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.

Leptin resistance in obesity: An epigenetic landscape

“…A similar effect has been demonstrated in nulliparous female rats fed a high fat diet for a long period; despite significantly higher body weight and plasma leptin levels in these rats, they had relatively low POMC mRNA expression, which was associated with hypermethylation of the POMC promoter [84]. POMC neurons in the arcuate nucleus (ARC) regulate energy homeostasis by secreting α-melanocyte-stimulating hormone (α-MSH), which is derived from a POMC precursor, in response to leptin signalling.…”

Failure to upregulate Agrp and Orexin in response to activity based anorexia in weight loss vulnerable rats characterized by passive stress coping and prenatal stress experience

“…This was unexpected since clear ABA effects on gene expression were shown, and previous studies revealed differences in this region in response to dietary modulations (Marco et al, 2014). Similarly differences in Crh expression were not related to changes in DNAm of the Crh promoter region.…”

Effect of Maternal Obesity on Foetal Growth and Metabolic Health of the Offspring

“…Moreover, the offspring of dams exposed to a high-fat diet during pregnancy maintained an adverse metabolic profile and epigenetic changes through adulthood [20]. The mechanisms linking maternal malnutrition and excessive weight in pregnancy to later-life metabolic health of the offspring are unclear.…”