Paternal allele influences high fat diet-induced obesity

Sumiyo Morita; Takuro Horii; Mika Kimura; Yuji Arai; Yasutomi Kamei; Yoshihiro Ogawa; Izuho Hatada

doi:10.1371/journal.pone.0085477

Paternal allele influences high fat diet-induced obesity

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

Authors

Sumiyo Morita¹, Takuro Horii¹, Mika Kimura¹, Yuji Arai², Yasutomi Kamei³, Yoshihiro Ogawa⁴, Izuho Hatada¹

Affiliations

¹ Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Showa-machi Maebashi, Japan.
² Division of Developmental Biotechnology, Department of Bioscience and Genetics, Research Institute, National Cerebral and Cardiovascular Center, Fujishiro-dai, Suita, Osaka, Japan.
³ Laboratory of Molecular Nutrition, Graduate School of Environmental and Life Science, Kyoto Prefectural University, Hangi-cho, Shimogamo, Sakyo-ku, Kyoto, Japan.
⁴ Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Yushima, Tokyo, Japan.

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.