Maternal Fructose Research Articles

Cardiac Hypertrophy in Pregnant Rats, Descendants of Fructose-Fed Mothers, an Effect That Worsens with Fructose Supplementation.

The role of fructose consumption in the development of obesity, MetS, and CVD epidemic has been widely documented. Notably, among other effects, fructose consumption has been demonstrated to induce cardiac hypertrophy. Moreover, fructose intake during pregnancy can cause hypertrophy of the maternal heart. Our previous research has demonstrated that maternal fructose intake has detrimental effects on fetuses, which persist into adulthood and are exacerbated upon re-exposure to fructose. Additionally, we found that maternal fructose consumption produces changes in female progeny that alter their own pregnancy. Despite these findings, fructose intake during pregnancy is not currently discouraged. Given that cardiac hypertrophy is a prognostic marker for heart disease and heart failure, this study aimed to determine whether metabolic changes occurring during pregnancy in the female progeny of fructose-fed mothers could provoke a hypertrophic heart. To test this hypothesis, pregnant rats from fructose-fed mothers, with (FF) and without (FC) fructose supplementation, were studied and compared to pregnant control rats (CC). Maternal hearts were analyzed. Although both FF and FC mothers exhibited heart hypertrophy compared to CC rats, cardiac DNA content was more diminished in the hearts of FF dams than in those of FC rats, suggesting a lower number of heart cells. Accordingly, changes associated with cardiac hypertrophy, such as HIF1α activation and hyperosmolality, were observed in both the FC and FF dams. However, FF dams also exhibited higher oxidative stress, lower autophagy, and decreased glutamine protection against hypertrophy than CC dams. In conclusion, maternal fructose intake induces changes in female progeny that alter their own pregnancy, leading to cardiac hypertrophy, which is further exacerbated by subsequent fructose intake.

Consumption of a western diet affects thyroid hormone metabolism and signaling: A dependent effect of maternal fructose intake

Consumption of a western diet affects thyroid hormone metabolism and signaling: A dependent effect of maternal fructose intake

Fructose Consumption Affects Placental Production of H2S: Impact on Preeclampsia-Related Parameters.

H2S, a gasotransmitter that can be produced both via the transsulfuration pathway and non-enzymatically, plays a key role in vasodilation and angiogenesis during pregnancy. In fact, the involvement of H2S production on plasma levels of sFLT1, PGF, and other molecules related to preeclampsia has been demonstrated. Interestingly, we have found that maternal fructose intake (a common component of the Western diet) affects tissular H2S production. However, its consumption is allowed during pregnancy. Thus, (1) to study whether maternal fructose intake affects placental production of H2S in the offspring, when pregnant; and (2) to study if fructose consumption during pregnancy can increase the risk of preeclampsia, pregnant rats from fructose-fed mothers (10% w/v) subjected (FF) or not (FC) to a fructose supplementation were studied and compared to pregnant control rats (CC). Placental gene expression, H2S production, plasma sFLT1, and PGF were determined. Descendants of fructose-fed mothers (FC) presented an increase in H2S production. However, if they consumed fructose during their own gestation (FF), this effect was reversed so that the increase disappeared. Curiously, placental synthesis of H2S was mainly non-enzymatic. Related to this, placental expression of Cys dioxygenase, an enzyme involved in Cys catabolism (a molecule required for non-enzymatic H2S synthesis), was significantly decreased in FC rats. Related to preeclampsia, gene expression of sFLT1 (a molecule with antiangiogenic properties) was augmented in both FF and FC dams, although these differences were not reflected in their plasma levels. Furthermore, placental expression of PGF (a molecule with angiogenic properties) was decreased in both FC and FF dams, becoming significantly diminished in plasma of FC versus control dams. Both fructose consumption and maternal fructose intake induce changes in molecules that contribute to increasing the risk of preeclampsia, and these effects are not always mediated by changes in H2S production.

Maternal fructose intake aggravates the harmful effects of a Western diet in rat male descendants impacting their cholesterol metabolism.

Scope: fructose consumption from added sugars correlates with the epidemic rise in MetS and CVD. Maternal fructose intake has been described to program metabolic diseases in progeny. However, consumption of fructose-containing beverages is allowed during gestation. Cholesterol is also a well-known risk factor for CVD. Therefore, it is essential to study Western diets which combine fructose and cholesterol and how maternal fructose can influence the response of progeny to these diets. Methods and results: a high-cholesterol (2%) diet combined with liquid fructose (10%), as a model of an unhealthy Western diet, was administered to descendants from control and fructose-fed mothers. Gene (mRNA and protein) expression and plasma, fecal and tissue parameters of cholesterol metabolism were measured. Interestingly, progeny from fructose-fed dams consumed less liquid fructose and cholesterol-rich chow than males from control mothers. Moreover, descendants of fructose-fed mothers fed a Western diet showed an increased cholesterol elimination through bile and feces than males from control mothers. Despite these mitigating circumstances to develop a proatherogenic profile, the same degree of hypercholesterolemia and severity of steatosis were observed in all descendants fed a Western diet, independently of maternal intake. An increased intestinal absorption of cholesterol, synthesis, esterification, and assembly into lipoprotein found in males from fructose-fed dams consuming a Western diet could be the cause. Moreover, an augmented GLP2 signalling seen in these animals would explain this enhanced lipid absorption. Conclusions: maternal fructose intake, through a fetal programming, makes a Western diet considerably more harmful in their descendants than in the offspring from control mothers.

Impact of maternal fructose intake on liver stem/progenitor cells in offspring: Insights into developmental origins of health and disease

AimsThe developmental origin of health and disease (DOHaD) theory postulates that poor nutrition during fetal life increases the risk of disease later in life. Excessive fructose intake has been associated with obesity, diabetes, and nonalcoholic fatty liver disease, and maternal fructose intake during pregnancy has been shown to affect offspring health. In this study, we investigated the effects of high maternal fructose intake on the liver stem/progenitor cells of offspring. Main methodA fructose-based DOHaD model was established using Sprague-Dawley rats. Small hepatocytes (SHs), which play an important role in liver development and regeneration, were isolated from the offspring of dams that were fed a high-fructose corn syrup (HFCS) diet. The gene expression and DNA methylation patterns were analyzed on postnatal day (PD) 21 and 60. Key findingsMaternal HFCS intake did not affect body weight or caloric intake, but differences in gene expression and DNA methylation patterns were observed in the SHs of offspring. Functional analysis revealed an association between metabolic processes and ion transport. SignificanceThese results suggest that maternal fructose intake affects DNA methylation and gene expression in the liver stem/progenitor cells of offspring. Furthermore, the prolonged retention of these changes in gene expression and DNA methylation in adulthood (PD 60) suggests that maternal fructose intake may exert lifelong effects. These findings provide insights into the DOHaD for liver-related disorders and highlight the importance of maternal nutrition for the health of the next generation.

Transcriptome analysis of the effects of maternal fructose exposure during gestation and lactation on the cytoskeleton of offspring hippocampus

Excessive fructose consumption poses a public health concern. Maternal fructose overconsumption impairs offspring hippocampal function, indicating hippocampal sensitivity to fructose. The hippocampus is the vital for spatial learning and memory, and the cytoskeletal structure is crucial for hippocampal neuronal plasticity. The Rho GTPase is a key regulator of neuronal cytoskeleton formation, with RhoA protein governing neuronal growth and development. The RhoA/ROCK2 pathway affects myosin light chain phosphorylation, leading to cytoskeletal reorganization, actin cytoskeleton changes, and neurite retraction. However, the effects of maternal fructose exposure during gestation and lactation on the offspring's neural cytoskeleton remain unclear. We established maternal fructose exposure models during gestation and lactation, assessing fasting blood glucose levels in offspring confirm model effectiveness. Whole transcriptome sequencing examined offspring hippocampal developmental programming. Immunofluorescence and Western blot analyses assessed RhoA/ROCK2 pathway expression changes in the hippocampus, with PCR validating transcriptome sequencing results. Transcriptome sequencing identified 193 and 298 differentially expressed genes in the control, 13% fructose, and 40% fructose groups, respectively. GO and KEGG analyses revealed significant changes related to neural development, learning memory, and cytoskeleton in both fructose-exposed groups. GSEA indicated substantial cytoskeleton-related alterations in the offspring. Immunofluorescence demonstrated significant CRMP2 protein down-regulation in both fructose-exposed groups. Western blotting showed significantly higher expression of RhoA, ROCK2, p-ROCK2, and p-MLC2 in the fructose-exposed groups (P < 0.05). Maternal high-fructose exposure significantly impacts gene expression in offspring. These alterations may influence hippocampal neurodevelopment by up-regulating the RhoA/ROCK2 pathway, leading to cytoskeletal damage and axon growth inhibition.

Lipid peroxidation and neuroinflammation: A possible link between maternal fructose intake and delay of acquisition of neonatal reflexes in Wistar female rats.

Fructose is a common sweetener found in the daily diet supplemented to many processed and ultra-processed foods and beverages. Consumption of fructose-sweetened beverages has drastically increased in the last decades and is widely associated with metabolic disease, systemic pro-inflammatory status, and adverse transgenerational effects. To date, the impact of maternal fructose intake in brain function of the offspring is less explored. Therefore, the aim of this study was first, to investigate adverse effects in developmental milestones of the progeny of mothers with metabolic syndrome (MetS), induced by ad libitum consumption of a 20% fructose solution, and second to identify possible molecular changes in the nervous system of the newborns associated with maternal fructose intake. Wistar rats were randomly separated into two groups with access to water or fructose (20% w/v in water) for 10 weeks. After MetS was confirmed, dams were mated with control males and continued drinking water or fructose solution during gestation. At postnatal day (PN) 1, a subgroup of offspring of each sex was sacrificed and brains were dissected for oxidative stress and inflammatory status analysis. Changes in the developmental milestones due to maternal fructose consumption were studied (PN3-PN21) in another subgroup of offspring. Sexually dimorphic effects were found on the progeny's acquisition of neurodevelopmental milestones, in brain lipid peroxidation, neuroinflammation, and antioxidative defensive response. Our results suggest that dams' MetS, induced by fructose intake, disrupts brain redox homeostasis in female offspring and affects sensorimotor brain circuitry which may have a translational value for studying neurodevelopmental diseases.

Maternal Intake of Either Fructose or the Artificial Sweetener Acesulfame-K Results in Differential and Sex-Specific Alterations in Markers of Skin Inflammation and Wound Healing Responsiveness in Mouse Offspring: A Pilot Study.

Growing evidence has demonstrated that maternal artificial sweetener (AS) consumption may not be a beneficial alternative when compared to sugar-sweetened beverages and potentially leads to metabolic dysfunction in adult offspring. Compromised skin integrity and wound healing associated with type 2 diabetes can lead to complications such as diabetic pressure injury (PI). In this context, the skin plays an important role in the maintenance of metabolic homeostasis, yet there is limited information on the influence of sugar- or AS-sweetened beverages during pregnancy on developmental programming and offspring skin homeostasis. This study examined the impact of maternal fructose or acesulfame-k consumption on offspring wound healing. Female C57Bl/6 mice received a chow diet ad libitum with either water (CD), fructose (FR; 34.7 mM fructose), or AS (AS; 12.5 mM Acesulfame-K) throughout pregnancy and lactation. PIs were induced in offspring at 9 weeks of age (n = 6/sex/diet). PIs and healthy skin biopsies were collected for later analysis. Maternal AS intake increased skin inflammatory markers in healthy biopsies while an FR diet increased Tgfb expression, and both diets induced subtle changes in inflammatory markers post-wound inducement in a sex-specific manner. Furthermore, a maternal FR diet had a significant effect on pressure wound severity and early wound healing delay, while AS maternal diet had a sex-specific effect on the course of the healing process. This study demonstrates the need for a better understanding of developmental programming as a mediator of later-life skin integrity and wound responsiveness.

Transcriptomic evidence of hypothalamus for maternal fructose exposure induced offspring hypertension through AT1R/TLR4 pathway

Maternal fructose exposure during pregnancy and lactation has been shown to contribute to hypertension in offspring, with long-term effects on hypothalamus development. However, the underlying mechanisms remain unclear. In this study, we used the tail-cuff method to evaluate the effects of maternal fructose drinking exposure on offspring blood pressure levels at postpartum day 21 (PND21) and postpartum day 60 (PND60). We employed Oxford Nanopore Technologies (ONT) full-length RNA sequencing to investigate the developmental programming of the PND60 offspring's hypothalamus and confirmed the presence of the AT1R/TLR4 pathway using western blot and immunofluorescence. Our findings demonstrated that maternal fructose exposure significantly increased blood pressure in PND60 offspring but not in PND21 offspring. Additionally, we observed transcriptome-wide alterations in the hypothalamus of PND60 offspring following maternal fructose exposure. Overall, our study provides evidence that maternal fructose exposure during pregnancy and lactation may alter the transcriptome-wide of offspring hypothalamus and activate the AT1R/TLR4 pathway, leading to hypertension. These findings may have important implications for the prevention and treatment of hypertension-related diseases in offspring exposed to excessive fructose during pregnancy and lactation.

Alternative splicing affects synapses in the hippocampus of offspring after maternal fructose exposure during gestation and lactation

Increased fructose over-intake is a global issue. Maternal fructose exposure during gestation and lactation can impair brain development in offspring. However, the effect on synapses is still unknown. For the diversification of RNA and biological functions, alternative splicing (AS) and alternative polyadenylation (APA) are essential. We constructed a maternal high-fructose diet model by administering 13% and 40% fructose water. The student's t-test analyzed the results of RT-qPCR. All other results were analyzed by one-way analysis of variance. The animal behavior experiment results revealed that conditioning and associative memory had been damaged. The proteins that form synapses were consistently low-expressed. In addition, compared with the control group, the Oxford Nanopore Technologies platform's full-length RNA-sequencing identified 298 different spliced genes (DSGs) and 51 differentially expressed alternative splicing (DEAS) genes in the 13% fructose group. 313 DSGs and 74 DEAS genes were in the 40% fructose group. Enrichment analysis based on these altered genes revealed some enlightening items and pathways. Our findings demonstrated the transcriptome mechanism underlying maternal fructose exposure during gestation and lactation and impaired synapse function during the transcripts' editing.

Maternal High-Fructose Corn Syrup Intake Impairs Corticosterone Clearance by Reducing Renal 11β-Hsd2 Activity via miR-27a-Mediated Mechanism in Rat Offspring.

We previously reported that maternal fructose consumption increases blood corticosterone levels in rat offspring. However, the underlying mechanism of action remains unclear. In the present study, we aimed to elucidate the molecular mechanism by which maternal high-fructose corn syrup (HFCS) intake increases circulating GC levels in rat offspring (GC; corticosterone in rodents and cortisol in humans). Female Sprague Dawley rats received HFCS solution during gestation and lactation. The male offspring were fed distilled water from weaning to 60 days of age. We investigated the activities of GC-metabolizing enzymes (11β-Hsd1 and 11β-Hsd2) in various tissues (i.e., liver, kidney, adrenal glands, muscle, and white adipose tissue) and epigenetic modification. 11β-Hsd2 activity decreased in the kidney of the HFCS-fed dams. Moreover, the epigenetic analysis suggested that miR-27a reduced Hsd11b2 mRNA expression in the kidney of offspring. Maternal HFCS-induced elevation of circulating GC levels in offspring may be explained by a decrease in 11β-Hsd2 activity via renal miR-27a expression. The present study may allow us to determine one of the mechanisms of GC elevation in rat offspring that is often observed in the developmental origins of the health and disease (DOHaD) phenomenon.

Reprogramming Effects of Postbiotic Butyrate and Propionate on Maternal High-Fructose Diet-Induced Offspring Hypertension.

Maternal nutrition has a key role in the developmental programming of adult disease. Excessive maternal fructose intake contributes to offspring hypertension. Newly discovered evidence supports the idea that early-life gut microbiota are connected to hypertension later in life. Short-chain fatty acids (SCFAs), butyrate, and propionate are microbiota-derived metabolites, also known as postbiotics. The present study aimed to determine whether maternal butyrate or propionate supplementation can protect offspring from hypertension using a maternal high-fructose (HF) diet rat model. Female Sprague Dawley rats were allocated during pregnancy and lactation to (1) regular chow (ND); (2) 60% high-fructose diet (HF); (3) HF diet plus butyrate (HFB, 400 mg/kg/day); and (4) HF diet plus propionate (HFP, 200 mmol/L). Male offspring were sacrificed at 12 weeks of age. The maternal HF diet impaired the offspring's BP, which was prevented by perinatal butyrate or propionate supplementation. Both butyrate and propionate treatments similarly increased plasma concentrations of propionic acid, isobutyric acid, and valeric acid in adult offspring. Butyrate supplementation had a more profound impact on trimethylamine N-oxide metabolism and nitric oxide parameters. Whilst propionate treatment mainly influenced gut microbiota composition, it directly altered the abundance of genera Anaerovorax, Lactobacillus, Macellibacteroides, and Rothia. Our results shed new light on targeting gut microbiota through the use of postbiotics to prevent maternal HF intake-primed hypertension, a finding worthy of clinical translation.

Maternal fructose boosts the effects of a Western-type diet increasing SARS-COV-2 cell entry factors in male offspring.

Fructose-rich beverages and foods consumption correlates with the epidemic rise in cardiovascular disease, diabetes and obesity. Severity of COVID-19 has been related to these metabolic diseases. Fructose-rich foods could place people at an increased risk for severe COVID-19. We investigated whether maternal fructose intake in offspring affects hepatic and ileal gene expression of proteins that permit SARS-CoV2 entry to the cell. Carbohydrates were supplied to pregnant rats in drinking water. Adult and young male descendants subjected to water, liquid fructose alone or as a part of a Western diet, were studied. Maternal fructose reduced hepatic SARS-CoV2 entry factors expression in older offspring. On the contrary, maternal fructose boosted the Western diet-induced increase in viral entry factors expression in ileum of young descendants. Maternal fructose intake produced a fetal programming that increases hepatic viral protection and, in contrast, exacerbates fructose plus cholesterol-induced diminution in SARS-CoV2 protection in small intestine of progeny.

Learning and memory impairment and transcriptomic profile in hippocampus of offspring after maternal fructose exposure during gestation and lactation.

Increased fructose intake is a global issue, especially in mothers. Maternal fructose exposure during gestation and lactation can affect learning and memory in offspring; however, the detailed mechanism is still unknown. The hippocampus is a mind locale liable for learning and memory. Here, we established a maternal high-fructose diet model by administering 13% and 40% fructose water, applied the Morris Water Maze test on postnatal day 60 offspring, and performed full-length RNA sequencing using the Oxford Nanopore Technologies platform to explore the changes in gene expression in the hippocampus. The results showed that learning and memory in offspring were negatively affected. Compared with the control group, 369 differentially expressed transcripts (DETs) were identified in the 13% fructose group, and 501 DETs were identified in the 40% fructose group. Gene Ontology enriched term and Kyoto Encyclopedia of Genes and Genomes enriched pathway analyses identified several terms and pathways related to brain development and cognitive function. Furthermore, we confirmed that the Wnt/β-catenin signaling pathway was down-regulated and neuron degeneration was enhanced. In summary, our results indicate that maternal fructose exposure during gestation and lactation can impair learning and memory in offspring and affect brain function at the transcriptome level.

La ingesta materna de fructosa modula el metabolismo del colesterol en respuesta a una dieta occidental en la descendencia

Fructose consumption has increased during the last decades, while a simultaneous rise in the incidence of pathologies such as type 2 diabetes and metabolic syndrome has also taken place. Although there is evidence that fructose can cause alterations in the offspring related to the development of the aforementioned diseases, exposure to fructose during pregnancy is not contraindicated for women. This effect is explained by the concept of foetal programming, which suggests that changes that occur during the embryogenic and foetal stages are permanent in the adult, due to maternal health, diet and other environmental factors. Therefore, the effect of fructose on cholesterol metabolism in the offspring of mothers fed with or without fructose during gestation was studied. In addition, the progeny also received different diets: fructose (with and without supplementation of cholesterol) or tagatose solutions. Tagatose increased non-HDL cholesterol in the offspring of water-fed mothers, whereas fructose consumption during gestation dampened this effect, indicating foetal programming. In addition, fructose and tagatose feeding increased atherogenic indices by decreasing HDL-cholesterol concentration and increasing triglycerides levels. On the other hand, the addition of cholesterol to fructose consumption caused an increase in total cholesterol and a change in its distribution: higher concentration of non-HDL cholesterol and lower concentration of HDL cholesterol, independently of maternal feeding. This also caused an increase in atherogenic indices. Ultimately, the results indicate that cholesterol metabolism is influenced by both maternal fructose consumption, and the subsequent intake of fructose (alone or in combination with cholesterol) and tagatose in the offspring.

Effects of maternal fructose intake on the offspring's kidneys.

Fructose overload is associated with cardiovascular and metabolic disorders. During pregnancy, these alterations may affect the maternal environment and predispose offspring to diseases. Aims: To evaluate the renal morphology and function of offspring of dams that received fructose overload during pregnancy and lactation. Methods: Female Wistar rats were divided into the control (C) and fructose (F) groups. C received food and water ad libitum, and F received food and d-fructose solution (20%) ad libitum. The d-fructose offer started 1 week before mating and continued during pregnancy and lactation. The progeny were designated as control (C) or fructose (F); after weaning, half of the F received water to drink (FW), and half received d-fructose (FF). Blood pressure (BP) and renal function were evaluated. The expression of sodium transporters (NHE3-exchanger, NKCC2 and NCC-cotransporters, and ENaC channels) and markers of renal dysfunction, including ED1 (macrophage), eNOS, 8OHdG (oxidative stress), renin, and ACE 1 and 2, were evaluated. CEUA-UNIFESP: 2757270117. The FF group presented with reduced glomerular filtration rate and urinary osmolarity, increased BP, proteinuria, glomerular hypertrophy, macrophage infiltration, and increased expression of transporters (NHE3, NCC, and ENaC), 8OHdG, renin, and ACE1. The FW group did not show increased BP and renal functional alterations; however, it presented glomerular hypertrophy, macrophage infiltration, and increased expression of the transporters (NHE3, NKCC2, NCC, and ENaC), renin, and ACE1. These data suggest that fructose overload during fetal development alters renal development, resulting in the increased expression of renin, ACE1, and sodium transporters, thus predisposing to hypertension and renal dysfunction.

Maternal fructose intake during pregnancy and lactation: Later effects on renal function.

Excessive fructose consumption has been associated with hypertension and metabolic disorders and can alter physiological adaptations during pregnancy, with long‐term detrimental consequences. This study evaluated in post‐weaning mothers the effects of increased fructose consumption during pregnancy and lactation on blood pressure and renal function. Female Wistar rats were assigned to one of four experimental groups: non‐pregnant control (NPC); pregnant control (PC); non‐pregnant fructose (NPF), and pregnant fructose (PF). Control rats had free access to food and water, while the fructose groups had free access to food and to a 20% fructose solution, over the time period of the experiment. The systolic BP and renal function parameters were measured at the end of the experimental period, one week after weaning (28 days after delivery). The results were presented as means ± standard error. Higher values of BP were observed in both pregnant and non‐pregnant rats treated with fructose compared to control. Creatinine clearance was reduced only in the PF group; however, both the PF and NPF groups had reduced Na+ and K+ excretions. In the PF group, there was also glomerular enlargement and changes in the media/lumen (M/L) ratio of interlobular arteries. Additionally, the PF group showed increased macrophage infiltration and expression of alpha‐SM‐actin and reduced expression of nitric‐oxide‐synthase endothelial in renal tissue. These findings suggest that the association of high fructose intake with pregnancy aggravated kidney changes that persisted for up to four weeks after delivery, which may represent a risk factor for maternal health.

Maternal fructose intake reinforces the effects of a Western-type diet in promoting SARS-CoV-2 cell entry factors in male offspring

Background and Aims : Fructose consumption has increased considerably, in a similar way to the prevalence of obesity, cardiovascular disease and diabetes. Further, maternal intake is a key factor involved in the development of diseases in offspring. Severity of COVID-19 has been related to the prevalence of these metabolic diseases. Therefore, fructose-rich processed foods and sugary drinks could place these patients at an increased risk for severe COVID-19. Present work studies whether maternal fructose produces in offspring changes in gene expression of molecules that permit SARS-CoV2 entry to the cell.

The Impact of Gut Microbiome on Maternal Fructose Intake-Induced Developmental Programming of Adult Disease.

Excessive or insufficient maternal nutrition can influence fetal development and the susceptibility of offspring to adult disease. As eating a fructose-rich diet is becoming more common, the effects of maternal fructose intake on offspring health is of increasing relevance. The gut is required to process fructose, and a high-fructose diet can alter the gut microbiome, resulting in gut dysbiosis and metabolic disorders. Current evidence from animal models has revealed that maternal fructose consumption causes various components of metabolic syndrome in adult offspring, while little is known about how gut microbiome is implicated in fructose-induced developmental programming and the consequential risks for developing chronic disease in offspring. This review will first summarize the current evidence supporting the link between fructose and developmental programming of adult diseases. This will be followed by presenting how gut microbiota links to common mechanisms underlying fructose-induced developmental programming. We also provide an overview of the reprogramming effects of gut microbiota-targeted therapy on fructose-induced developmental programming and how this approach may prevent adult-onset disease. Using gut microbiota-targeted therapy to prevent maternal fructose diet-induced developmental programming, we have the potential to mitigate the global burden of fructose-related disorders.

Maternal high-fructose corn syrup consumption causes insulin resistance and hyperlipidemia in offspring via DNA methylation of the Pparα promoter region

There are concerns about the negative effects of fructose intake during pregnancy on the next generation. We have previously reported that offspring from dams fed with fructose during gestation and lactation demonstrate abnormal lipid metabolism in the liver. In this study, we aimed to elucidate the molecular mechanism of the effects of maternal high-fructose corn syrup (HFCS) consumption on offspring. Pregnant Sprague-Dawley rats were fed with 20% HFCS water solution during gestation and lactation. Offspring were put on a normal diet after weaning, and the serum parameters and gene expression patterns were studied at predetermined intervals. Offsprings from pregnant rats fed with 20% HFCS (HFCS group) developed insulin resistance and hyperlipidemia at 60 d of age. RNA-seq analysis demonstrated that peroxisome proliferator-activated receptor α (PPARα) expression is downregulated by maternal HFCS intake. Hepatic Pparα expression in the HFCS group appeared to be suppressed by the enhanced DNA methylation of its promoter region. It is suggested that the development of insulin resistance and hyperlipidemia in the HFCS group may be attributable to aberrant Pparα methylation in the offspring liver. Pparα hypermethylation may be one of molecular mechanism underlying the toxicity of maternal fructose intake.