Induction of the acyl-coenzyme A synthetase gene by fibrates and fatty acids is mediated by a peroxisome proliferator response element in the C promoter.

The long-chain acyl-coenzyme A synthetase (ACS) gene gives rise to three transcripts containing different first exons preceded by specific regulatory regions A, B, and C. Exon-specific oligonucleotide hybridization indicated that only A-ACS mRNA is expressed in rat liver. Fibrate administration induced liver C-ACS strongly and A-ACS mRNA to a lesser extent.

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Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes. Homology to peroxisome proliferator-activated receptors.

Exposure of preadipocytes to long chain fatty acids induces expression of several gene markers of adipocyte differentiation. This report describes the cloning, from a preadipocyte library, of a cDNA encoding a fatty acid-activated receptor, FAAR. The cDNA had the characteristics and ligand-binding domains of nuclear hormone receptors and encoded a 440 amino acid protein related to peroxisome proliferator-activated receptors, PPAR.

Fatty acids and adipose cell differentiation.

Fatty acids are important metabolic substrates for adipose tissue. In preadipose cells, fatty acids are also potent inducers of various genes encoding proteins directly involved in fatty acid metabolism. On a longer-term basis, fatty acids induce the terminal differentiation of preadipose to adipose cells.

Evidence for a common mechanism of action for fatty acids and thiazolidinedione antidiabetic agents on gene expression in preadipose cells.

In diabetic rodents, thiazolidinediones are able to improve insulin sensitivity of target tissues and to reverse, at least partially, the diabetic state. The effects of these drugs on phenotypic expression in various tissues, including adipose tissue, have been reported. We report here that a new thiazolidinedione compound, BRL 49653, exerts, in preadipose cells, potent effects on the expression of genes encoding proteins involved in fatty acid metabolism.

Fatty acids and retinoids act synergistically on adipose cell differentiation.

Fatty acids and retinoids have been recently reported to act as positive effectors of adipose cell differentiation. Treatment of Ob1771 preadipose cells with selective agonists of retinoic acid receptors (RARs) in the presence of alpha-bromopalmitate, a non-metabolized fatty acid, led to a potent synergy in regard to the differentiation process, as assayed by the activity of glycerol-3-phosphate dehydrogenase. The most potent synergy was observed with compound CD 367, a potent agonist of RARs as well as with compound Am 580, a specific agonist of RAR alpha.

Expression cloning in K+ transport defective yeast and distribution of HBP1, a new putative HMG transcriptional regulator.

The rat HBP1 cDNA was cloned by its capacity to suppress the potassium transport-defective phenotype of mutant Saccharomyces cerevisiae cells. HBP1 cDNA encodes a 513 amino acids protein which, unexpectedly, does not share any homology with K+ transporters or K+ channels. However, a search in protein databases reveals that HBP1 contains a putative DNA-binding domain called HMG-box.

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Retinoids are positive effectors of adipose cell differentiation.

Retinoids, especially all-trans retinoic acid (t-RA), have been reported in the last decade to inhibit the differentiation of preadipose cells. In those studies, however, the concentrations of t-RA were supraphysiological (0.1-10 microM range).

Fatty acids as signal transducing molecules: involvement in the differentiation of preadipose to adipose cells.

Fatty acids are important metabolic substrates for adipose tissue and act, in preadipose cells, as potent inducers of various proteins directly involved in their metabolism. We have investigated the long-term effects of fatty acids on the conversion process of preadipose Ob1771 cells to adipose cells. Chronic exposure of cells to palmitate led, in a dose-dependent manner, to a strong stimulation of cell differentiation; this effect was confined to terminal events whereas fatty acids did not affect expression of early genes related to commitment of adipoblasts to preadipose cells.

Hormonal regulation of adipose differentiation.

Adipose differentiation is a multistep process with the following sequence: adipoblasts --> preadipocytes --> adipocytes. Adipogenic agents are only involved in the terminal differentiation of preadipocytes to adipocytes by means of circulating hormones (growth hormone, glucocorticoids, or triiodothyronine) and locally produced hormones (prostacyclin). Fatty acids also behave as hormones and act as transcriptional regulators of lipid-related genes.

Acyl-CoA synthetase mRNA expression is controlled by fibric-acid derivatives, feeding and liver proliferation.

Several enzymes of the beta-oxidation pathway have been shown to be induced after stimulation with peroxisomal proliferators, including several hypolipidemic drugs. We investigated the regulation of the long-chain-acyl-CoA synthetase (ACS) gene in the liver. Fenofibrate, a hypolipidemic drug and potent peroxisomal proliferator, induced ACS gene expression in several tissues.

Identification of 3',5'-cyclic adenosine monophosphate-inducible nuclear factors binding to the human urokinase promoter in mouse Sertoli cells.

Transcription factors which recognize both the SV40 promoter and the proximal promoter region of the human urokinase-type plasminogen activator (h-uPA) gene are present in nuclear extracts from primary cultures of mouse Sertoli cells; prolonged (more than 12 h) (Bu)2cAMP stimulation of Sertoli cells induces the formation of different specific DNA-protein complexes. A discrete region in the h-uPA promoter, between -54 and -42, is essential for the formation of the cAMP-induced DNA-protein complexes. Mutation of the sequence between -54 and -42 abolishes the response to cAMP of the proximal h-uPA promoter in Sertoli cells.