Project Summary
Prediabetes, a comorbidity of obesity and a precursor of type 2 diabetes, affects more than one-half of women over
60 years of age. Obesity has multiple causes; however, it is known that obese insulin resistant individuals have a
reduced ability to alter resting and stimulated lipolysis (fat breakdown). This lack of flexibility to respond to stimuli
that regulate lipolysis has been attributed, almost entirely through studies in males, to changes in the predominant
(catecholamine-mediated) lipolytic pathway. Our published preliminary data demonstrate that acute resistance
exercise increases lipolysis in non-obese women. Published data also indicate that resistance exercise, like
endurance exercise, increases lipolytic sensitivity in men. However, the alterations in lipolytic response due to
resistance, as compared to endurance, training matched for energy expenditure have not been investigated. It is
also unknown how training alters lipolysis during general physical activity (walking), which accounts for the majority
of activity people engage in during a typical day outside of planned exercise. Furthermore, the lack of prior
investigations in this area in women points to the need for resistance training studies of fat metabolism in women
to determine if resistance training is as effective as endurance training. Therefore, the overall objective of this
study is to compare the effects of 12 weeks of resistance training to endurance training with respect to fat
metabolism, with a focus on lipolysis in postmenopausal women with obesity and prediabetes. Our central
hypothesis is that both 12 weeks of resistance training and 12 weeks of endurance training will increase lipolytic
flexibility. We will compare the effects of endurance training to the effects imparted by calorie-matched endurance
exercise training. We will determine with powerful in-vivo microdialysis and stable isotope methodologies the extent
to which 12 weeks of resistance training, as compared to calorie-matched endurance training: a) increases physical
activity (walking)-stimulated whole-body and regional lipolysis (Aim 1); b) increases local adrenergic regulation of
lipolysis in subcutaneous abdominal and gluteal adipose tissue (Aim 2); and c) increases insulin-mediated
suppression of whole-body and regional lipolysis (Aim 3) in postmenopausal women with obesity and prediabetes.
Secondarily, fat oxidation, lipogenesis and adipogenesis in adipose tissue, as well as lipolytic activity in skeletal
muscle, will also be studied to develop a global understanding of fat metabolism response to resistance exercise
training. In addition, we will investigate the influence of resistance and endurance training on glucose profile under
laboratory as well as free-living conditions, as poor glucose control is linked to the aberrant lipid metabolism
commonly associated with obesity. These studies will provide a greater understanding of how these exercise
modalities affect metabolism in women with obesity and prediabetes, allowing practitioners to make more evidence-
based exercise prescriptions intended to improve body composition, glycemic control, and weight management.