Paternal allele influences high fat diet-induced obesity

PLoS One. 2014 Jan 8;9(1):e85477. doi: 10.1371/journal.pone.0085477. eCollection 2014.

Abstract

C57BL/6J (B6) mice are susceptible to high-fat diet (HFD)-induced obesity and have been used in metabolism research for many decades. However, the genetic component of HFD-induced obesity has not yet been elucidated. This study reports evidence for a paternal transmission of HFD-induced obesity and a correlated expression of Igf2 and Peg3 (paternal expressed gene 3) imprinted genes. We found that PWK mice are resistant to HFD-induced obesity compared to C57BL/6J mice. Therefore, we generated and analyzed reciprocal crosses between these mice, namely; (PWK×B6) F1 progeny with B6 father and (B6×PWK) F1 progeny with PWK father. The (PWK×B6) F1 mice were more sensitive to diet-induced obesity compared to (B6×PWK) F1 mice, suggesting a paternal transmission of diet-induced obesity. Expression analysis of imprinted genes in adipocytes revealed that HFD influences the expression of some of the imprinted genes in adipose tissue in B6 and PWK mice. Interestingly, Igf2 and Peg3, which are paternally expressed imprinted genes involved in the regulation of body fat accumulation, were down-regulated in B6 and (PWK×B6) F1 mice, which are susceptible to HFD-induced obesity, but not in PWK and (B6×PWK) F1 mice, which are resistant. Furthermore, in vitro analysis showed that Igf2, but not Peg3, had an anti-inflammatory effect on TNF-α induced MCP-1 expression in adipocytes. Taken together, our findings suggest that the down-regulation of Igf2 and Peg3 imprinted genes in adipocytes may be involved in the paternal transmission of HFD-induced obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Crosses, Genetic
  • Diet, High-Fat*
  • Dietary Fats / adverse effects
  • Female
  • Genomic Imprinting*
  • Inheritance Patterns
  • Insulin-Like Growth Factor II / genetics*
  • Insulin-Like Growth Factor II / metabolism
  • Kruppel-Like Transcription Factors / genetics*
  • Kruppel-Like Transcription Factors / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / etiology
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / pathology

Substances

  • Dietary Fats
  • IGF2 protein, mouse
  • Kruppel-Like Transcription Factors
  • Peg3 protein, mouse
  • Insulin-Like Growth Factor II

Grants and funding

This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Ministry of Health, Labor and Welfare of Japan; the National Institute of Biomedical Innovation; and the Takeda Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.