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Contenuto archiviato il 2024-04-30

Transcriptional and allosteric regulation of liver carnitine palmitoyl transferase i - l-cpt i- in a non ketogenic mammal

Obiettivo



Research objectives and content
Carnitine Palmitoyl Tansferase (CPT) system plays a central role in fuel homeostasis since it controls the entry of fatty acids within the mitochondria. CPT I, the outer membrane enzyme of mitochondrial CPT, plays a major role in the activation of Beta-oxidation and ketogenesis after birth. However, in pigs, Beta-oxidation and ketogenesis remain very low during the neonatal period and most of the fatty acids are esterified. In order to elucidate the mechanisms responsible for this peculiar metabolism we plan to study the gene expression of the liver isoform of CPT I (L-CPT I). We will use a previously isolated truncated clone of pig L-CPT I to isolate a full length cDNA and a genomic clone carrying the 5' flanking region of the L-CPT I gene. We will also study the tissue distribution of pig L-CPT I and its expression pattern during development and starvation. In addition we will express the enzyme in eukaryotic cells (COS) in order to determine its sensitivity to malonyl CoA. Finally, the transcriptional regulation of L-CPT I by Peroxisome Proliferator Receptors (PPAR) and cAMP to activate L-CPT I transcription will be studied.
Training content (objective, benefit and expected impact)
This work will allow us to understand, at the molecular level, the lipid metabolism in a non ketogenic mammal. This study will also provide a better understanding of how the CPT system deals with metabolic destination of long-chain fatty acids.
We expect to defend this work as Doctoral Thesis. If we achieve our goals, the data will be submitted for publication.
Links with industry / industrial relevance (22)
The high mortality of mammalian neonates during early postnatal period remains a significant problem in agricultural sciences. In 1991, the U.S. Department of Agriculture showed that 15% of the new-born piglets do not survive the weaning period. Moreover, 75% of these deaths occur within the first three days of life. Because fat represents an important source of energy for the new-born, it is crucial to understand the regulation and ontogeny of fatty acid oxidation during the perinatal period. Such a study could help in a near future to design strategies of metabolic ingeniery that would improve the survival of commercial pigs.

Campo scientifico (EuroSciVoc)

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RGI - Research grants (individual fellowships)

Coordinatore

Universitat de Barcelona
Contributo UE
Nessun dato
Indirizzo
S/N,Avenida Joan XXIII
08028 Barcelona
Spagna
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Partecipanti (1)