Neurosteroid Regulation of Adiposity, Glucose Homeostasis and Energy Expenditure in Primates
Sponsor: NIH AAH3686 PI: J Levine, PhD
We will use both pharmacological and viral vectormediated shRNA approaches to determine if adiposity, glucoregulation and energy metabolism are altered by inhibition of the CYP19A1 aromatase enzyme, or by permanent silencing of the CYP19A1 gene in the hypothalamus of female rhesus macaques. We will also analyze the synthesis of E2 in the VMN and ARC by a microdialysis approach, and determine whether VMN and ARC E2 originates from hypothalamically synthesized androgens. These studies may fundamentally change our understanding of metabolic control of adiposity, glucoregulation and energy homeostasis by sex steroids in female NHPs, and prompt exploration of new therapeutic strategies to diminish metabolic disease in women.