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Hypothalamic expression of porcine leptin receptor (LEPR), neuropeptide Y (NPY), and cocaine- and amphetamine-regulated transcript (CART) genes is influenced by LEPR genotype

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Abstract

The leptin receptor (LEPR) is a key gene in the control of food intake and energy homeostasis. The sequence variant LEPR{NM_001024587.1}:c.1987C>T has been associated with growth, fatness, and body composition in several pig populations. The purpose of this work was to confirm the phenotypic effects of this SNP in two new experimental backcrosses involving Iberian, Landrace, and Duroc breeds, and to evaluate the quantitative effects of the SNP on the hypothalamic expression of LEPR and two other downstream genes. Results indicate significant additive effects of the SNP on body weight, back fat thickness, and hypothalamic LEPR gene expression in both populations. Allele T fixed in the Iberian breed is systematically associated with a higher growth and fat deposition and leads to an intense reduction of LEPR hypothalamic expression, providing new functional evidence that supports the causality of the analyzed SNP with respect to previously reported and newly observed phenotypic effects. Also, some effects of the LEPR genotype on neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) genes are detected, although they are conditioned by the breed. Finally, a change in mRNA structure and an increase in free energy is predicted for allele T, agreeing with a cis-acting functional effect on mRNA stability, which also supports the causality hypothesis. The lower expression of the LEPR gene in Iberian pigs fits with obesity by leptin resistance observed in this breed. A reduction in leptin signaling could thus be considered one of the determinants of the obese phenotype characteristic of Iberian breed.

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Acknowledgments

This study was supported by INIA CPE03-010 and MICINN AGL2008-04818-C03 grants. We are grateful to Wendy Rauw for useful revision of the manuscript, and to Nines López (INIA), Ingrid Riart (IRTA), and José María Borrás and Felix Grau (INGA FOOD S.A.) for technical assistance in sampling, genotyping, phenotyping, and animal management.

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Authors and Affiliations

  1. Departmento de Mejora Genética Animal, INIA, Madrid, Spain

    Cristina Óvilo, Almudena Fernández, Ana I. Fernández, Rita Benítez, Yolanda Nuñez, Carmen Rodríguez & Luis Silió

  2. Departmento de Ciència Animal i dels Aliments, Facultat de Veterinària, UAB, Bellaterra, Barcelona, Spain

    Josep M. Folch

  3. Area Producció Animal, UdL-IRTA, Lleida, Spain

    Luis Varona

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  1. Cristina Óvilo
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  2. Almudena Fernández
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  6. Rita Benítez
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  8. Carmen Rodríguez
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  9. Luis Silió
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Correspondence to Cristina Óvilo.

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Óvilo, C., Fernández, A., Fernández, A.I. et al. Hypothalamic expression of porcine leptin receptor (LEPR), neuropeptide Y (NPY), and cocaine- and amphetamine-regulated transcript (CART) genes is influenced by LEPR genotype. Mamm Genome 21, 583–591 (2010). https://doi.org/10.1007/s00335-010-9307-1

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