Group Name:

Cell Signalling: Metabolic and Hormonal Control of Gene Expression

Research Topics:

Our main aim in the last few years has been to study how genes that play a role in the control of FA oxidation and ketogenesis, respond to different metabolic signals. At this moment, to progress in our knowledge, we want to investigate how products of these pathways affect general energetic homeostasis through several different mechanisms, such as food intake control, chromatin structure, transcription or enzymatic activity. In general terms, we are interested in studying: i) the ways of control of CPT1C gene and protein in brain; ii) how activity of CPT system genes is affected by histones/proteins acetylation and by SIRT1 deacetylase; and iii) the generation of a tissue-specific knock out of HMGCS2 gene to study the role of ketone bodies as signalling molecules in controlling diverse pathways. The results of these investigations will give us a better knowledge of several diseases like cardiovascular, hyperlipidemia, obesity or insulin resistance.

Group’s Members:

Diego Haro Bautista, Professor

Pedro F. Marrero, Professor

Joana Relat Pardo, Associated Professor

Francesca Margalida Aguiló Payeras (FPU fellowship)

Mar Gacias Monserrat (FPU fellowship)

Magdalena Pujol Vidal (FI fellowship)

Anna Vilà Brau (FI fellowship)

Ana Luisa Coelho Sousa (FCT fellowship)

María José Aguilar Perez, Technician

Recent Publications:

  1. Puig T, Vázquez-Martín A, Relat J, Pétriz J, Menéndez JA, Porta R, Casals G, Marrero PF, Haro D, Brunet J, Colomer R.

Fatty acid metabolism in breast cancer cells: differential inhibitory effects of epigallocatechin gallate (EGCG) and C75.

Breast Cancer Res Treat. 2008 Jun;109(3):471-9. Epub 2007 Sep 28.

  1. Camarero N, Mascaró C, Mayordomo C, Vilardell F, Haro D, Marrero PF.

Ketogenic HMGCS2 Is a c-Myc target gene expressed in differentiated cells of human colonic epithelium and down-regulated in colon cancer.

Mol Cancer Res. 2006 Sep;4(9):645-53. Epub 2006 Aug 28.

  1. Napal L, Marrero PF, Haro D.

An intronic peroxisome proliferator-activated receptor-binding sequence mediates fatty acid induction of the human carnitine palmitoyltransferase 1A.

J Mol Biol. 2005 Dec 9;354(4):751-9. Epub 2005 Oct 21.

  1. Nicot C, Napal L, Relat J, González S, Llebaria A, Woldegiorgis G, Marrero PF, Haro D.

C75 activates malonyl-CoA sensitive and insensitive components of the CPT system.

Biochem Biophys Res Commun. 2004 Dec 17;325(3):660-4.

  1. Relat J, Nicot C, Gacias M, Woldegiorgis G, Marrero PF, Haro D.

Pig muscle carnitine palmitoyltransferase I (CPTI beta), with low Km for carnitine and low sensitivity to malonyl-CoA inhibition, has kinetic characteristics similar to those of the rat liver (CPTI alpha) enzyme.

Biochemistry. 2004 Oct 5;43(39):12686-91.

  1. Baldán A, Relat J, Marrero PF, Haro D.

Functional interaction between peroxisome proliferator-activated receptors-alpha and Mef-2C on human carnitine palmitoyltransferase 1beta (CPT1beta) gene activation.

Nucleic Acids Res. 2004 Sep 8;32(16):4742-9. Print 2004.

  1. Napal L, Dai J, Treber M, Haro D, Marrero PF, Woldegiorgis G.

A single amino acid change (substitution of the conserved Glu-590 with alanine) in he C-terminal domain of rat liver carnitine palmitoyltransferase I increases its malonyl-CoA sensitivity close to that observed with the muscle isoform of the enzyme.

J Biol Chem. 2003 Sep 5;278(36):34084-9.

  1. Camarero N, Nadal A, Barrero MJ, Haro D, Marrero PF.

Histone deacetylase inhibitors stimulate mitochondrial HMG-CoA synthase gene expression via a promoter proximal Sp1 site.

Nucleic Acids Res. 2003 Mar 15;31(6):1693-703.

  1. Barrero MJ, Camarero N, Marrero PF, Haro D.

Control of human carnitine palmitoyltransferase II gene transcription by peroxisome proliferator-activated receptor through a partially conserved peroxisome proliferator-responsive element.

Biochem J. 2003 Feb 1;369(Pt 3):721-9.

  1. Nadal A, Marrero PF, Haro D.

Down-regulation of mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A synthase gene by insulin. Role of the forkhead transcription factor FKHRL1.

Biochem J. 2002 ; 366: 288-97

  1. Nicot C, Relat J, Woldegiorgis G, Haro D, Marrero PF.

Pig liver carnitine palmitoyltransferase. Chimera studies show that both the N- and C-terminal regions of the enzyme are important for the unusual high malonyl-CoA sensitivity.

J Biol Chem. 2002; 277:10044-10049. IF: 7,368

 Last 5 years Financed Proyects:

FINANCING INSTITUTION: Ministerio de Educación y Ciencia

PROGRAM: Biología Fundamental (BFU)

TÍTLE: Role of Fatty acid Oxidation and Ketogenesis Energetic Homeostasis.

PRINCIPAL INVESTIGATOR: Pedro F. Marrero

 

FINANCING INSTITUTION: Ministerio de Turismo y Comercio

PROGRAM: Cenit

TÍTLE: Ocnosis.

PRINCIPAL INVESTIGATOR: Diego Haro y Pedro F. Marrero

 

FINANCING INSTITUTION: Ministerio de Sanidad y Consumo

PROGRAM: Redes temáticas de investigación cooperativa.

TÍTLE: Determinantes moleculares del metabolismo y la nutrición.

PRINCIPAL INVESTIGATOR: Diego Haro Bautista

 

FINANCING INSTITUTION: Generalitat de Catalunya

PROGRAM: Grups Consolidats de Recerca.

TÍTLE: Senyalització Cel·lular.

PRINCIPAL INVESTIGATOR: Diego Haro Bautista

 

FINANCING INSTITUTION: Ministerio de Educación y Ciencia

PROGRAM: Biología Fundamental (BFU).

TÍTLE: Control de la expresión génica de los genes involucrados en el importe de los ácidos grasos a la mitocondria.

PRINCIPAL INVESTIGATOR: Diego Haro Bautista

 

FINANCING INSTITUTION: Ministerio de Educación y Ciencia

PROGRAM: Biología Fundamental (BFU).

TÍTLE: Control of pathways involved in the production and utilisation of ketone bodies.

PRINCIPAL INVESTIGATOR: Pedro F. Marrero