Grant: Project Grant

Excess accumulation of fat inside the abdomen, termed visceral obesity, is generally predominant in men but it is also found in women. The presence of those large visceral fat stores has been closely linked to metabolic abnormalities which lead to diabetes and heart disease. Would it be possible to reduce fat storage in adipose tissue located inside the abdominal cavity and favor accumulation of fat tissues located under the skin, or subcutaneous fat? If so, this could delay the onset of diseases in individuals with abdominal obesity. Our main postulate is that this can be done by changing the amount of hormone dihydrotestosterone specifically in visceral fat. We have evidence that adipose tissues can generate a portion of their own dihydrotestosterone from other hormones such as adrenal androgen precursors or testosterone and also inactivate this hormone. We wish to prove that blocking the enzyme responsible for dihydrotestosterone inactivation will change the availability of the hormone in each fat compartment and will direct excess dietary lipids away from the visceral fat stores. To reach this goal, we will use cultures of adipose cells or explants obtained from various fat compartments in men and women. We will prove that the enzyme involved in dihydrotestosterone inactivation plays a significant role in the modulation of fat distribution patterns in humans by studying its impact on adipose tissue, its hormonal regulation and its genetic variation. We postulate that studying androgen inactivation in fat will contribute to identify new targets for the remodeling of adipose tissue distribution in humans.