There is conclusive evidence that excess fat mass, independent of muscle mass, is a risk factor for physical function decline with aging. While, chronic resistance exercise improves functional ability in normal-weight older adults, obese individuals may not experience the same magnitude of benefit from a given exercise stimulus. Since specific inflammatory factors secreted by adipose tissue have direct effects on skeletal muscle morphologic and metabolic properties, it is likely that addition of caloric restriction resulting in loss of body fat to a resistance exercise intervention will be more efficacious for enhancing functional adaptations than exercise alone in obese elderly, a population at a particularly high risk for disability. This study is a randomized, clinical trial in 130 older (65-79 yrs), obese (BMI=30-34.9 kg/m2), sedentary women and men with low physical function designed to determine whether addition of caloric restriction (CR) to a standardized, progressive resistance training (RT) program enhances improvements in skeletal muscle and overall physical function. We will also examine the effects of the two interventions on in vitro characteristics of skeletal muscle and on systemic and abdominal adipose tissue levels of inflammation. Subjects will be randomized to 5 months of RT alone (RT) or RT with caloric restriction (RT+CR;-600 kcal/day deficit) designed to elicit considerable loss of body fat (<8.7 kg fat loss).
The Specific Aims are to determine the effect of adding CR to RT on: 1) clinical measures of skeletal muscle function and overall physical function;2) in vitro characteristics of skeletal muscle (single-fiber contractile force and power, intramyocellular lipid, and muscle gene and protein expression of interleukin-6 and tumor necrosis factor alpha);and 3) inflammatory activity of abdominal adipose tissue and circulating adipokines. Our primary hypothesis is: Compared to RT only, RT+CR will result in greater improvement in muscle function, assessed by knee extensor force per unit of muscle tissue (muscle quality) and leg press muscle power, and in overall physical function, assessed by Short Physical Performance Battery (SPPB) score. Confirmation of this hypothesis will provide persuasive evidence that addition of CR to a RT intervention in older, obese women and men may be a more effective treatment than RT alone for prevention or delay of disability.

Public Health Relevance

This study will determine whether older, obese men and women who lose weight by dieting during a weight lifting program will experience greater improvements in muscle strength and physical function as a result of their exercise efforts. The results will also provide information on the effects of dieting during an exercise program on specific biological factors, including single muscle fiber strength, fat storage within muscle fibers, and inflammation in muscle and fat tissue.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG020583-10
Application #
8466267
Study Section
Aging Systems and Geriatrics Study Section (ASG)
Program Officer
Joseph, Lyndon
Project Start
2002-07-01
Project End
2014-06-30
Budget Start
2013-09-15
Budget End
2014-06-30
Support Year
10
Fiscal Year
2013
Total Cost
$294,929
Indirect Cost
$88,192
Name
Wake Forest University Health Sciences
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Choi, Seung J; Files, D Clark; Zhang, Tan et al. (2016) Intramyocellular Lipid and Impaired Myofiber Contraction in Normal Weight and Obese Older Adults. J Gerontol A Biol Sci Med Sci 71:557-64
Normandin, Eve; Chmelo, Elizabeth; Lyles, Mary F et al. (2016) Effect of Resistance Training and Caloric Restriction on the Metabolic Syndrome. Med Sci Sports Exerc :
Molina, Anthony J A; Bharadwaj, Manish S; Van Horn, Cynthia et al. (2016) Skeletal Muscle Mitochondrial Content, Oxidative Capacity, and Mfn2 Expression Are Reduced in Older Patients With Heart Failure and Preserved Ejection Fraction and Are Related to Exercise Intolerance. JACC Heart Fail 4:636-45
Kitzman, Dalane W; Brubaker, Peter; Morgan, Timothy et al. (2016) Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial. JAMA 315:36-46
Chmelo, E A; Beavers, D P; Lyles, M F et al. (2016) Legacy effects of short-term intentional weight loss on total body and thigh composition in overweight and obese older adults. Nutr Diabetes 6:e203
Messi, María Laura; Li, Tao; Wang, Zhong-Min et al. (2016) Resistance Training Enhances Skeletal Muscle Innervation Without Modifying the Number of Satellite Cells or their Myofiber Association in Obese Older Adults. J Gerontol A Biol Sci Med Sci 71:1273-80
Sergeant, Susan; Ruczinski, Ingo; Ivester, Priscilla et al. (2016) Impact of methods used to express levels of circulating fatty acids on the degree and direction of associations with blood lipids in humans. Br J Nutr 115:251-61
Jefferson, Margie E; Nicklas, Barbara J; Chmelo, Elizabeth A et al. (2016) Effects of Resistance Training With and Without Caloric Restriction on Arterial Stiffness in Overweight and Obese Older Adults. Am J Hypertens 29:494-500
Wang, Xuewen; You, Tongjian; Murphy, Karin et al. (2015) Addition of Exercise Increases Plasma Adiponectin and Release from Adipose Tissue. Med Sci Sports Exerc 47:2450-5
Zhang, Tan; Birbrair, Alexander; Wang, Zhong-Min et al. (2015) Improved knee extensor strength with resistance training associates with muscle specific miRNAs in older adults. Exp Gerontol 62:7-13

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