אסיף מאגר המחקר החקלאי

Overweight and CpG methylation of the Pomc promoter in offspring of high-fat-diet-fed dams are not "reprogrammed" by regular chow diet in rats

Year:

2014

Source of publication :

Authors :

Volume :

28

Co-Authors:

Marco, A., Faculty of Life Sciences, Bar Ilan University, Ramat-Gan, Israel, Gonda Brain Research Center, Bar Ilan University, Ramat-Gan, Israel
Kisliouk, T., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Tabachnik, T., Faculty of Life Sciences, Bar Ilan University, Ramat-Gan, Israel, Gonda Brain Research Center, Bar Ilan University, Ramat-Gan, Israel
Meiri, N., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Weller, A., Gonda Brain Research Center, Bar Ilan University, Ramat-Gan, Israel, Department of Psychology, Bar Ilan University, Ramat-Gan, Israel

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Abstract:

This study aimed to determine whether epigenetic malprogramming induced by high-fat diet (HFD) has an obesogenic effect on nonmated and mated female rats and their offspring. Further, it aimed to reprogram offspring's epigenetic malprogramming and phenotype by providing normal diet after weaning. Body weight (BW) was measured, and plasma and hypothalamic arcuate nuclei were collected for analysis of hormones, mRNA, and DNA CpG methylation of the promoter of Pomc, a key factor in control of food intake. In nonmated females, HFD decreased Pomc/leptin ratio by ∼38%. This finding was associated with Pomc promoter hypermethylation. While heavier during pregnancy, during lactation HFD dams showed sharper BW decrease (2.5-fold) and loss of Pomc promoter hypermethylation. Moreover, their weight loss was correlated with demethylation (r=-0.707) and with gadd45b mRNA expression levels (r=0.905). Even though offspring of HFD dams ate standard chow from weaning, they displayed increased BW, Pomc promoter hypermethylation, and vulnerability to HFD challenge (3-fold kilocalorie intake increase). These findings demonstrate a long-term effect of maternal HFD on CpG methylation of the Pomc promoter in the offspring, which was not reprogrammed by standard chow from weaning. Further, the results suggest a possible mechanism of demethylation of the Pomc promoter following pregnancy and lactation. © FASEB.

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