Journal of Applied Genetics

, Volume 51, Issue 2, pp 193–197 | Cite as

High-fat diet leads to a decreased methylation of theMc4r gene in the obese BFMI and the lean B6 mouse lines

  • S. Widiker
  • S. Kärst
  • A. Wagener
  • G. A. Brockmann
Short Communication

Abstract

The melanocortin-4 receptor (Mc4r) plays an important role in body-weight regulation. This study examines the methylation status and expression levels of theMc4r gene in response to a standard and a high-fat diet in the obese Berlin fat mouse inbred (BFMI) line and the lean C57BL/6NCrl (B6) line ofMus musculus. The methylation status of CpG sites located within theMc4r exon was analyzed by bisulfite genomic sequencing of genomic DNA of brain tissues, and gene expression analysis was performed by real-time PCR. In both lines, the methylation of CpGs 1–8 (near the transcription start) was lower than methylation of CpGs 9–16 (located towards the end of the selected amplicon). On the standard diet, the methylation status did not differ between the lines. In response to high-fat diet, methylation of the CpGs near the transcription start was decreased in both lines. TheMc4r gene expression, however, was only marginally increased in BMFI mice, whereas there was no change in B6 mice. The results suggest that a long-term high-fat diet might have an effect on the methylation status of theMc4r gene. However, the effect of methylation onMc4r expression seems to be a variable compensated by other regulating factors in a line-specific manner.

Keywords

epigenetics gene expression methylation pattern Mus musculus obesity 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Boghossian S, Park M, York DA, 2010. Melanocortin activity in the amygdala controls appetite for dietary fat. Am J Physiol Regul Integr Comp Physiol 298: 385–393.Google Scholar
  2. Boyes J, Bird A, 1991. DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell 64: 1123–1134.CrossRefPubMedGoogle Scholar
  3. Chen AS, Metzger JM, Trumbauer ME, Guan XM, Yu H, Frazier EG, et al. 2000. Role of the melanocortin-4 receptor in metabolic rate and food intake in mice. Transgenic Res 9: 145–154.CrossRefPubMedGoogle Scholar
  4. Dolinoy DC, Huang D, Jirtle RL, 2007. Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci USA 104: 13056–13061.CrossRefPubMedGoogle Scholar
  5. Fan S, Zhang X, 2009. CpG island methylation pattern in different human tissues and its correlation with gene expression. Biochem Biophys Res Commun 383: 421–425.CrossRefPubMedGoogle Scholar
  6. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, et al. 2005. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A 102: 10604–10609.CrossRefPubMedGoogle Scholar
  7. Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, et al. 1997. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88: 131–141.CrossRefPubMedGoogle Scholar
  8. Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, et al. 1998. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 19: 187–191.CrossRefPubMedGoogle Scholar
  9. Lewin J, Schmitt AO, Adorján P, Hildmann T, Piepenbrock C, 2004. Quantitative DNA methylation analysis based on four-dye trace data from direct sequencing of PCR amplificates. Bioinformatics 2004: 1–8.Google Scholar
  10. Livak KJ, Schmittgen TD, 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2-[delta][delta]CT-method. Methods 25: 402–408.CrossRefPubMedGoogle Scholar
  11. Loos RJ, Lindgren CM, Li S, Wheeler E, Zhao JH, Prokopenko I, Inouye M, et al. 2008. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet 40: 768–775.CrossRefPubMedGoogle Scholar
  12. Meyer CW, Wagener A, Rink N, Hantschel C, Heldmaier G, Klingenspor M, Brockmann GA, 2009. High energy digestion efficiency and altered lipid metabolism contribute to obesity in BFMI mice. Obesity 17: 1988–1993.CrossRefPubMedGoogle Scholar
  13. Mountjoy KG, Wong J, 1997. Obesity, diabetes and functions for proopiomelanocortin-derived peptides. Mol Cell Endocrinol 128: 171–177.CrossRefPubMedGoogle Scholar
  14. Reifsnyder PC, Churchill G, Leiter EH, 2000. Maternal environment and genotype interact to establish diabesity in mice. Genome Res 10: 1568–1578.CrossRefPubMedGoogle Scholar
  15. Robertson KD, 2005. DNA methylation and human disease. Nat Rev Genet 6: 597–610.CrossRefPubMedGoogle Scholar
  16. Rożen S, Skaletsky HJ, 2000. Bioinformatics Methods and Protocols: Method in Molecular Biology, Humana Press, Totowa, NJ: 365–386.Google Scholar
  17. Tinsley FC, Taicher GZ, Heiman ML, 2004. Evaluation of a quantitative magnetic resonance method for mouse whole body composition analysis. Obes Res 12: 150–160.CrossRefPubMedGoogle Scholar
  18. Wagener A, Schmitt AO, Aksu S, Schlote W, Neuschl C, Brockmann GA, 2006. Genetic, sex, and diet effects on body weight and obesity in the Berlin Fat Mouse Inbred lines. Physiol Genomics 27: 264–270.CrossRefPubMedGoogle Scholar

Copyright information

© Institute of Plant Genetics, Polish Academy of Sciences, Poznan 2010

Authors and Affiliations

  • S. Widiker
    • 1
  • S. Kärst
    • 1
  • A. Wagener
    • 1
  • G. A. Brockmann
    • 1
  1. 1.Breeding Biology and Molecular Genetics, Institute of Animal SciencesHumboldt-University of BerlinBerlinGermany

Personalised recommendations