition, Diabetes, Prevention, Obesity, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Good Health and Well Being, Aged, Aged, 80 and over, Cardiovascular Diseases, Cholesterol, Delta-5 Fatty Acid Desaturase, Diabetes Mellitus, Type 2, Female, Gene Dosage, Gene Expression Regulation, Humans, Male, Transcriptome, Weight Loss, Inflammation, Coronary artery calcification, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

Obesity is linked to type 2 diabetes (T2D) and cardiovascular diseases; however, the underlying molecular mechanisms remain unclear. We aimed to identify obesity-associated molecular features that may contribute to obesity-related diseases. Using circulating monocytes from 1,264 Multi-Ethnic Study of Atherosclerosis (MESA) participants, we quantified the transcriptome and epigenome. We discovered that alterations in a network of coexpressed cholesterol metabolism genes are a signature feature of obesity and inflammatory stress. This network included 11 BMI-associated genes related to sterol uptake (↑LDLR, ↓MYLIP), synthesis (↑SCD, FADS1, HMGCS1, FDFT1, SQLE, CYP51A1, SC4MOL), and efflux (↓ABCA1, ABCG1), producing a molecular profile expected to increase intracellular cholesterol. Importantly, these alterations were associated with T2D and coronary artery calcium (CAC), independent from cardiometabolic factors, including serum lipid profiles. This network mediated the associations between obesity and T2D/CAC. Several genes in the network harbored C-phosphorus-G dinucleotides (e.g., ABCG1/cg06500161), which overlapped Encyclopedia of DNA Elements (ENCODE)-annotated regulatory regions and had methylation profiles that mediated the associations between BMI/inflammation and expression of their cognate genes. Taken together with several lines of previous experimental evidence, these data suggest that alterations of the cholesterol metabolism gene network represent a molecular link between obesity/inflammation and T2D/CAC.

Published
2015

8. Associations between skeletal muscle energetics and accelerometry‐based performance fatigability: Study of Muscle, Mobility and Aging.

Author

Qiao, Yujia, Santanasto, Adam J., Coen, Paul M., Cawthon, Peggy M., Cummings, Steven R., Forman, Daniel E., Goodpaster, Bret H., Harezlak, Jaroslaw, Hawkins, Marquis, Kritchevsky, Stephen B., Nicklas, Barbara J., Toledo, Frederico G. S., Toto, Pamela E., Newman, Anne B., and Glynn, Nancy W.

Subjects
WRIST, SKELETAL muscle, NUCLEAR magnetic resonance spectroscopy, AGING, OLDER people, PERFORMANCE theory
Abstract

Performance fatigability is typically experienced as insufficient energy to complete daily physical tasks, particularly with advancing age, often progressing toward dependency. Thus, understanding the etiology of performance fatigability, especially cellular‐level biological mechanisms, may help to delay the onset of mobility disability. We hypothesized that skeletal muscle energetics may be important contributors to performance fatigability. Participants in the Study of Muscle, Mobility and Aging completed a usual‐paced 400‐m walk wearing a wrist‐worn ActiGraph GT9X to derive the Pittsburgh Performance Fatigability Index (PPFI, higher scores = more severe fatigability) that quantifies percent decline in individual cadence‐versus‐time trajectory from their maximal cadence. Complex I&II‐supported maximal oxidative phosphorylation (max OXPHOS) and complex I&II‐supported electron transfer system (max ETS) were quantified ex vivo using high‐resolution respirometry in permeabilized fiber bundles from vastus lateralis muscle biopsies. Maximal adenosine triphosphate production (ATPmax) was assessed in vivo by 31P magnetic resonance spectroscopy. We conducted tobit regressions to examine associations of max OXPHOS, max ETS, and ATPmax with PPFI, adjusting for technician/site, demographic characteristics, and total activity count over 7‐day free‐living among older adults (N = 795, 70–94 years, 58% women) with complete PPFI scores and ≥1 energetics measure. Median PPFI score was 1.4% [25th–75th percentile: 0%–2.9%]. After full adjustment, each 1 standard deviation lower max OXPHOS, max ETS, and ATPmax were associated with 0.55 (95% CI: 0.26–0.84), 0.39 (95% CI: 0.09–0.70), and 0.54 (95% CI: 0.27–0.81) higher PPFI score, respectively. Our findings suggested that therapeutics targeting muscle energetics may potentially mitigate fatigability and lessen susceptibility to disability among older adults. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Associations between skeletal muscle energetics and accelerometry‐based performance fatigability: Study of Muscle, Mobility and Aging

Author

Qiao, Yujia (Susanna), primary, Santanasto, Adam J., additional, Coen, Paul M., additional, Cawthon, Peggy M., additional, Cummings, Steven R., additional, Forman, Daniel E., additional, Goodpaster, Bret H., additional, Harezlak, Jaroslaw, additional, Hawkins, Marquis, additional, Kritchevsky, Stephen B., additional, Nicklas, Barbara J., additional, Toledo, Frederico G. S., additional, Toto, Pamela E., additional, Newman, Anne B., additional, and Glynn, Nancy W., additional

Published
2023
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17. A Randomized, Controlled Trial of Resistance Training Added to Caloric Restriction Plus Aerobic Exercise Training in Obese Heart Failure with Preserved Ejection Fraction

Author

Brubaker, Peter H., primary, Nicklas, Barbara J., additional, Houston, Denise K., additional, Hundley, W. Gregory, additional, Chen, Haiying, additional, Molina, M. Anthony J. A., additional, Lyles, W. Mary, additional, Nelson, Benjamin, additional, Upadhya, Bharathi, additional, Newland, Russell, additional, and Kitzman, Dalane W., additional

Published
2022
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28. Changes in Body Weight and Knee Pain in Adults With Knee Osteoarthritis Three‐and‐a‐Half Years After Completing Diet and Exercise Interventions: Follow‐Up Study for a Single‐Blind, Single‐Center, Randomized Controlled Trial

Author

Messier, Stephen P., primary, Newman, Jovita J., additional, Scarlett, Matthew J., additional, Mihalko, Shannon L., additional, Miller, Gary D., additional, Nicklas, Barbara J., additional, DeVita, Paul, additional, Hunter, David J., additional, Lyles, Mary F., additional, Eckstein, Felix, additional, Guermazi, Ali, additional, Loeser, Richard F., additional, and Beavers, Daniel P., additional

Published
2022
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38. Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications

Author

Yang, Rong-Ze, Lee, Mi-Jeong, Hu, Hong, Pollin, Tonni I., Ryan, Alice S., Nicklas, Barbara J., Snitker, Soren, Horenstein, Richard B., Hull, Kristen, Goldberg, Nelson H., Goldberg, Andrew P., Shuldiner, Alan R., Fried, Susan K., and Gong, Da-Wei

Subjects
Metabolic diseases, Cardiovascular diseases, Obesity, Inflammation
Abstract

ABSTRACT Background Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD). However, the molecular and cellular mechanisms that link [...]

Published
2006

48. Effect of Exercise Type during Intentional Weight Loss on Body Composition in Older Adults with Obesity

Author

Beavers, Kristen M., Ambrosius, Walter T., Rejeski, W. Jack, Burdette, Jonathan H., Walkup, Michael P., Sheedy, Jessica L., Nesbit, Beverly A., Gaukstern, Jill E., Nicklas, Barbara J., and Marsh, Anthony P.

Subjects
Male, body composition, aerobic exercise, resistance exercise, Weight Loss, aging, Humans, Female, Obesity, Exercise, Article, mobility, Aged
Abstract

Objective To examine the long-term effects of exercise modality during weight loss on body composition and associations between body composition and physical function changes. Methods 249 older adults (66.9±4.7 years, 71% women, 32% African American, BMI: 34.4±3.7 kg/m2) were randomized to weight loss (WL; n=82), WL plus aerobic training (WL+AT; n=86), or WL plus resistance training (WL+RT; n=81) for 18-months. DXA-acquired body composition, 400-m walk time, and knee extensor strength were measured at baseline, 6-, and 18-months. Results Total body mass loss was enhanced when WL was combined with exercise (WL: −5.7±0.7 kg, WL+AT: −8.5±0.7 kg, WL+RT: −8.7±0.7 kg; p

Published
2017

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