RESUMO
Concerns about the negative intergenerational effects of excessive fructose intake are being raised, with evidence suggesting that prenatal fructose intake increases susceptibility to metabolic and cognitive dysfunction later in life. In the present study, we hypothesized that prenatal and postnatal fructose intake acts synergistically to impact on hippocampus of adult offspring. Female Sprague-Dawley rats received distilled water or 20% high-fructose corn syrup (HFCS) solution in addition to standard chow throughout gestation and lactation. Male offspring were weaned at postnatal day 21 (PD21) and were randomized to receive distilled water or 20% HFCS solution until PD60. The following experimental groups were: CC: distilled water dams and post-weaning distilled water, CH: distilled water dams and post-weaning HFCS solution, HC: HFCS solution dams and post-weaning distilled water and HH: HFCS solution dams and post-weaning HFCS solution. The synergistic effect of maternal and post-weaning HFCS intake on the hippocampus was investigated by studying the expression of pro-inflammatory cytokine genes (Tnfa, Il1b, and Il6). At weaning, expression levels of pro-inflammatory cytokines between the offspring of the distilled water and HFCS solution fed dams were not significantly different. At PD60, Tnfa expression was significantly higher in the HH group than in the CC, HC and CH groups, whereas no significant differences were found between the CC, HC, and CH groups. These results suggest that postnatal fructose intake negatively impacts the hippocampus by acting synergistically with prenatal fructose intake.
Assuntos
Xarope de Milho Rico em Frutose , Zea mays , Animais , Feminino , Masculino , Gravidez , Ratos , Frutose/efeitos adversos , Expressão Gênica , Xarope de Milho Rico em Frutose/efeitos adversos , Hipocampo , Ratos Sprague-Dawley , ÁguaRESUMO
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.
Assuntos
Xarope de Milho Rico em Frutose , Hiperlipidemias , Resistência à Insulina , Doenças Metabólicas , Animais , Metilação de DNA , Feminino , Frutose/efeitos adversos , Xarope de Milho Rico em Frutose/efeitos adversos , Hiperlipidemias/genética , Resistência à Insulina/genética , Doenças Metabólicas/genética , PPAR alfa/genética , Gravidez , Regiões Promotoras Genéticas , Ratos , Ratos Sprague-Dawley , Zea maysRESUMO
Fructose consumption is rising globally, but maternal high fructose intake might adversely affect offspring. Our previous report demonstrated that excess maternal fructose intake impairs hippocampal function in offspring, indicating that the hippocampi of offspring are highly sensitive to maternal fructose. Here, we examined the effect of maternal high fructose on mitochondrial physiology and uncoupling protein (UCP) expression. Rat dams received a 20% fructose solution during gestation and lactation. Immediately after weaning, offspring hippocampi were isolated. Maternal high fructose consumption attenuated the mitochondrial O2 consumption rate and stimulated lipid hydroperoxide production in the hippocampi of offspring. Reduced Ucp5 and mitochondrial transcription factor A (Tfam) mRNA levels were also observed after maternal exposure to fructose. We assessed the promoter regions of both genes and found that this treatment enhanced DNA methylation levels. In addition, luciferase assays showed that this DNA methylation could reduce the transcription of both genes. Chromatin immunoprecipitation analysis demonstrated that specificity protein 1 binding to the Ucp5 promoter regions was reduced by DNA methylation. In addition, Ucp5 knockdown induced the up-regulation of reactive oxygen species levels in a rat brain glioma cell line, whereas reduced O2 consumption was observed with Tfam knockdown. Maternal high fructose intake thus induces reduced O2 oxygen consumption and increases oxidative stress in offspring, at least partly through epigenetic mechanisms involving Ucp5 and Tfam.-Yamada, H., Munetsuna, E., Yamazaki, M., Mizuno, G., Sadamoto, N., Ando, Y., Fujii, R., Shiogama, K., Ishikawa, H., Suzuki, K., Shimono, Y., Ohashi, K., Hashimoto, S. Maternal fructose-induced oxidative stress occurs viaTfam and Ucp5 epigenetic regulation in offspring hippocampi.
Assuntos
Epigênese Genética/genética , Frutose/genética , Hipocampo/fisiologia , Proteínas de Desacoplamento Mitocondrial/genética , Proteínas do Tecido Nervoso/genética , Estresse Oxidativo/genética , Efeitos Tardios da Exposição Pré-Natal/genética , Fatores de Transcrição/genética , Animais , Linhagem Celular Tumoral , Metilação de DNA/genética , Feminino , Glioma/genética , Lactação/genética , Masculino , Exposição Materna , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Gravidez , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Regulação para Cima/genética , DesmameRESUMO
Global fructose consumption is on the rise; however, maternal high-fructose intake may have adverse effects on offspring. We previously demonstrated that excessive fructose intake by rat dams altered steroidogenic gene transcription in the hippocampus of offspring. Herein, we examined how maternal high-fructose intake influences the regulation of adrenal glucocorticoid levels in offspring. Rat dams received 20% fructose solution during gestation and lactation. After weaning, the offspring were provided normal water. Maternal high-fructose intake did not alter mRNA expression levels of adrenal corticosterone-synthesizing and corticosterone-inactivating proteins or the circulating adrenocorticotropic hormone levels of offspring at postnatal day (PD) 21; however, it increased circulating corticosterone levels and decreased mRNA and protein levels of adrenal 5α-reductase type 1 and 11ß-hydroxysteroid dehydrogenase type 2 in offspring at PD160. Furthermore, maternal high-fructose intake enhanced DNA methylation of the adrenal 5α-reductase 1 promoter region in PD160 offspring. Thus, maternal high-fructose intake was found to affect adrenal steroid hormone clearance in adult offspring - at least in part - through epigenetic mechanisms.
Assuntos
Glândulas Suprarrenais/metabolismo , Corticosterona/metabolismo , Frutose/efeitos adversos , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/genética , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Glândulas Suprarrenais/efeitos dos fármacos , Hormônio Adrenocorticotrópico/metabolismo , Fatores Etários , Animais , Proteínas de Transporte/metabolismo , Metilação de DNA , Epigênese Genética , Feminino , Frutose/administração & dosagem , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos Sprague-Dawley , Receptores de GABA-A/metabolismo , DesmameRESUMO
AIMS: Recent increases in fructose consumption have raised concerns regarding the potential adverse intergenerational effects, as maternal fructose intake may induce physiological dysfunction in offspring. However, no reports are available regarding the effect of excess maternal fructose on reproductive tissues such as the ovary. Notably, the maternal intrauterine environment has been demonstrated to affect ovarian development in the subsequent generation. Given the fructose is transferred to the fetus, excess fructose consumption may affect offspring ovarian development. As ovarian development and its function is maintained by 17ß-estradiol, we therefore investigated whether excess maternal fructose intake influences offspring ovarian estradiol synthesis. Rats received a 20% fructose solution during gestation and lactation. After weaning, offspring ovaries were isolated. KEY FINDINGS: Offspring from fructose-fed dams showed reduced StAR and P450(17α) mRNA levels, along with decreased protein expression levels. Conversely, attenuated P450arom protein level was found in the absence of mRNA expression alteration. Consistent with these phenomena, decreased circulating levels of estradiol were observed. Furthermore, estrogen receptor α (ERα) protein levels were also down-regulated. In accordance, the mRNA for progesterone receptor, a transcriptional target of ERα, was decreased. These results suggest that maternal fructose might alter ovarian physiology in the subsequent generation.
