The adipose tissue is playing an important role in the development of human obesity and its related comorbidities, but little is known about the mechanisms governing its differentiation and proliferation. In this work, we studied the expression of transcription factors involved in fat storage and metabolic regulations in adipose tissue of 50 well-characterized obese women. In multivariate analyses, 80% of c enhancer binding protein alpha (cEBPalpha), c and a sterol regulatory element binding protein 1 (c and a SREBP1), and retinoid X receptor (RXRalpha) levels in sc adipose tissue (SAT) could be explained by other transcription factors. In addition, RXRalpha was the major determinant of peroxisome proliferator and activated receptor-gamma1 variability in SAT, with the two factors being involved in the determination of the variability of insulin resistance. In contrast, the levels of all these transcription factors, together with various phenotypic and biological characteristics of the patients, seemed to participate only marginally in the regulation of visceral adipose tissue activity. In similar multivariate analyses, they could explain only a minor part of the variability of cEBPalpha, c and a SREBP1, or RXRalpha, suggesting the involvement of other regulators. Overall, our results demonstrate a different regulation of visceral adipose tissue and SAT and a different role of both tissues in insulin resistance and lipid storage.