1. Investigación

La fructosa, presente en la sacarosa y el jarabe de maíz rico en fructosa, se ha relacionado con el desarrollo de diabetes, obesidad y síndrome metabólico, trastornos que han alcanzado proporciones epidémicas a nivel mundial. La nutrición materna constituye uno de los factores causales que modulan el riesgo de padecer enfermedades metabólicas en la edad adulta, mediante la “programación fetal”. En un primer estudio se evaluó la administración de fructosa a descendientes de madres-fructosa o glucosa a los 8 meses de edad. En la descendencia macho adulta el consumo de fructosa aumenta la producción de FGF21, principalmente en los descendientes de madres-fructosa, y la dieta materna determina la función de FGF21 tanto en el metabolismo lipídico como en el estrés oxidativo. En la descendencia hembra, el consumo de fructosa provoca una reducción en la producción hepática de H2S, siendo más evidente en las descendentes de madres-fructosa. En el segundo procedimiento se estudió la descendencia macho de madres control o fructosa de 3 meses de edad. La ingesta materna de fructosa influye en la absorción intestinal de ácidos biliares y triglicéridos cuando se somete a la descendencia macho al consumo de tagatosa. La asociación de fructosa y colesterol condujo a una dislipemia acusada de forma independiente de la dieta materna. Además, el consumo de fructosa provocó una reducción en la producción de H2S exclusivamente en el hígado, efecto que agravado al asociar fructosa y colesterol y que no se observó tras la administración de tagatosa. Finalmente quisimos evaluar si se producía una transmisión de generación en generación de las alteraciones metabólicas asociadas al consumo de fructosa durante la gestación. Así, la descendencia hebra preñada descendiente de madres-fructosa presentaba un fenotipo programado, presentando una alterada respuesta a insulina y leptina, dislipemia y esteatosis. Es más, estos cambios se observaban también en sus fetos.

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.