Liquid fructose in pregnancy exacerbates fructose-induced dyslipidemia in adult female offspring

Abstract

Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and related events. Nevertheless, consumption of beverages sweetened with fructose is not regulated in gestation. Previously, we found that maternal fructose intake produces in the progeny, when fetuses, impaired leptin signaling and hepatic steatosis and then impaired insulin signaling and hypoadiponectinemia in adult male rats. Interestingly, adult females from fructose-fed mothers did not exhibit any of these disturbances. However, we think that, actually, these animals keep a programmed phenotype hidden. Fed 240-day-old female progeny from control, fructose- and glucose-fed mothers were subjected for 3weeks to a fructose supplementation period (10% wt/vol in drinking water). Fructose intake provoked elevations in insulinemia and adiponectinemia in the female progeny independently of their maternal diet. In accordance, the hepatic mRNA levels of several insulin-responsive genes were similarly affected in the progeny after fructose intake. Interestingly, adult progeny of fructose-fed mothers displayed, in response to the fructose feeding, augmented plasma triglyceride and NEFA levels and hepatic steatosis versus the other two groups. In agreement, the expression and activity for carbohydrate response element binding protein (ChREBP), a lipogenic transcription factor, were higher after the fructose period in female descendants from fructose-fed mothers than in the other groups. Furthermore, liver fructokinase expression that has been indicated as one of those responsible for the deleterious effects of fructose ingestion was preferentially augmented in that group. Maternal fructose intake does influence the adult female offspring's response to liquid fructose and so exacerbates fructose-induced dyslipidemia and hepatic steatosis.

Maternal Fructose Intake Increases Liver H2S Synthesis but Exarcebates its Fructose‐Induced Decrease in Female Progeny

“…However, LXR and CPT1 expression (genes where different methylation levels of the promoter between females from control, fructose-and glucose-fed mothers have been already confirmed [19] ) did not show differences between the three groups. [5] Interestingly, plasma bile acids levels and liver FXR activity showed similar responses to fructose intake, with more pronounced decreases in the C/F and F/F groups, in accordance with the findings observed for other FXR target gene, CSE. [34] Possibly, a reduced amount of bile acids arriving to the liver in these groups could be maintaining FXR inactivated and, accordingly, its target genes (including CSE) with a lower expression and, therefore, a diminished production of H 2 S. We do not know the reason for the differences observed in plasma bile acids levels for C/F and F/F versus G/F group, but a possible implication of some component of the enterohepatic cycle should not be discarded, as we have previously suggested.…”

“…Moreover, although the levels of the protein carbonylation marker, methylglyoxal, were not different between the three groups, the concentration of the prooxidant molecule uric acid tended to be augmented in the F/F group (Table S2, Supporting Information), in parallel to the uricemia previously reported in these animals. [5] Finally, since ammonia (NH 3 ) is produced along with H 2 S in the transsulfuration pathway, an interaction between these two gasotransmitters has been proposed. [17] Ammonia produced in transsulfuration participates in the synthesis of urea by the liver [33] and, in accordance with the diminution of hepatic H 2 S production found here in fructose-fed rats ( Figures 4A,B), plasma urea was also reduced in fructose-fed rats ( Figure 4E), becoming significantly different for F/F and G/F groups versus control (C/C) rats.…”

Lifetime Exposure to a Constant Environment Amplifies the Impact of a Fructose-Rich Diet on Glucose Homeostasis during Pregnancy

“…These factors are seldom considered in animal models of diabetes, especially those examining the impact of exposure to an adverse maternal nutritional environment on the offspring. Although there is increasing awareness of the role of high intakes of fructose in metabolic syndrome–associated diseases, such as non-alcoholic fatty liver disease [4], coronary artery disease [5] and type II diabetes [6], and a growing body of literature covering high intakes of fructose during pregnancy [7,8,9,10], there is still a lack of longer-term rodent studies following the offspring into adulthood and pregnancy. Rodent studies have demonstrated that fructose in pregnancy can significantly reduce the weight of the placenta [11], and increase the expression of genes related to lipogenesis in the offspring liver [12].…”

Maternal fructose–induced oxidative stress occurs via Tfam and Ucp5 epigenetic regulation in offspring hippocampi

“…Recently, several studies have demonstrated adverse effects associated with maternal fructose consumption in rodents. For example, in rats, maternal fructose consumption induces metabolic disorders such as low birth weight, glucose intolerance, hypertension, and fatty liver in the offspring (10)(11)(12)(13)(14).…”