Paternal allele influences high fat diet-induced obesity

• Published in: PloS one 2014-01, Vol.9 (1), p.e85477
• Main Authors: Morita, Sumiyo, Horii, Takuro, Kimura, Mika, Arai, Yuji, Kamei, Yasutomi, Ogawa, Yoshihiro, Hatada, Izuho
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - metabolism; Adipocytes - pathology; Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - pathology; Analysis; Animals; Biology; Body composition; Body fat; Crosses, Genetic; Diabetes; Diet; Diet, High-Fat; Dietary Fats - adverse effects; Endocrinology; Female; Gene expression; Gene regulation; Genes; Genetic crosses; Genomes; Genomic Imprinting; Glucose; High fat diet; Homeostasis; House mouse; Inflammation; Inheritance Patterns; Insulin resistance; Insulin-like growth factor II; Insulin-Like Growth Factor II - genetics; Insulin-Like Growth Factor II - metabolism; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Laboratories; Male; Medicine; Metabolism; Mice; Mice, Inbred C57BL; Monocyte chemoattractant protein 1; Nutrition research; Obesity; Obesity - etiology; Obesity - genetics; Obesity - metabolism; Obesity - pathology; Offspring; Peg3 protein; Physiological aspects; Progeny; Rodents; Science; Tumor necrosis factor-α; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0085477

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.