Mouse carnitine–acylcarnitine translocase (CACT) is transcriptionally regulated by PPARα and PPARδ in liver cells

Gutgesell, Anke; Wen, Gaiping; König, Bettina; Koch, Alexander; Spielmann, Julia; Stangl, Gabriele I.; Eder, Klaus; Ringseis, Robert

doi:10.1016/j.bbagen.2009.06.012

Cited by 25 publications

(22 citation statements)

References 33 publications

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“…Among the many modulators, Car has a key role in oxidation of long chain fatty acids, the transport of which from the cytosol into the mitochondrial matrix for subsequent ␤-oxidation is Car-dependent (16,20,21). Therefore, to examine whether the AGMinduced reduction of tissue fat is related to improved Car/AcylCar status, we determined the Car and AcylCar profiling in plasma and various tissues.…”

Section: Resultsmentioning

confidence: 99%

“…PPAR␣ is considered a master transcriptional regulator of lipid metabolism and energy homeostasis (11)(12)(13)(14)(15)(16)(17). PPAR␣-dependent gene transcription may be initiated by a ligand including fatty acids and/or by phosphorylation mediated via cAMP-PKA signaling (11,12).…”

Section: Contribution Of the Present Investigation To Understanding Tmentioning

confidence: 99%

“…Car facilitates the translocation of long chain fatty acids from the cytosol into the mitochondrial matrix for subsequent ␤-oxidation. This translocation is mediated via Car-acyltransferase, Car-acylcarnitine translocase, and Car-palmitoyltransferase (15,16). In addition, Car and its acylcarnitine (AcylCar) esters are essential metabolites that have a number of indispensable functions in bioenergetics, mitochondrial function, and intermediary and carbohydrate metabolism (15,16,20,21).…”

mentioning

confidence: 99%

“…Although dietary supplementation of Car may attenuate these metabolic disorders (40), the effectiveness of Car intervention may be limited due to malfunction of Car transporters in obesity and HFD (16,40,56). Therefore, the demonstration that AGM up-regulates genes responsible for Car biosynthesis and transport (Figs.…”

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confidence: 99%

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The Molecular and Metabolic Influence of Long Term Agmatine Consumption

Nissim

Horyn

Daikhin

et al. 2014

Journal of Biological Chemistry

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Background:Little is known about the molecular and metabolic impact of agmatine consumption. Results: We scrutinized the impact of long term agmatine treatment on whole body metabolic profiling and gene expression in rats. Agmatine elevated [cAMP] and triggered widespread changes in gene expression and metabolomic profiling. Conclusion: Agmatine influences on metabolism may be mediated via cAMP-PKA. Significance: Agmatine may curtail the metabolic and hormonal derangements associated with obesity.

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Section: Resultsmentioning

confidence: 99%

Section: Contribution Of the Present Investigation To Understanding Tmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The Molecular and Metabolic Influence of Long Term Agmatine Consumption

Nissim

Horyn

Daikhin

et al. 2014

Journal of Biological Chemistry

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“…Endogenous ligand-activation is mediated by NEFA and, physiologically occurs during fasting when NEFA are released from adipose tissue und taken up into liver, muscle and other tissues [9,10]. Transcriptional regulation of genes by PPARs is mediated by binding of activated PPAR/retinoid X receptor heterodimers to specific DNA sequences, called peroxisome proliferator response elements, present in and around the promoter of target genes [8,11,12]. Typical PPARα and PPARδ target genes are involved in all aspects of fatty acid catabolism, such as fatty acid uptake, intracellular fatty acid transport, mitochondrial fatty acid import, and peroxisomal and mitochondrial fatty acid oxidation [8,13].…”

Section: Introductionmentioning

confidence: 99%

Pharmacological doses of niacin stimulate the expression of genes involved in carnitine uptake and biosynthesis and improve the carnitine status of obese Zucker rats

Couturier

Ringseis

Most

et al. 2014

BMC Pharmacol Toxicol

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BackgroundActivation of peroxisome proliferator-activated receptor (PPAR)α and PPARδ causes an elevation of tissue carnitine concentrations through induction of genes involved in carnitine uptake [novel organic cation transporter 2, (OCTN2)], and carnitine biosynthesis [γ-butyrobetaine dioxygenase (BBD), 4-N-trimethyl-aminobutyraldehyde dehydrogenase (TMABA-DH)]. Recent studies showed that administration of the plasma lipid-lowering drug niacin causes activation of PPARα and/or PPARδ in tissues of obese Zucker rats, which have a compromised carnitine status and an impaired fatty acid oxidation capacity. Thus, we hypothesized that niacin administration to obese Zucker rats is also able to improve the diminished carnitine status of obese Zucker rats through PPAR-mediated stimulation of genes involved in carnitine uptake and biosynthesis.MethodsTo test this hypothesis, we used plasma, muscle and liver samples from a recent experiment with obese Zucker rats, which were fed either a niacin-adequate diet (30 mg niacin/kg diet) or a diet with a pharmacological niacin dose (780 mg niacin/kg diet), and determined concentrations of carnitine in tissues and mRNA and protein levels of genes critical for carnitine homeostasis (OCTN2, BBD, TMABA-DH). Statistical data analysis of all data was done by one-way ANOVA, and Fisher’s multiple range test.ResultsRats of the obese niacin group had higher concentrations of total carnitine in plasma, skeletal muscle and liver, higher mRNA and protein levels of OCTN2, BBD, and TMABA-DH in the liver and higher mRNA and protein levels of OCTN2 in skeletal muscle than those of the obese control group (P < 0.05), whereas rats of the obese control group had lower concentrations of total carnitine in plasma and skeletal muscle than lean rats (P < 0.05).ConclusionThe results show for the first time that niacin administration stimulates the expression of genes involved in carnitine uptake and biosynthesis and improves the diminished carnitine status of obese Zucker rats. We assume that the induction of genes involved in carnitine uptake and biosynthesis by niacin administration is mediated by PPAR-activation.

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Monocarboxylate transporter 1 and CD147 are up‐regulated by natural and synthetic peroxisome proliferator‐activated receptor α agonists in livers of rodents and pigs

König

Fischer

Schlotte

et al. 2010

Molecular Nutrition Food Res

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Monocarboxylate transporter (MCT)-1 mediates the transport of ketone bodies and other monocarboxylic acids across the plasma membrane. MCT1 is up-regulated by peroxisome proliferator-activated receptor (PPAR)-alpha, a transcription factor that mediates the adaptive response to fasting by up-regulation of genes involved in fatty acid oxidation and ketogenesis. Here, we show for the first time that MCT1 is up-regulated by dietary natural PPAR-alpha agonists. Both, an oxidized fat and conjugated linoleic acids increased MCT1 mRNA concentration in the liver of rats. Also, in the liver of pigs as non-proliferating species MCT1 was up-regulated upon PPAR-alpha activation by clofibrate, oxidized fat and fasting. Concomitant with up-regulation of MCT1, mRNA level of CD147 was increased in livers of rats and pigs. CD147 is a plasma membrane glycoprotein that is required for translocation and transport activity of MCT1. CD147 mRNA increase upon PPAR-alpha activation could not be observed in mice lacking PPAR-alpha, which also fail in up-regulation of MCT1 indicating a co-regulation of MCT1 and CD147. Analysis of the 5'-flanking region of mouse MCT1 gene by reporter gene assay revealed that promoter activity of mouse MCT1 was not induced by PPAR-alpha, indicating that the 5'-flanking region is not involved in MCT1 regulation by PPAR-alpha.

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Mouse carnitine–acylcarnitine translocase (CACT) is transcriptionally regulated by PPARα and PPARδ in liver cells

Cited by 25 publications

References 33 publications

The Molecular and Metabolic Influence of Long Term Agmatine Consumption

The Molecular and Metabolic Influence of Long Term Agmatine Consumption

Pharmacological doses of niacin stimulate the expression of genes involved in carnitine uptake and biosynthesis and improve the carnitine status of obese Zucker rats

Monocarboxylate transporter 1 and CD147 are up‐regulated by natural and synthetic peroxisome proliferator‐activated receptor α agonists in livers of rodents and pigs

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