Gestational high-fat diet impaired demethylation of Pparα and induced obesity of offspring.
Gestational and postpartum high-fat diets (HFDs) have been implicated as causes of obesity in offspring in later life. The present study aimed to investigate the effects of gestational and/or postpartum HFD on obesity in offspring. We established a mouse model of HFD exposure that included gestation, lactation and post-weaning periods. We found that gestation was the most sensitive period, as the administration of a HFD impaired lipid metabolism, especially fatty acid oxidation in both foetal and adult mice, and caused obesity in offspring. Mechanistically, the DNA hypermethylation level of the nuclear receptor, peroxisome proliferator-activated receptor-α (Pparα), and the decreased mRNA levels of ten-eleven translocation 1 (Tet1) and/or ten-eleven translocation 2 (Tet2) were detected in the livers of foetal and adult offspring from mothers given a HFD during gestation, which was also associated with low Pparα expression in hepatic cells. We speculated that the hypermethylation of Pparα resulted from the decreased Tet1/2 expression in mothers given a HFD during gestation, thereby causing lipid metabolism disorders and obesity. In conclusion, this study demonstrates that a HFD during gestation exerts long-term effects on the health of offspring via the DNA demethylation of Pparα, thereby highlighting the importance of the gestational period in regulating epigenetic mechanisms involved in metabolism.
['Pang|Haiyan|H|0000-0001-9292-3782', 'Ling|Dandan|D|', 'Cheng|Yi|Y|', 'Akbar|Rubab|R|', 'Jin|Luyang|L|', 'Ren|Jun|J|', 'Wu|Haiyan|H|', 'Chen|Bin|B|', 'Zhou|Yin|Y|', 'Zhu|Hong|H|', 'Zhou|Yuzhong|Y|', 'Huang|Hefeng|H|', 'Sheng|Jianzhong|J|']
D000818:Animals D000073398:Demethylation D059305:Diet, High-Fat D005260:Female D005865:Gestational Age D050356:Lipid Metabolism D051379:Mice D008810:Mice, Inbred C57BL D009765:Obesity D047493:PPAR alpha D011247:Pregnancy D011297:Prenatal Exposure Delayed Effects
high-fat diet obesity lipid metabolism DNA demethylation normal chow diet