1. Investigación

Scope : Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and cardiovascular diseases. However, consumption of beverages containing fructose is allowed during gestation. Homocysteine (Hcy) is a well-known risk factor for cardiovascular diseases while hydrogen sulfide (H2S), a product of its metabolism, has been proved to exert opposite effects to Hcy. Methods and results : First, we investigated whether maternal fructose intake produces subsequent changes in Hcy metabolism and H2S synthesis of the progeny. Carbohydrates were supplied to pregnant rats in drinking water (10% wt/vol) throughout gestation. Adult female descendants from fructosefed, control or glucose-fed mothers were studied. Females from fructose-fed mothers had elevated homocysteinemia, hepatic H2S production, cystathionine -lyase (CSE) (the key enzyme in H2S synthesis) expression and plasma H2S, versus the other two groups. Second, we studied how adult female progeny from control (C/F), fructose- (F/F) and glucose-fed (G/F) mothers responded to liquid fructose and compared them to the control group (C/C). Interestingly, both hepatic CSE expression and H2S synthesis were diminished by fructose intake, this effect being more pronounced in F/F females. Conclusions : Maternal fructose intake produces a fetal programming that increases hepatic H2S production and, in contrast, exacerbates its fructose-induced drop in female progeny.

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 versus 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 LXR target genes related to lipogenesis paralleled to that for LXR expression. In accordance with this, LXR 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 LXR epigenetically, and both hepatic mRNA gene expression and plasma parameters of cholesterol metabolism in adult progeny. Changes in the LXR promoter methylation might be related to the availability of the methyl donor folate.