This study will determine the effects of 6 mo. of dietary-induced weight loss (WL) with and without low-intensity endurance exercise (EX) on: 1) cellular mechanisms regulating abdominal and gluteal subcutaneous adipocyte lipolysis; 2) circulating concentrations of hormones known to modulate adipocyte lipolysis, fat oxidation and resting metabolic rate (RMR); and 3) regional fat distribution (intra-abdominal fat area and waist-to-hip ratio) and changes in risk factors (lipoprotein lipids, glucose tolerance and insulin) for cardiovascular disease (CVD) in obese, postmenopausal women. The hypothesis is that the addition of EX to a WL program will prevent the decline in adipocyte lipolysis related to an increased alpha-2-adrenergic receptor (AR) sensitivity and decreased hormone sensitive lipase (HSL) after WL by increasing beta-AR sensitivity and HSL expression, thus maintaining rates of fat oxidation and RMR in weight-reduced postmenopausal women. Furthermore, WL with EX will lead to a preferential loss of fat from the abdominal region and greater improvements in metabolic risk factors for CVD compared to WL without EX. After random assignment to WL or WL+EX, obese (25-35 kg/m2) women, 1-10 yr. past menopause (50-60 yr.) who are healthy, sedentary, non-smoking, and not on estrogen replacement will undergo WL therapy consisting of a hypocaloric diet for 6 months. The WL+EX group will walk 3 d/wk for 45 min. at a target HR that corresponds to 50%-70% of maximal aerobic capacity. Research testing will occur after an initial 6-wk dietary stabilization period, post-WL after a 2-wk weight stabilization period, and after a 12-mo. weight maintenance follow-up. Cellular mechanisms regulating lipolytic responsiveness and sensitivity will be determined by measuring glycerol release from intact adipocytes in the presence of receptor- and post-receptor-and post-receptor agonists, by assessing beta- and alpha-2-AR affinity and density, and by measuring expression of HSL. The intent is to provide new information regarding the mechanisms by which the addition of endurance EX during caloric restriction prevents or blunts reductions in adipocyte lipolysis, and whether alterations in lipolysis with WL and WL+EX are associated with changes in fat oxidation, RMR, body fat distribution and risk factors for CVD. The results will also determine whether metabolic alterations seen with WL and WL+EX are associated with the amount of weight loss during treatment and weight gain during follow-up. The findings will have important clinical implications for the development of successful WL treatments that reduce abdominal obesity and risk factors for CVD in obese, postmenopausal women.

R29AG014066

1996-09-30

2003-03-31