title: Paternal allele influences high fat diet-induced obesity.
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.
authors.affiliation: Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Showa-machi Maebashi, Japan.
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Morita
authors.affiliation: Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Showa-machi Maebashi, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Horii
authors.affiliation: Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Showa-machi Maebashi, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Division of Developmental Biotechnology, Department of Bioscience and Genetics, Research Institute, National Cerebral and Cardiovascular Center, Fujishiro-dai, Suita, Osaka, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Laboratory of Molecular Nutrition, Graduate School of Environmental and Life Science, Kyoto Prefectural University, Hangi-cho, Shimogamo, Sakyo-ku, Kyoto, Japan.
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Kamei
authors.affiliation: Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Yushima, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Showa-machi Maebashi, Japan.
authors.forename: Izuho
authors.initials: I
authors.lastname: Hatada
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D003433:Crosses, Genetic; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000009:adverse effects; D005260:Female; D018392:Genomic Imprinting; D040582:Inheritance Patterns; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D004041:Dietary Fats; C513121:IGF2 protein, mouse; D051741:Kruppel-Like Transcription Factors; C097901:Peg3 protein, mouse; D007335:Insulin-Like Growth Factor II