Abstract
The regulation of the expression of adipose-related genes, i.e., aP2, adipsin, and glycerophosphate dehydrogenase (GPDH) by growth hormone (GH) and polyamines, as well as the role of fatty acids, have been investigated in polyamine-dependent Ob1754 cells and Ob1771 preadipose cells. Growth hormone acts as an obligatory hormone for adipsin and GPDH gene expression but its presence is not required for the expression of the aP2 gene. In fully differentiated Ob1771 cells, impairment of fatty acid synthesis by glucose deprivation leads to an inhibition of the aP2 gene expression, whereas the expression of adipsin and GPDH genes remains unaffected. Supplementation of the culture medium with fatty acids prevents the decrease of aP2 gene expression, and this effect appears primarily due to an increase in the transcriptional level of aP2 gene. The induction of aP2 gene has been examined in early committed, lipid-free Ob1771 cells in which fatty acid synthesis is very low despite glucose supplementation. Long-chain fatty acids (greater than or equal to C12) are able to activate the aP2 gene. It is concluded that fatty acids or fatty acid metabolites activate the aP2 gene and subsequently modulate its expression.
Highlights
The regulation of the expression of adipose-related genes, i.e., aP2, adipsin, and glycerophosphate dehydrogenase (GPDH) by growth hormone (GH) and polyamines, as well as the role of fatty acids, have been investigated in polyaminedependent Ob1754 cells and Ob1771 preadipose cells
The results of the studies performed with Ob1754 cells, a variant of Ob17 clonal line requiring putrescine supplementation for terminal differentiation[12], suggest the existence of a tight correlation between fatty acid supply, from endogenous or exogenous source, and the regulation of the expression of aP2 gene (Fig. 2)
In order to extend these observations to cells of the parental Ob17 clonal line, fully differentiated Ob1771 cells were maintained in glucose-free culture medium under conditions where RNA and protein synthesis were only decreased by 12 and 20%, respectively, as compared to cells maintained in glucose supplemented-medium
Summary
The regulation of the expression of adipose-related genes, i.e., aP2, adipsin, and glycerophosphate dehydrogenase (GPDH) by growth hormone (GH) and polyamines, as well as the role of fatty acids, have been investigated in polyaminedependent Ob1754 cells and Ob1771 preadipose cells. To delineate more precisely the effects of spermidine accumulation on that process, we have investigated the regulation of the expression of aP2, adipsin, and G P D H genes in the variant cell line Ob1754 In these cells no rise in spermidine level takes place despite the presence of G H ; chronic exposure of the cells to a mixture of putrescine and MGBG, a competitive inhibitor of S-adenosyl-methionine decarboxylase, leads to a rise in the cell content of spermidine similar to that occurring during differentiation of G H treated Ob1771 and 3T3-F442A cells; this rise is accompanied by terminal differentiation [12, 13]. Fatty acids or fatty acid metabolites appear to activate the aP2 gene and subsequently to modulate its expression
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