Sex-specific epigenetic alterations of the hypothalamic Agrp-Pomc system do not explain 'diabesity' in the offspring of high-fat diet (HFD) overfed maternal rats.
Maternal high-fat diet (HFD) overfeeding pre- and during pregnancy and lactation may 'program' a 'diabesity' predisposition in the offspring, for inconclusive reasons. Acquired alterations of the hypothalamic promoter methylation and mRNA expression of the satiety neurohormone Pomc are possibly of critical importance here. We investigated within one developmental approach, including male and female rats, the sex-specific DNA methylation pattern and corresponding mRNA expression of both Pomc and its endogenous functional antagonist Agrp in the hypothalamus of adult HFD offspring. Obesity and diabetic disturbances occurred in both male and female HFD offspring, accompanied by altered Pomc promoter methylation pattern. However, this was not related to significant Pomc mRNA expression alterations. In contrast, male-specific alterations of Agrp promoter methylation were found, even associated with reduced mRNA expression of this orexigenic/anabolic Pomc antagonist. In conclusion, acquired epigenetic alterations of the hypothalamic Agrp-Pomc system hardly explain the 'diabesity' phenotype in HFD offspring, while distinct vulnerability and functionality of Agrp promoter and related genomic regions methylation should be further investigated.
['Schellong|Karen|K|', 'Melchior|Kerstin|K|', 'Ziska|Thomas|T|', 'Henrich|Wolfgang|W|', 'Rancourt|Rebecca C|RC|', 'Plagemann|Andreas|A|']
D054369:Agouti-Related Protein D000818:Animals D001786:Blood Glucose D001823:Body Composition D019175:DNA Methylation D048909:Diabetes Complications D003920:Diabetes Mellitus D059305:Diet, High-Fat D044127:Epigenesis, Genetic D005260:Female D007031:Hypothalamus D008297:Male D039382:Maternal Nutritional Physiological Phenomena D009479:Neuropeptides D009765:Obesity D044343:Overnutrition D010641:Phenotype D011247:Pregnancy D011270:Pregnancy, Animal D011297:Prenatal Exposure Delayed Effects D011333:Pro-Opiomelanocortin D011401:Promoter Regions, Genetic D051381:Rats D017208:Rats, Wistar D012737:Sex Factors
Epigenetics Maternal high-fat diet Hypothalamic arcuate nucleus Neuropeptide expression Nutritional programming Offspring ‘diabesity’