Loss of Fat Tissue and Functional Responses to Exercise in Older, Obese Adults (I’M FIT)

Contact: Barbara Nicklas, PhD

There is conclusive evidence that excess fat mass, independent of muscle mass, is a risk factor for physical function decline with aging.  While regular exercise, especially resistance exercise, improves functional ability in older adults, not all individuals 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, there may be effects of fat loss per se on functional adaptations to exercise training. 

This study is a randomized, clinical trial in 120 older (65-79 yrs), obese (BMI=30-34.9 kg/m2), sedentary women and men with low physical function designed to determine whether a concurrent loss of body fat via caloric restriction enhances improvements in skeletal muscle and physical function in response to a 5-month standardized, progressive resistance training (RT) program.  We will also begin to explore potential mechanisms by which fat loss may affect muscle adaptations to RT.  Subjects will be randomized to RT alone (RT) or RT with caloric restriction (RT+Fat Loss) intended to elicit substantial fat loss (-600 kcal/d deficit; ~8.7 kg fat loss). 

The Specific Aimsare to determine the effect of concurrent loss of body fat on: 1) clinical measures of skeletal muscle function and overall physical function, 2) in vitro characteristics of skeletal muscle, and 3) inflammatory activity of abdominal adipose tissue and circulating adipokines, in response to the exercise intervention.  As a first step in identifying potential mechanisms for an additive effect of fat loss on muscle adaptations to RT, we will also assess whether improvements in the functional outcomes are associated with changes in in vitro characteristics of skeletal muscle (intra-myocellular lipid, single-fiber contractile force/power, and gene expression of IL-6 and TNF_), as well as with systemic and adipose tissue indicators of inflammation (gene expression and release of adiponectin, IL-6 and TNFa, and macrophage cell number).  Our primary hypothesis is: Compared to the RT only group, the RT+Fat Loss group will show greater improvement in muscle function, assessed by knee extensor force per unit of muscle tissue (muscle quality) and leg press muscle power, and physical function, assessed by Short Physical Performance Battery score.   

Confirmation of our hypotheses will provide persuasive evidence, and initial mechanistic insight, that addition of caloric restriction (for fat loss) to a resistance training intervention in older, obese women and men may be a more effective treatment than exercise alone for prevention or delay of disability in the obese, elderly person.