Regulation of gene expression by fatty acids in the adipose cell

Abstract

pocyte. The characterization of extracellular effecters and that of intracellular signals controling adipose cell differentiation has been made feasible by establishing serum-free, chemically-defined culture media (l-5). In SF medium (4.5) containing transfetrin, fetuin, growth hormone (GH), triiodothyronine (T,) and either insulin at supraphysiological concentrations or a mixture of insulin-like growth factor-I (IGF-I) and insulin at low concentrations (6). mouse Ob177 1 cells were able to express early markers of adipose conversion such as lipoprotein lipase and pOb 24 mRNA (7, 8). In order to divide at least once. and subsequently express late markers defining terminal differentiation such as glycerol-3-phosphate dehydrogenase (GPDH) activity and triacylglycerol accumulation. preadipocytes had to be exposed to 5F medium supplemented with some additional mitogenicadipogenic stimuli. Arachidonic acid (AA) was among the first mitogenic-adipogenic agent to be described (4). Stable analogues of prostacyclin (PGI,), such as carbaprostacyclin (cPGI?), as well as glucocorticoids which were able to increase AA disposal and PGI, production. were subsequently shown to substitute for AA (5. Y, IO). Detailed studies have shown that AA was acting by means of two of its metabolites: namely PGl2 and PGF,, which, in an autocrine/paracrine manner, activate adenylate cyclase and phosphatidyl inositol phospholipase C. respectively (4J.9). Activation of the CAMP/ protein kinase A pathway by PGI, appears essential to trigger terminal differentiation, whereas activation of the diacylglycerol/protein kinase C pathway by PGF,, appears only modulatory (4. 5). Altogether, the above results indicate that AA is able to control indirectly adipose cell differentiation and the expression of genes encoding for late markers by means of two of its major metabolites. More recently, however. a more direct regulation of gene expression by fatty acids (FA) was demonstrated, namely in the case of the ‘adipocyte lipid binding protein’ (ALBP or aP2) gene. Long-chain FA (C12, saturated or unsaturated) are able to activate the ALBP gene at a transcriptional level and subsequently to modulate its expression. The process of activation by FA. rather than the expression of aP2 gene. appears unique to adipose cells (11, 12). The activation of the ALBP gene takes place in the presence of nonmetabolized long-chain FA (13). It is hypothesized that FA trigger. in a rapid and fully reversible manner. the synthesis of trans-acting factor(s) at a transcriptional or translational level which, in turn, regulate the transcription of the ALBP gene.