Research: Older women accumulate fat in the upper body and this pattern of fat distribution is associated with a heightened risk of cardiovascular disease (CVD). The mechanisms regulating the metabolic consequences of abdominal (ABD) obesity and their ability to be modified by WL are not known. The hypothesis is that in postmenopausal obese women increased visceral adiposity is associated with increased lipolytic responses due to alterations in the signaling properties of the AdC-linked adrenergic receptor (AR) in ABD and gluteal (GLT) adipocytes which will be reversed by WL-induced decrease in visceral fat. Post WL AR regulation of lipolysis and reduced visceral fat will be associated with improvements in glucose and lipid metabolic CVD risk factors. The regional regulation of the stimulatory and inhibitory pathways of AdC-linked AR will be determined by measuring AR number and binding affinity of total beta and alpha2-AR, as well as proportion, density and affinity of high (beta2 and alpha2h) and low (beta1 and alpha21) affinity beta- and alpha2-AR in ABD and GLT adipocytes, modulation of cAMP synthesis (cAMP generated in crude plasma membranes detected with a radioimmunoassay), and expression of G-proteins in membranes (immunoblotting). This regulation will be compared in ABD and GLT adipocytes of postmenopausal women with increased visceral obesity before and after WL. Our results will provide new insight into the mechanisms underlying upper body obesity, and the use of WL treatment as a potential intervention to attenuate the abnormalities in adipose tissue metabolism and thus reduce the high risk of CVD, the number one cause of morbidity and mortality in postmenopausal women.
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