Gestational high‐fat diet impaired demethylation of Pparα and induced obesity of offspring. Issue 12 (6th May 2021)

• Record Type: Journal Article
• Authors: Pang, Haiyan; Ling, Dandan; Cheng, Yi; Akbar, Rubab; Jin, Luyang; Ren, Jun; Wu, Haiyan; Chen, Bin; Zhou, Yin; Zhu, Hong; Zhou, Yuzhong; Huang, Hefeng; Sheng, Jianzhong
• Is Part Of: Journal of cellular and molecular medicine. Volume 25:Issue 12(2021)
• Page Start: 5404
• Page End: 5416
• Publication Date: 2021-05-06
• Subjects: DNA demethylation -- high‐fat diet -- lipid metabolism -- normal chow diet -- obesity; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.16551
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: 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.