Regulation of liver carnitine palmitoyltransferase I gene expression by hormones and fatty acids

Centre de Recherche sur l'Endocrinologie Moléculaire et le Développement, UPR 1524 CNRS, 9 rue Jules Hetzel, 92190 Meudon, France.
Biochemical Society Transactions (Impact Factor: 3.19). 06/2001; 29(Pt 2):310-6. DOI: 10.1042/0300-5127:0290310
Source: PubMed


This brief review focuses on the transcriptional regulation of liver carnitine palmitoyltransferase I (L-CPT I) by pancreatic and thyroid hormones and by long-chain fatty acids (LCFA). Both glucagon and 3,3',5-tri-iodothyronine (T(3)) enhanced the transcription of the gene encoding L-CPT I, whereas insulin had the opposite effect. Interestingly, the transcriptional effect of T(3) required, in addition to the thyroid-responsive element, the co-operation of a sequence located in the first intron of L-CPT I gene. Non-esterified fatty acids rather than acyl-CoA ester or intra-mitochondrial metabolite were responsible for the transcriptional effect on the gene encoding L-CPT I. It was shown that LCFA and peroxisome proliferators stimulated L-CPT I gene transcription by distinct mechanisms. Peroxisome proliferator stimulated L-CPT I gene transcription through a peroxisome-proliferator-responsive element (PPRE) located at -2846 bp, whereas LCFA induced L-CPT I gene transcription through a peroxisome-proliferator-activated receptor alpha (PPARalpha)-independent mechanism owing to a sequence located in the first intron of the gene.

3 Reads
    • "In mammals, the role of hormones, e.g. glucagon and insulin, on the transcription of genes involved in lipid metabolism is well known (Girard et al., 1994; Louet et al., 2001; Saltiel and Kahn, 2001). In insects, hormones can also affect gene transcription . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Adipokinetic hormone (AKH) has been associated with the control of energy metabolism in a large number of arthropod species due to its role on the stimulation of lipid, carbohydrate and amino acid mobilization/release. In the insect Rhodnius prolixus, a vector of Chagas' disease, triacylglycerol (TAG) stores must be mobilized to sustain the metabolic requirements during moments of exercise or starvation. Besides the recent identification of the R. prolixus AKH peptide, other components required for the AKH signalling cascade and its mode of action remain uncharacterized in this insect. In the present study, we identified and investigated the expression profile of the gene encoding the AKH receptor of R. prolixus (RhoprAkhr). This gene is highly conserved in comparison to other sequences already described and its transcript is abundant in the fat body and the flight muscle of the kissing bug. Moreover, RhoprAkhr expression is induced in the fat body at moments of increased TAG mobilization; the knockdown of this gene resulted in TAG accumulation both in fat body and flight muscle after starvation. The inhibition of Rhopr-AKHR transcription as well as the treatment of insects with the peptide Rhopr-AKH in its synthetic form altered the transcript levels of two genes involved in lipid metabolism, the acyl-CoA-binding protein-1 (RhoprAcbp1) and the mitochondrial glycerol-3-phosphate acyltransferase (RhoprGpat1). These results indicate that the AKH receptor is regulated at transcriptional level and is required for TAG mobilization under starvation. In addition to the classical view of AKH as a direct regulator of enzymatic activity, we propose here that AKH signaling may account for the regulation of nutrient metabolism by affecting the expression profile of target genes. Copyright © 2015. Published by Elsevier Ltd.
    Insect Biochemistry and Molecular Biology 01/2016; in press. DOI:10.1016/j.ibmb.2015.06.013 · 3.45 Impact Factor
  • Source
    • "Acox1 mRNA expression increased steadily after birth, and this pattern has been shown at the protein level [25]. The pattern of Cpt1a expression that was observed in this study, induced at birth then markedly decreased at weaning, parallels Cpt1a expression profiles in rats at the mRNA, protein, and activity levels [26], [27], [28]. Pparα regulates the expression of Acox1 in adult mice [29]; however, the regulation of Cpt1a in mice is less explored. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The liver plays a central role in metabolic homeostasis by coordinating synthesis, storage, breakdown, and redistribution of nutrients. Hepatic energy metabolism is dynamically regulated throughout different life stages due to different demands for energy during growth and development. However, changes in gene expression patterns throughout ontogeny for factors important in hepatic energy metabolism are not well understood. We performed detailed transcript analysis of energy metabolism genes during various stages of liver development in mice. Livers from male C57BL/6J mice were collected at twelve ages, including perinatal and postnatal time points (n = 3/age). The mRNA was quantified by RNA-Sequencing, with transcript abundance estimated by Cufflinks. One thousand sixty energy metabolism genes were examined; 794 were above detection, of which 627 were significantly changed during at least one developmental age compared to adult liver. Two-way hierarchical clustering revealed three major clusters dependent on age: GD17.5-Day 5 (perinatal-enriched), Day 10-Day 20 (pre-weaning-enriched), and Day 25-Day 60 (adolescence/adulthood-enriched). Clustering analysis of cumulative mRNA expression values for individual pathways of energy metabolism revealed three patterns of enrichment: glycolysis, ketogenesis, and glycogenesis were all perinatally-enriched; glycogenolysis was the only pathway enriched during pre-weaning ages; whereas lipid droplet metabolism, cholesterol and bile acid metabolism, gluconeogenesis, and lipid metabolism were all enriched in adolescence/adulthood. This study reveals novel findings such as the divergent expression of the fatty acid β-oxidation enzymes Acyl-CoA oxidase 1 and Carnitine palmitoyltransferase 1a, indicating a switch from mitochondrial to peroxisomal β-oxidation after weaning; as well as the dynamic ontogeny of genes implicated in obesity such as Stearoyl-CoA desaturase 1 and Elongation of very long chain fatty acids-like 3. These data shed new light on the ontogeny of homeostatic regulation of hepatic energy metabolism, which could ultimately provide new therapeutic targets for metabolic diseases.
    PLoS ONE 08/2014; 9(8):e104560. DOI:10.1371/journal.pone.0104560 · 3.23 Impact Factor
  • Source
    • "In dairy cattle , the final step of endogenous carnitine synthesis only occurs in the liver and kidney via BBOX1 ( Vaz and Wanders , 2002 ) . Consistent with the stimula - tory effect of thyroid hormone on lipid metabolism and CPT - 1 activity ( Louet et al . , 2001 ) , thyroxine admin - istration increased hepatic BBOX1 expression , BBOX1 activity , and carnitine accumulation ( Galland et al . , 2002 ) . In contrast to early postpartal cows ( Schlegel et al . , 2012 ) , we observed a decrease in the expression of BBOX1 ( Figure 2 ) with feed restriction , suggest - ing a decrease in endogenous syn"
    [Show abstract] [Hide abstract]
    ABSTRACT: Abomasal carnitine infusion during acute feed restriction increases hepatic fatty acid oxidation and decreases liver lipid in dairy cows. Eight mid-lactation Holstein cows were used in a replicated 4 × 4 Latin square design with 14-d periods. A 2 × 2 factorial arrangement was used to determine the effects of water infusion + ad libitum dry matter intake (DMI), water infusion + restricted DMI (50% of previous 5-d average), l-carnitine infusion (20 g/d) + ad libitum DMI, or l-carnitine infusion + restricted DMI. Liver RNA from 7 healthy cows was used for transcriptome profiling using a bovine microarray. An ANOVA with a false discovery rate was used to identify treatment and interaction effects. A substantial transcriptome change was observed only with DMI restriction, resulting in 312 (155 downregulated, 157 upregulated) differentially expressed genes. Quantitative PCR was performed to verify microarray data and measure expression of additional genes not present on the microarray. The quantitative PCR data confirmed the effect of feed restriction but not of l-carnitine treatment. Feed restriction increased expression of GPX3 and of genes associated with gluconeogenesis (PC, PDK4), inflammation (SAA3), and signaling (ADIPOR2). In contrast, feed restriction downregulated BBOX, a key for l-carnitine biosynthesis, and the transcription factor HNF4A. The bioinformatics functional analysis of genes affected by DMI restriction uncovered biosynthesis of cholesterol and energy generation by mitochondrial respiration as the most relevant and inhibited functions. The data also indicated an increase of flux toward gluconeogenesis. We interpreted those results as a likely response of the liver to spare energy and provide glucose for the lactating mammary gland during feed deprivation.
    Journal of Dairy Science 02/2013; 96(4). DOI:10.3168/jds.2012-6036 · 2.57 Impact Factor
Show more