Endocrine and paracrine negative regulators of adipose differentiation.

Obesity which is characterized by an abnormal adipose tissue development is a first degree public health hazard in industrialized countries. One important aspect in the study of adipose tissue development is to investigate the hormonal control of proliferation and differentiation. Any qualitative or quantitative change in these hormones or their receptors can result in abnormalities in the process of proliferation and/or differentiation possibly leading to obesity. Therefore, it is important to identify these factors and investigate their mechanism of action. We have concentrated our efforts in the study of factors triggering differentiation (positive regulators) and also of factors inhibiting differentiation (negative regulators). The present paper provides evidence of the importance of EGF/TGF-alpha and of PGF2 alpha as differentiation inhibitors for adipocyte precursors in primary culture. Data presented here also demonstrate that TGF-alpha is expressed in adipose tissue and that its expression is specifically stimulated by PGF2 alpha, thus suggesting the existence of an amplification mechanism between two differentiation inhibitors within the adipose tissue. The importance of these two types of differentiation inhibitors in the regulation of adipose tissue development is discussed.