Cyclic AMP and Fatty Acids Increase Carnitine Palmitoyltransferase I Gene Transcription in Cultured Fetal Rat Hepatocytes

Chatelain, Florence; Kohl, Claude; Esser, Victoria; McGarry, Julie; Girard, Jean; Pégorier, Jean‐Paul

doi:10.1111/j.1432-1033.1996.00789.x

Cited by 116 publications

(80 citation statements)

References 61 publications

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“…Transcription of the L-CPT I gene is elevated in the livers of rats on high fat diets and decreased in the livers of rats on high carbohydrate diets [19]. In isolated hepatocytes, insulin inhibits transcription of the L-CPT I gene.…”

Section: Tissue-specific Expression Of the L-cpt I Genementioning

confidence: 95%

“…Expression of the gene for L-CPT I is regulated during development and in response to dietary modifications [19]. As the first step towards investigating the transcriptional control of L-CPT I, our goal was to clone the promoter regulatory region of this gene.…”

Section: Identification Of the Rat L-cpt I Genementioning

confidence: 99%

“…Long-chain fatty acids and peroxisomal proliferator compounds such as clofibrate will also stimulate transcription of the gene. Transcription of the L-CPT I gene is increased in the liver at birth, providing the capacity to generate ketone bodies and to oxidize fatty acids from mothers' milk [19].…”

Section: Tissue-specific Expression Of the L-cpt I Genementioning

confidence: 99%

“…These observations suggest an important role for hormones and diet in controlling L-CPT I expression. Transcription of the gene is inhibited by insulin but stimulated by cAMP, fatty acids and peroxisomal proliferators [19]. L-CPT I mRNA abundance is increased five-fold and 14-fold in hyperthyroidism and streptozotocin induced diabetes, respectively [3,20].…”

Section: Introductionmentioning

confidence: 99%

“…CPT II is expressed before birth and its activity and mRNA abundance are unchanged by fatty acids or insulin [18,19]. Only clofibrate is able to stimulate CPT II gene expression [19].…”

Section: Introductionmentioning

confidence: 99%

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Cloning and characterization of the promoter for the liver isoform of the rat carnitine palmitoyltransferase I (L-CPT I) gene

Park

Steffen

Song

et al. 1998

Biochemical Journal

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Carnitine palmitoyltransferase I (CPT I) catalyses the transfer of long chain fatty acids to carnitine for translocation across the mitochondrial inner membrane. The cDNAs of two isoforms of CPT I, termed the hepatic and muscle isoforms, have been cloned. Expression of the hepatic CPT I gene (L-CPT I) is subject to developmental, hormonal and tissue specific regulation. We have cloned the promoter of the L-CPT I gene from a rat genomic library. In the L-CPT I gene, there are two exons 5ʹ to the exon containing the ATG that initiates translation. Exon 1 and the 5ʹ end of exon 2 contain sequences that were not previously described in the rat L-CPT I cDNA. There is an alternatively spliced form of the L-CPT I mRNA in which exon 2 is skipped. The proximal promoter of the L-CPT I gene is extremely GC rich and does not contain a TATA box. There are several putative Sp1 binding sites near the transcriptional start site. A 190 base pair fragment of the promoter can efficiently drive transcription of luciferase and CAT (chloramphenicol acetyltransferase) reporter genes transiently transfected into HepG2 cells. Sequences in both the first intron and the promoter contribute to basal expression. Our results provide the foundation for further studies into the regulation of L-CPTI gene expression.

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Section: Tissue-specific Expression Of the L-cpt I Genementioning

confidence: 95%

Section: Identification Of the Rat L-cpt I Genementioning

confidence: 99%

Section: Tissue-specific Expression Of the L-cpt I Genementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…CPT II is expressed before birth and its activity and mRNA abundance are unchanged by fatty acids or insulin [18,19]. Only clofibrate is able to stimulate CPT II gene expression [19].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cloning and characterization of the promoter for the liver isoform of the rat carnitine palmitoyltransferase I (L-CPT I) gene

Park

Steffen

Song

et al. 1998

Biochemical Journal

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Cancer and anticancer therapy-induced modifications on metabolism mediated by carnitine system

et al. 2000

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An efficient regulation of fuel metabolism in response to internal and environmental stimuli is a vital task that requires an intact carnitine system. The carnitine system, comprehensive of carnitine, its derivatives, and proteins involved in its transformation and transport, is indispensable for glucose and lipid metabolism in cells. Two major functions have been identified for the carnitine system: (1) to facilitate entry of long-chain fatty acids into mitochondria for their utilization in energy-generating processes; (2) to facilitate removal from mitochondria of short-chain and medium-chain fatty acids that accumulate as a result of normal and abnormal metabolism. In cancer patients, abnormalities of tumor tissue as well as nontumor tissue metabolism have been observed. Such abnormalities are supposed to contribute to deterioration of clinical status of patients, or might induce cancerogenesis by themselves. The carnitine system appears abnormally expressed both in tumor tissue, in such a way as to greatly reduce fatty acid beta-oxidation, and in nontumor tissue. In this view, the study of the carnitine system represents a tool to understand the molecular basis underlying the metabolism in normal and cancer cells. Some important anticancer drugs contribute to dysfunction of the carnitine system in nontumor tissues, which is reversed by carnitine treatment, without affecting anticancer therapeutic efficacy. In conclusion, a more complex approach to mechanisms that underlie tumor growth, which takes into account the altered metabolic pathways in cancer disease, could represent a challenge for the future of cancer research.

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Insulin Regulation of Ketone Body Metabolism

Ciaraldi

Henry

2004

International Textbook of Diabetes Mellitus

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The overarching concern in the hormonal control of ketone body metabolism is the insulin level. In circumstances where insulin levels are relatively high, such as the fed state, both substrate (free fatty acid, [FFA]) availability and FFA oxidation are suppressed, directing FFA to storage and employing glucose to meet the energy needs of the body. In situations of relative insulin deficiency, such as starvation or type I diabetes, FFA oxidation is increased, driving the production of alternative energy‐producing substrates, ketone bodies, for use by the brain, as well as peripheral tissues. Insulin influences the activity of three key processes: FFA availability (lipolysis), ketone body production (ketogenesis), and disposal in peripheral tissues. All of these processes can be altered in pathophysiologic conditions such as type 1 and type 2 diabetes, obesity, starvation, and hyperthyroidism. The key control point is carnitine palmitoyltransferase‐I (CPT‐I), which mediates the passage of long chain fatty acyl coenzyme A (FA‐CoA) esters across the outer mitochondrial membrane, prior to oxidation or ketogenesis. Insulin regulates CPT‐I both at the level of gene transcription and by influencing the affinity for allosteric modulators. Regulation of hepatic CPT‐I expression or activity holds potential significance as an approach for controlling hyperglycemia and insulin resistance.

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Cyclic AMP and Fatty Acids Increase Carnitine Palmitoyltransferase I Gene Transcription in Cultured Fetal Rat Hepatocytes

Cited by 116 publications

References 61 publications

Cloning and characterization of the promoter for the liver isoform of the rat carnitine palmitoyltransferase I (L-CPT I) gene

Cloning and characterization of the promoter for the liver isoform of the rat carnitine palmitoyltransferase I (L-CPT I) gene

Cancer and anticancer therapy-induced modifications on metabolism mediated by carnitine system

Insulin Regulation of Ketone Body Metabolism

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