RRC ID 28689
Author Morita S, Horii T, Kimura M, Arai Y, Kamei Y, Ogawa Y, Hatada I.
Title Paternal allele influences high fat diet-induced obesity.
Journal PLoS One
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.
Volume 9(1)
Pages e85477
Published 2014-1-1
DOI 10.1371/journal.pone.0085477
PII PONE-D-13-28962
PMID 24416415
PMC PMC3885714
MeSH 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
IF 2.74
Times Cited 17
Mice RBRC00213