Abstract
Endoplasmic reticulum (ER) homeostasis is crucial to appropriate cell functioning, and when disturbed, a safeguard system called unfolded protein response (UPR) is activated. Fructose consumption modifies ER homeostasis and has been related to metabolic syndrome. However, fructose sweetened beverages intake is allowed during gestation. Therefore, we investigate whether maternal fructose intake affects the ER status and induces UPR. Thus, administrating liquid fructose (10% w/v) to pregnant rats partially activated the ER-stress in maternal and fetal liver and placenta. In fact, a fructose-induced increase in the levels of pIRE1 (phosphorylated inositol requiring enzyme-1) and its downstream effector, X-box binding protein-1 spliced form (XBP1s), was observed. XBP1s is a key transcription factor, however, XBP1s nuclear translocation and the expression of its target genes were reduced in the liver of the carbohydrate-fed mothers, and specifically diminished in the fetal liver and placenta in the fructose-fed mothers. These XBP1s target genes belong to the ER-associated protein degradation (ERAD) system, used to buffer ER-stress and to restore ER-homeostasis. It is known that XBP1s needs to form a complex with diverse proteins to migrate into the nucleus. Since methylglyoxal (MGO) content, a precursor of advanced glycation endproducts (AGE), was augmented in the three tissues in the fructose-fed mothers and has been related to interfere with the functioning of many proteins, the role of MGO in XBP1s migration should not be discarded. In conclusion, maternal fructose intake produces ER-stress, but without XBP1s nuclear migration. Therefore, a complete activation of UPR that would resolve ER-stress is lacking. A state of fructose-induced oxidative stress is probably involved.
Highlights
In the last few decades, the prevalence of diseases related to metabolic syndrome has increased worldwide
We have previously established that maternal fructose induces oxidative stress in fetuses and placentas [29]
Total caloric intake was similar in the three groups, the amount of total calories obtained from simple sugars was 25% for the fructose-group and 35% for the glucose-group [28,29]
Summary
In the last few decades, the prevalence of diseases related to metabolic syndrome has increased worldwide. This is why, in 2002, the World Health Organization declared obesity as an epidemic disease in the 21st century. In 2011, the United Nations declared for the first time that non-communicable diseases such as diabetes, cardiovascular events, or cancer, presented a higher prevalence than infectious diseases around the world [1]. The emergence of these disorders has been mainly promoted by the introduction of unhealthy nutritional habits and a sedentary life style [2].
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