Regional Fatty Acid Metabolism In Humans

Project Summary/Abstract Our goal is to understand the why obesity, and specifically upper body/visceral obesity (UBO), causes insulin resistance, Type 2 Diabetes and the other health problems. We study what regulates the storage of fat in adipose tissue and release of free fatty acids (FFA) from adipose tissue (lipolysis) in humans. For this application we propose to complete five Specific Aims. We will determine whether, in response to an energy deficit intervention that results in an 8 kg loss of body fat in adults with Class I obesity: 1) preferential upper body/visceral fat loss will be associated with greater improvements in metabolic health; 2); basal/meal suppressed lipolysis in UBSQ and LBSQ adipose tissue under baseline and/or active weight-loss conditions is related to preferential loss of fat from those depots; 3) meal fat storage in UBSQ and LBSQ adipose tissue under baseline and/or active weight-loss conditions is related to preferential loss of fat from those depots; 4) the functional (enzyme) and gene regulation responses in UBSQ and LBSQ adipose tissue predicts changes in fat storage/release; 5) the depot-specific fat loss will be similar in pre- and postmenopausal women. These studies will offer insights as to whether inter-individual differences in adipose tissue lipolysis or meal fatty acid storage in adipose tissue are responsible for differential fat loss from lower body and upper body fat. The responses of different adipose tissue depots to weight loss interventions will provide mechanistic information as part of our goals of identifying obesity phenotypes that can inform future therapeutic strategies to maximize the health benefits of weight loss.