Coordinated adipogenesis helps maintain adipose tissue function and reduce obesity-associated complications including type 2 diabetes. We previously demonstrated that FGF-1 promotes adipogenesis via a novel BAMBI/PPARg-dependent pathway. Here, we employed a combination of RNA-Seq, functional investigations and association studies to identify novel downstream regulators of adipogenesis implicated in the modulation of local and systemic insulin sensitivity. FGF-1 altered the expression of 598 genes, including 49 ‘interferome’ genes, of which 11 were downstream of BAMBI and PPARg. In silico analysis of known and predicted protein-protein interactions revealed a nexus that included all 11 FGF-1/BAMBI/PPARg-dependent genes. Functional characterization of five nexus genes revealed all were negative regulators of adipogenesis. Determination of the expression profile of the nexus genes in subcutaneous human adipose tissue from a cohort of obese males with varying degrees of insulin sensitivity showed expression of all five nexus genes correlated with local (adipose) and systemic (skeletal muscle) insulin sensitivity. This contrasted with a classic inflammatory gene signature which showed the expected inverse correlation with insulin sensitivity. Moreover, in a cohort of subjects without overt metabolic dysfunction expression of both interferome nexus genes and inflammatory genes showed a positive correlation with BMI. Collectively these findings increase our understanding of the molecular networks that regulate adipogenesis and, somewhat paradoxically, reveal the interferome nexus as a potential positive regulator of both local and systemic insulin sensitivity. Further studies are warranted to explore the molecular mechanisms and define potential therapeutic opportunities.