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 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.

Liquid carbohydrate intake modifies transsulfuration pathway both in pregnant rats and in their male descendants / La ingesta de carbohidratos en forma líquida modifica la ruta de la transulfuración tanto en ratas gestantes como en su descendencia macho

Introduction: Fructose, alone or in combination with glucose, has been used as a source of added sugars to manufacture sugary drinks and processed foods. High consumption of simple sugars, mainly fructose, has been demonstrated to be one of the causes of developing metabolic diseases. Maternal nutrition is a key factor in the health of the progeny when adult. However, ingestion of fructose-containing foods is still permitted during gestation. Hydrogen sulphide (H2S) is a gasotransmitter produced in the transsulfuration pathway with proved beneficial effects to combat metabolic diseases. Methods: Carbohydrates were supplied to pregnant rats in drinking water (10% wt/vol) throughout gestation, and the pregnant rats, their foetuses, and adult male descendants were studied. Later, adult male progeny from control, fructose- and glucose-fed mothers were subjected to liquid fructose, and were compared to the control group. Liver H2S production was determined. Results: This study shows that, in pregnancy, either a fructose-rich diet per se or situations that produce an impaired insulin sensitivity such as an excessive intake of glucose, decrease hepatic and placental production of H2S. Furthermore, this effect was also observed in the liver of male offspring (both in foetal and adult stages). Interestingly, when these adult descendants were subjected to a high fructose intake, decreases in H2S synthesis in liver and adipose tissue due to this fructose intake were maternal consumption dependent. Conclusions: Given H2S is a protective agent against diseases such as diabetes, obesity, cardiovascular diseases, and metabolic syndrome, the fact that carbohydrate consumption reduces H2S synthesis both in pregnancy and in their progeny could have clear and relevant clinical implications.(AU)

Introducción: La fructosa, sola o en combinación con glucosa, se usa como fuente de azúcares añadidos para elaborar bebidas azucaradas y comidas procesadas. El elevado consumo de azúcares simples, sobre todo fructosa, se ha mostrado como una de las causas del desarrollo de enfermedades metabólicas. La nutrición materna es un factor clave en la salud de la descendencia adulta. Sin embargo, el consumo de alimentos que contienen fructosa está todavía permitido durante la gestación. El sulfuro de hidrógeno (H2S) es un gasotransmisor producido en la ruta de la transulfuración con probados beneficios para luchar contra las enfermedades metabólicas. Métodos: Los carbohidratos se suministraron a las ratas gestantes en el agua de bebida (10% p/v) a lo largo de la gestación, y se estudiaron las ratas preñadas, sus fetos y los descendientes macho adultos. Posteriormente, a la progenie macho adulta procedente de madres control, alimentadas con fructosa o bien con glucosa, se le administró fructosa líquida y se comparó con un grupo control. Se determinó la producción hepática de H2S. Resultados: Este estudio muestra cómo en la gestación, una dieta rica en fructosa per se o situaciones en las que se produce una empeorada sensibilidad a la insulina tal como un consumo excesivo de glucosa, disminuyen la producción hepática y placentaria de H2S. Más aún, este efecto también fue observado en el hígado de la descendencia macho (tanto en el estado fetal como en la edad adulta). Es destacable que, cuando esta descendencia adulta era sometida a una ingesta elevada de fructosa, las disminuciones en la síntesis de H2S en el hígado y el tejido adiposo debidas a dicho consumo eran dependientes del consumo materno...(AU)

Liquid carbohydrate intake modifies transsulfuration pathway both in pregnant rats and in their male descendants.

INTRODUCTION: Fructose, alone or in combination with glucose, has been used as a source of added sugars to manufacture sugary drinks and processed foods. High consumption of simple sugars, mainly fructose, has been demonstrated to be one of the causes of developing metabolic diseases. Maternal nutrition is a key factor in the health of the progeny when adult. However, ingestion of fructose-containing foods is still permitted during gestation. Hydrogen sulphide (H2S) is a gasotransmitter produced in the transsulfuration pathway with proved beneficial effects to combat metabolic diseases. METHODS: Carbohydrates were supplied to pregnant rats in drinking water (10% wt/vol) throughout gestation, and the pregnant rats, their foetuses, and adult male descendants were studied. Later, adult male progeny from control, fructose- and glucose-fed mothers were subjected to liquid fructose, and were compared to the control group. Liver H2S production was determined. RESULTS: This study shows that, in pregnancy, either a fructose-rich diet per se or situations that produce an impaired insulin sensitivity such as an excessive intake of glucose, decrease hepatic and placental production of H2S. Furthermore, this effect was also observed in the liver of male offspring (both in foetal and adult stages). Interestingly, when these adult descendants were subjected to a high fructose intake, decreases in H2S synthesis in liver and adipose tissue due to this fructose intake were maternal consumption dependent. CONCLUSIONS: Given H2S is a protective agent against diseases such as diabetes, obesity, cardiovascular diseases, and metabolic syndrome, the fact that carbohydrate consumption reduces H2S synthesis both in pregnancy and in their progeny could have clear and relevant clinical implications.

Measurement of Serum Testosterone in Nondiabetic Young Obese Men: Comparison of Direct Immunoassay to Liquid Chromatography-Tandem Mass Spectrometry.

Hypoandrogenemia, a frequent finding in men with obesity, is defined by low concentrations of serum testosterone. Although immunoassay (IA) is the most used method for the determination of this steroid in clinical practice, liquid chromatography-mass spectrometry (LC-MS/MS) is considered a more reliable method. In this study, we aimed to compare IA versus LC-MS/MS measurement for the diagnosis of hypoandrogenemia in a cohort of 273 nondiabetic young obese men. Mean total testosterone (TT) levels were 3.20 ± 1.24 ng/mL for IA and 3.78 ± 1.4 ng/mL for LC-MS/MS. 53.7% and 26.3% of patients were classified as presenting hypoandrogenemia with IA and LC-MS/MS, respectively. Considering LC-MS/MS as the reference method, sensitivity and specificity of IA were 91.4% (95% CI 82.3-96.8) and 61.1% (95% CI 54.0-67.8), respectively. IA presented an AUC of 0.879 (95% CI 0.83-0.928). Multivariate regression analysis indicated that sex hormone-binding globulin (SHBG) concentrations (p = 0.002) and insulin resistance (p = 0.008) were factors associated with discrepant IA values. In conclusion, the determination of TT by IA in nondiabetic young men with obesity yields lower concentrations of TT than LC-MS/MS, resulting in an equivocal increased diagnosis of hypoandrogenemia, which could lead to inaccurate diagnosis and unnecessary treatment.

Adiposity is Associated with Decreased Serum 17-Hydroxyprogesterone Levels in Non-Diabetic Obese Men Aged 18-49: A Cross-Sectional Study.

Obesity is associated with decreased circulating testosterone levels, the main male sex hormone. However, there are a number of different male sex hormones whose dynamics remain poorly understood regarding this pathology. In this regard, 17 hydroxyprogesterone (17-OH progesterone), as an important precursor of testosterone synthetized in testes and adrenal glands, could play an essential role in testosterone deficiency in male obesity. Moreover, similarly to testosterone, 17-OH progesterone could be closely associated with visceral fat distribution and metabolic dysfunction. Thus, the aim of this study was to assess serum 17-OH progesterone levels in non-diabetic obese young men and to evaluate their relationship with clinical, analytical, and anthropometric parameters. We conducted a cross-sectional study including 266 non-diabetic men with obesity (BMI ≥ 30 kg/m2) aged 18-49 years; 17-OH progesterone and total testosterone (TT) were determined by high-performance liquid chromatography mass spectrometry. 17-OH progesterone levels were significantly lower in tertile 3 of body fat percentage in comparison with tertile 1 (0.74 ng/mL vs. 0.94 ng/mL, p < 0.01; Bonferroni correction) and in comparison with tertile 2 (0.74 ng/mL vs. 0.89 ng/mL, p = 0.02; Bonferroni correction). 17-OH progesterone levels correlated negatively with weight, BMI, waist circumference, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and visceral fat, and positively with TT, free testosterone (FT), luteinizing hormone, and fat-free mass percentage. Multivariate linear-regression analysis showed that body fat percentage and HOMA-IR were inversely associated with 17-OH progesterone levels, while FT and ACTH were positively linked to circulating 17-OH progesterone levels. In conclusion, in a population of non-diabetic obese young men, 17-OH progesterone levels were inversely associated with adiposity. Body fat percentage and insulin resistance were negatively related to 17-OH progesterone levels, whereas FT and ACTH levels were positively associated with 17-OH progesterone levels.

Maternal Fructose Intake Increases Liver H2 S Synthesis but Exarcebates its Fructose-Induced Decrease in Female Progeny.

SCOPE: Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and cardiovascular diseases (CVD). However, consumption of beverages containing fructose is allowed during gestation. Homocysteine (Hcy) is a well-known risk factor for CVD while hydrogen sulfide (H2 S), a product of its metabolism, has been proved to exert opposite effects to Hcy. METHODS AND RESULTS: First, it is investigated whether maternal fructose intake produces subsequent changes in Hcy metabolism and H2 S synthesis of the progeny. Carbohydrates are supplied to pregnant rats in drinking water (10% wt/vol) throughout gestation. Adult female descendants from fructose-fed, control or glucose-fed mothers are studied. Females from fructose-fed mothers have elevated homocysteinemia, hepatic H2 S production, cystathionine γ-lyase (CSE) (the key enzyme in H2 S synthesis) expression and plasma H2 S, versus the other two groups. Second, it is 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, hepatic CSE expression and H2 S synthesis are diminished by fructose intake, this effect being more pronounced in F/F females. CONCLUSION: Maternal fructose intake produces a fetal programming that increases hepatic H2 S production and, in contrast, exacerbates its fructose-induced drop in female progeny.

Prevalence of and risk factors for erectile dysfunction in young nondiabetic obese men: results from a regional study.

Erectile dysfunction (ED), a condition closely related to cardiovascular morbidity and mortality, is frequently associated with obesity. In this study, we aimed to determine the prevalence of ED and evaluate the associated risk factors in a cohort of 254 young (18-49 years) nondiabetic obese (body mass index [BMI] ≥ 30 kg m-2) men from primary care. Erectile function (International Index of Erectile Function [IIEF-5] questionnaire), quality of life (Aging Males' Symptoms [AMS scale]), and body composition analysis (Tanita MC-180MA) were determined. Total testosterone was determined using high-performance liquid chromatography-mass spectrometry. Multivariate logistic regression analysis was used to study the factors associated with ED. ED prevalence was 42.1%. Subjects with ED presented higher BMI, waist circumference, number of components of the metabolic syndrome, AMS score, insulin resistance, and a more unfavorable body composition than those without ED. Multivariate logistic regression analysis showed that a pathological AMS score (odds ratio [OR]: 4.238, P < 0.001), degree of obesity (BMI ≥ 40 kg m-2, OR: 2.602, P = 0.005, compared with BMI 30-34.9 kg m-2), high-density lipoprotein (HDL)-cholesterol levels (OR: 0.956, P = 0.004), and age (OR: 1.047, P = 0.016) were factors independently associated with ED. In conclusion, we demonstrate that, in a primary care-based cohort of nondiabetic young obese men, ED affected >40% of subjects. A pathological AMS score, the degree of obesity, and age were positively associated with ED, while elevated HDL-cholesterol levels were inversely associated with the odds of presenting ED. Further prospective studies are needed to evaluate the long-term consequences of ED in this population.

Cross-Sectional, Primary Care-Based Study of the Prevalence of Hypoandrogenemia in Nondiabetic Young Men with Obesity.

OBJECTIVE: Obesity-associated hypoandrogenemia is increasing in parallel to the obesity epidemic. The prevalence of hypoandrogenemia in nondiabetic young men with obesity is not known. This study aimed to evaluate the prevalence of hypoandrogenemia and associated risk factors in this population. METHODS: This cross-sectional study included 266 nondiabetic men < 50 years of age with obesity who were referred from primary care. Total testosterone (high-performance liquid chromatography mass spectrometry), sex hormone-binding globulin, free testosterone (FT), luteinizing hormone (LH), high-sensitivity C-reactive protein, and homeostatic model assessment of insulin resistance were determined. Body composition and erectile function were also assessed. Hypoandrogenemia was defined as FT level < 70 pg/mL. RESULTS: Subnormal FT concentrations were found in 25.6% of participants. Hypoandrogenemia prevalence was different along the BMI continuum, being > 75% in individuals with BMI ≥ 50 kg/m2 . A multivariate regression analysis indicated that increasing BMI (P < 0.001), age (P = 0.049), and reduced LH levels (P = 0.003) were independent risk factors for hypoandrogenemia. CONCLUSIONS: In a primary care-based cohort of nondiabetic young men with obesity, hypoandrogenemia was a very prevalent finding and was directly associated with adiposity. Obesity, age, and reduced LH levels were independent risk factors associated with hypoandrogenemia. Further prospective studies are needed to evaluate the long-term consequences of hypoandrogenemia in this population.

Effects of Maternal Fructose Intake on Perinatal ER-Stress: A Defective XBP1s Nuclear Translocation Affects the ER-stress Resolution.

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.

Maternal fructose induces gender-dependent changes in both LXRα promoter methylation and cholesterol metabolism in 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 vs. 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 LXRα target genes related to lipogenesis paralleled to that for LXRα expression. In accordance with this, LXRα 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 LXRα epigenetically, and both hepatic mRNA gene expression and plasma parameters of cholesterol metabolism in adult progeny. Changes in the LXRα promoter methylation might be related to the availability of the methyl donor folate.

A Proof-of-Concept of Label-Free Biosensing System for Food Allergy Diagnostics in Biophotonic Sensing Cells: Performance Comparison with ImmunoCAP.

Food allergy is a common disease worldwide with over 6% of the population (200⁻250 million people) suffering from any food allergy nowadays. The most dramatic increase seems to be happening in children and young people. Therefore, improvements in the diagnosis efficiency of these diseases are needed. Immunoglobulin type E (IgE) biomarker determination in human serum is a typical in vitro test for allergy identification. In this work, we used a novel biosensor based on label-free photonic transducers called BICELLs (Biophotonic Sensing Cells) for IgE detection. These BICELLs have a thin film of nitrocellulose over the sensing surface, they can be vertical optically interrogated, and are suitable for being integrated on a chip. The BICELLs sensing surface sizes used were 100 and 800 µm in diameter. We obtained calibration curves with IgE standards by immobilizating anti-IgE antibodies and identified with standard IgE calibrators in minute sample amounts (3 µL). The results, in similar assay format, were compared with commercially available ImmunoCAP®. The versatility of the interferometric nitrocellulose-based sensing surface was demonstrated since the limit of detections for BICELLs and ImmunoCAP® were 0.7 and 0.35 kU/L, respectively.

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

SCOPE: One of the features of metabolic syndrome caused by liquid fructose intake is an impairment of redox status. We have investigated whether maternal fructose ingestion modifies the redox status in pregnant rats and their fetuses. METHODS AND RESULTS: Fructose (10% wt/vol) in the drinking water of rats throughout gestation, leads to maternal hepatic oxidative stress. However, this change was also observed in glucose-fed rats and, in fact, both carbohydrates produced a decrease in antioxidant enzyme activity. Surprisingly, mothers fed carbohydrates displayed low plasma lipid oxidation. In contrast, fetuses from fructose-fed mothers showed elevated levels of plasma lipoperoxides versus fetuses from control or glucose-fed mothers. Interestingly, a clearly augmented oxidative stress was observed in placenta of fructose-fed mothers, accompanied by a lower expression of the transcription factor Nuclear factor-erythroid 2-related factor-2 (Nrf2) and its target gene, heme oxygenase-1 (HO-1), a potent antioxidant molecule. Moreover, histone deacetylase 3 (HDAC3) that has been proposed to upregulate HO-1 expression by stabilizing Nrf2, exhibited a diminished expression in placenta of fructose-supplemented mothers. CONCLUSIONS: Maternal fructose intake provoked an imbalanced redox status in placenta and a clear diminution of HO-1 expression, which could be responsible for the augmented oxidative stress found in their fetuses.

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

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.

Fructose only in pregnancy provokes hyperinsulinemia, hypoadiponectinemia, and impaired insulin signaling in adult male, but not female, progeny.

PURPOSE: 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 impaired fetal leptin signaling and hepatic steatosis. Therefore, we have investigated whether fructose intake during pregnancy produces subsequent changes in the progeny, when adult. METHODS: Fed 261-day-old male and female descendants from fructose-fed, control or glucose-fed mothers were used. Plasma was used to analyze glucose, insulin, leptin, and adiponectin. Hepatic expression of proteins related to insulin signaling was determined. RESULTS: Fructose intake throughout pregnancy did not produce alterations in the body weight of the progeny. Adult male progeny of fructose-fed mothers had elevated levels of insulin without a parallel increase in phosphorylation of protein kinase B. However, they displayed an augmented serine phosphorylation of insulin receptor substrate-2, indicating reduced insulin signal transduction. In agreement, adiponectin levels, which have been positively related to insulin sensitivity, were lower in male descendants from fructose-fed mothers than in the other two groups. Furthermore, mRNA levels for insulin-responsive genes were not affected (phosphoenolpyruvate carboxykinase, glucose-6-phosphatase) or they were decreased (sterol response element-binding protein-1c) in the livers of male progeny from fructose-supplemented rats. On the contrary, adult female rats from fructose-fed mothers did not exhibit any of these disturbances. CONCLUSION: Maternal fructose, but not glucose, intake confined to the prenatal stage provokes impaired insulin signal transduction, hyperinsulinemia, and hypoadiponectinemia in adult male, but not female, progeny.

Maternal fructose intake induces insulin resistance and oxidative stress in male, but not female, offspring.

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.

Fructose during pregnancy affects maternal and fetal leptin signaling.

Fructose intake from added sugars correlates with the epidemic rise in obesity, metabolic syndrome and cardiovascular diseases. Fructose intake also causes features of metabolic syndrome in laboratory animals. Therefore, we have investigated whether fructose modifies lipidemia in pregnant rats and produces changes in their fetuses. Thus, fructose administration (10% wt/vol.) in the drinking water of rats throughout gestation leads to maternal hypertriglyceridemia. This change was not observed in glucose-fed rats, although both carbohydrates produced similar changes in liver triglycerides and in the expression of transcription factors and enzymes involved in lipogenesis. After fasting overnight, mothers fed with carbohydrates were found to be hyperleptinemic. However, after a bolus of glucose, leptinemia in fructose-fed mothers showed no response, whereas it increased in parallel in glucose-fed and control mothers. Fetuses from fructose-fed mothers showed hypotriglyceridemia and a higher hepatic triglyceride content than fetuses from control or glucose-fed mothers. A higher expression of genes related to lipogenesis and a lower expression of fatty acid catabolism genes were also found in fetuses from fructose-fed mothers. Moreover, although hyperleptinemic, these fetuses exhibited increased tyrosine phosphorylation of the signal transducer and activator of transcription-3 (STAT-3) protein, without a parallel increase in the serine phosphorylation of STAT-3 nor in the suppressor of cytokine signaling-3 protein levels whose expression is regulated by leptin through STAT-3 activation. Thus, fructose intake during gestation provoked a diminished maternal leptin response to fasting and refeeding and an impairment in the transduction of the leptin signal in the fetuses, which could be responsible for their hepatic steatosis.