Maternal Fructose Intake Induces Insulin Resistance and Oxidative Stress in Male, but Not Female, Offspring

Abstract

Objective. 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. Recently, we found that an intake of fructose (10% wt/vol) throughout gestation produces an impaired fetal leptin signalling. Therefore, we have investigated whether maternal fructose intake produces subsequent changes in their progeny. Methods. Blood samples from fed and 24 h fasted female and male 90-day-old rats born from fructose-fed, glucose-fed, or control mothers were used. Results. After fasting, HOMA-IR and ISI (estimates of insulin sensitivity) were worse in male descendents from fructose-fed mothers in comparison to the other two groups, and these findings were also accompanied by a higher leptinemia. Interestingly, plasma AOPP and uricemia (oxidative stress markers) were augmented in male rats from fructose-fed mothers compared to the animals from control or glucose-fed mothers. In contrast, female rats did not show any differences in leptinemia between the three groups. Further, insulin sensitivity was significantly improved in fasted female rats from carbohydrate-fed mothers. In addition, plasma AOPP levels tended to be diminished in female rats from carbohydrate-fed mothers. Conclusion. Maternal fructose intake induces insulin resistance, hyperleptinemia, and plasma oxidative stress in male, but not female, progeny.

Associations of maternal macronutrient intake during pregnancy with infant BMI peak characteristics and childhood BMI1–3

“…Moreover, the fetal programming of offspring metabolism and appetite might occur in an unfavorable in utero environment because of suboptimal maternal nutrition (13). In animal studies, the offspring of pregnant rats or mice that were fed a high-sugar (fructose) diet displayed a wide array of metabolic and inflammatory dysregulations including impaired leptin signaling (41), insulin resistance, plasma oxidative stress (42), and a higher expression of phosphoenolpyruvate carboxykinase (which is a key rate-controlling enzyme for gluconeogenesis, the overexpression of which is associated with impaired glucose tolerance) (43). It can be argued that higher maternal carbohydrate and sugar intake may be just a proxy of childhood carbohydrate and sugar intake because of a shared family environment and that our observations may have been confounded by postnatal exposure.…”

Fructose during pregnancy provokes fetal oxidative stress: The key role of the placental heme oxygenase-1

“…(2011) showed that a high‐fructose diet during gestation and lactation compromises hepatic antioxidant status in adult male offspring . In addition, we have also found an increase in plasma levels of protein oxidation products in male, but not female, progeny from fructose‐fed dams . However, in order to avoid all these adverse effects, placenta is supposed to protect the fetus against oxygen toxicity.…”

“…In fact, it has been proposed that uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress [8]. On the other hand, it has been demonstrated that fructose is very reactive, even more so than glucose, and is able to participate in glycosilation reactions that generate free radicals [9]. Whether or not this is due to a direct effect of fructose or an indirect one mediated by the uric acid generated during fructose-metabolism, it is widely accepted that fructose-rich syrups promote an increase of oxidative stress.…”

Metabolic syndrome and selenium in fetal programming: gender differences

“…Fructose exposure also increased glucagon and leptin serum values in lactating pups. [19][20][21]23 Se intake, retention and distribution in offspring at the end of weaning Despite the fact that F-fed pups drink slightly less milk during lactation, this milk has a similar Se content to that of control dams. As this increase is greater in male pups, it could be related to the better insulin profile found in males.…”