Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9954196 | The Journal of Nutritional Biochemistry | 2018 | 40 Pages |
Abstract
Fructose consumption from added sugars correlates with the epidemic rise in obesity, metabolic syndrome and cardiovascular diseases. However, consumption of beverages containing fructose is allowed during gestation. We have investigated whether maternal fructose intake produces subsequent changes in cholesterol metabolism of progeny. Carbohydrates were supplied to pregnant rats in drinking water (10% w/v solution) throughout gestation. Adult male and female descendants from fructose-fed, control or glucose-fed mothers were studied. Male offspring from fructose-fed mothers had elevated plasma HDL-cholesterol levels, whereas female progeny from fructose-fed mothers presented lower levels of non-HDL cholesterol vs. the other two groups. Liver X-receptor (LXR), an important regulator of cholesterol metabolism, and its target genes such as scavenger receptor B1, ATP-binding cassette (ABC)G5 and cholesterol 7-alpha hydroxylase showed decreased gene expression in males from fructose-fed mothers and the opposite in the female progeny. Moreover, the expression of a number of LXRα target genes related to lipogenesis paralleled to that for LXRα expression. In accordance with this, LXRα gene promoter methylation was increased in males from fructose-fed mothers and decreased in the corresponding group of females. Surprisingly, plasma folic acid levels, an important methyl-group donor, were augmented in males from fructose-fed mothers and diminished in female offspring. Maternal fructose intake produces a fetal programming that influences, in a gender-dependent manner, the transcription factor LXRα epigenetically, and both hepatic mRNA gene expression and plasma parameters of cholesterol metabolism in adult progeny. Changes in the LXRα promoter methylation might be related to the availability of the methyl donor folate.
Keywords
ABCLXRαSCD1SREBPNtcpLRH1BSEPRCTDnmtstearoyl-CoA desaturasePPARLDLRSHPFASHDLACCCYP7A13-hydroxy-3-methylglutaryl-CoA reductaseDNA methyltransferaseHMG-CoA reductaseacetyl-CoA carboxylasefatty acid synthaseEpigeneticsPregnancyFetal programmingCpG islandssmall heterodimer partnerFructoseHigh-density lipoproteinssterol response element binding proteinBile salt export pumpcholesterolreverse cholesterol transportATP-binding cassetteLDL receptorperoxisome proliferator-activated receptorliver receptor homolog 1
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Authors
Silvia Rodrigo, Elena Fauste, Maite de la Cuesta, Lourdes RodrÃguez, Juan J. Álvarez-Millán, MarÃa I. Panadero, Paola Otero, Carlos Bocos,