A high-fat diet increases l-carnitine synthesis through a differential maturation of the Bbox1 mRNAs. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue BBA - Biochimica et Biophysica Acta Année : 2013

A high-fat diet increases l-carnitine synthesis through a differential maturation of the Bbox1 mRNAs.

Résumé

l-carnitine is a key molecule in both mitochondrial and peroxisomal lipid metabolisms. l-carnitine is biosynthesized from gamma-butyrobetaine by a reaction catalyzed by the gamma-butyrobetaine hydroxylase (Bbox1). The aim of this work was to identify molecular mechanisms involved in the regulation of l-carnitine biosynthesis and availability. Using 3' RACE, we identified four alternatively polyadenylated Bbox1 mRNAs in rat liver. We utilized a combination of in vitro experiments using hybrid constructs containing the Bbox1 3' UTR and in vivo experiments on rat liver mRNAs to reveal specificities in the different Bbox1 mRNA isoforms, especially in terms of polyadenylation efficiency, mRNA stability and translation efficiency. This complex maturation process of the Bbox1 mRNAs in the liver was studied on rats fed a high-fat diet. High-fat diet selectively increased the level of three Bbox1 mRNA isoforms in rat liver and the alternative use of polyadenylation sites contributed to the global increase in Bbox1 enzymatic activity and l-carnitine levels. Our results show that the maturation of Bbox1 mRNAs is nutritionally regulated in the liver through a selective polyadenylation process to adjust l-carnitine biosynthesis to the energy supply.

Dates et versions

hal-00787886 , version 1 (13-02-2013)

Identifiants

Citer

Caroline Rigault, Françoise Le Borgne, Bassim Tazir, Alexandre Benani, Jean Demarquoy. A high-fat diet increases l-carnitine synthesis through a differential maturation of the Bbox1 mRNAs.. BBA - Biochimica et Biophysica Acta, 2013, 1831 (2), pp.370-7. ⟨10.1016/j.bbalip.2012.10.007⟩. ⟨hal-00787886⟩
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