Resistance Training Modulation of Fat Metabolism in Obese Postmenopausal Women - 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.
