Cellular and Molecular Aspects of the Regulation of Adipogenesis1

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Abstract
Understanding the regulation of adipogenesis dictates consideration of the type of system studied. Numerous in vitro studies involve preadipocyte cell lines or stromal-vascular (S-V) cells from adipose tissue. Fundamental characteristics and direction and degree of response to major hormones clearly distinguish preadipocytes from S-V cells. The concept of “endocrine imprinting” may partially resolve apparent discrepancies between hormone requirements of S-V and preadipocyte cultures. Regardless, glucocorticoids and insulin may play a fundamental role in adipogenesis, whereas growth hormone (GH) either antagonizes adipogenesis or has no influence. A variety of evidence indicates that insulin-like growth factor I (IGF-I), prostaglandins, and transforming growth factor-beta (TGF-β) may be autocrine/paracrine factors involved in adipogenesis. The gene product (AP27) of a cDNA clone may act in an autocrine/paracrine manner by triggering adipogenesis after reaching a critical concentration. Sequence-specific DNA binding proteins are involved in control of adipogenesis at the level of gene transcription. In particular, the DNA binding protein C/EBP may be necessary and sufficient to induce adipogenesis, as evidenced by transfection studies. A number of differentiation markers have been cloned and studied in preadipocyte cultures. Markers of early and late stages of differentiation have been identified, and one early marker (pOb24) proved effective at identifying preadipocytes in vivo. Several monoclonal antibodies raised against surface antigens effectively identify preadipocytes prior to lipid deposition in vivo and in vitro. Coupling flow cytometric analysis with monoclonal antibodies provides an analytical approach to studying preadipocytes. The regulation of adipocyte development in the porcine fetus has been studied at the cellular and tissue level. The temporal pattern and type of hormone responsiveness during a sensitive period of development is hormone-dependent. Cytochemical analysis indicates a marked enhancement of adipocyte differentiation in fetal endocrine studies despite impaired differentiation of the adipocyte-associated vasculature. Therefore, complete understanding of adipose tissue regulation will ultimately depend on studies at the cell and tissue level.

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