title: 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.
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.
authors.affiliation: Faculty of Life Sciences, Gonda Brain Research Center, and asafmarco@gmail.com.
authors.forename: Asaf
authors.initials: A
authors.lastname: Marco
authors.affiliation: Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kisliouk
authors.affiliation: Faculty of Life Sciences, Gonda Brain Research Center, and.
authors.forename: Tzlil
authors.initials: T
authors.lastname: Tabachnik
authors.affiliation: Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Meiri
authors.affiliation: Gonda Brain Research Center, and Department of Psychology, Bar Ilan University, Ramat-Gan, Israel; and.
authors.forename: Aron
authors.initials: A
authors.lastname: Weller
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics; D001835:Body Weight; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D059305:Diet, High-Fat / Q000009:adverse effects*; D004435:Eating; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007774:Lactation; D020738:Leptin / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D009765:Obesity / Q000209:etiology; D050177:Overweight / Q000235:genetics*; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D043484:Proprotein Convertases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014886:Weaning; D000097642:GADD45 Proteins
chemical_list: D000943:Antigens, Differentiation; D020738:Leptin; D043484:Proprotein Convertases; D012333:RNA, Messenger; C508094:Gadd45b protein, rat; D000097642:GADD45 Proteins
keywords: epigenetics; leptin; obesity