Dataset Information

Fructose Consumption by Adult Rats Exposed to Dexamethasone In Utero Changes the Phenotype of Intestinal Epithelial Cells and Exacerbates Intestinal Gluconeogenesis.

ABSTRACT: Fructose consumption by rodents modulates both hepatic and intestinal lipid metabolism and gluconeogenesis. We have previously demonstrated that in utero exposure to dexamethasone (DEX) interacts with fructose consumption during adult life to exacerbate hepatic steatosis in rats. The aim of this study was to clarify if adult rats born to DEX-treated mothers would display differences in intestinal gluconeogenesis after excessive fructose intake. To address this issue, female Wistar rats were treated with DEX during pregnancy and control (CTL) mothers were kept untreated. Adult offspring born to CTL and DEX-treated mothers were assigned to receive either tap water (Control-Standard Chow (CTL-SC) and Dexamethasone-Standard Chow (DEX-SC)) or 10% fructose in the drinking water (CTL-fructose and DEX-fructose). Fructose consumption lasted for 80 days. All rats were subjected to a 40 h fasting before sample collection. We found that DEX-fructose rats have increased glucose and reduced lactate in the portal blood. Jejunum samples of DEX-fructose rats have enhanced phosphoenolpyruvate carboxykinase (PEPCK) expression and activity, higher facilitated glucose transporter member 2 (GLUT2) and facilitated glucose transporter member 5 (GLUT5) content, and increased villous height, crypt depth, and proliferating cell nuclear antigen (PCNA) staining. The current data reveal that rats born to DEX-treated mothers that consume fructose during adult life have increased intestinal gluconeogenesis while recapitulating metabolic and morphological features of the neonatal jejunum phenotype.

SUBMITTER: Pereira GA

PROVIDER: S-EPMC7600908 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fructose Consumption by Adult Rats Exposed to Dexamethasone In Utero Changes the Phenotype of Intestinal Epithelial Cells and Exacerbates Intestinal Gluconeogenesis.

Pereira Gizela A GA Sodré Frhancielly S FS Murata Gilson M GM Amaral Andressa G AG Payolla Tanyara B TB Campos Carolina V CV Sato Fabio T FT Anhê Gabriel F GF Bordin Silvana S

Nutrients 20201007 10

Fructose consumption by rodents modulates both hepatic and intestinal lipid metabolism and gluconeogenesis. We have previously demonstrated that in utero exposure to dexamethasone (DEX) interacts with fructose consumption during adult life to exacerbate hepatic steatosis in rats. The aim of this study was to clarify if adult rats born to DEX-treated mothers would display differences in intestinal gluconeogenesis after excessive fructose intake. To address this issue, female Wistar rats were trea ...[more]

PMID: 33036430

Similar Datasets

Project description:OBJECTIVE:Fructose is commonplace in Western diets and is consumed primarily through added sugars as sucrose or high fructose corn syrup. High consumption of fructose has been linked to the development of metabolic disorders, such as cardiovascular diseases. The majority of the harmful effects of fructose can be traced to its uncontrolled and rapid metabolism, primarily within the liver. It has been speculated that the formulation of fructose-containing sweeteners can have varying impacts on its adverse effects. Unfortunately, there is limited data supporting this hypothesis. The objective of this study was to examine the impact of different fructose-containing sweeteners on the intestinal, hepatic, and oral bioavailability of fructose. METHODS:Portal and femoral vein catheters were surgically implanted in male Wistar rats. Animals were gavaged with a 1 g/kg carbohydrate solution consisting of fructose, 45% glucose/55% fructose, sucrose, glucose, or water. Blood samples were then collected from the portal and systemic circulation. Fructose levels were measured and pharmacokinetic parameters were calculated. RESULTS:Compared to animals that were gavaged with 45% glucose/55% fructose or sucrose, fructose-gavaged animals had a 40% greater fructose area under the curve and a 15% greater change in maximum fructose concentration in the portal circulation. In the systemic circulation of fructose-gavaged animals, the fructose area under the curve was 17% and 24% higher and the change in the maximum fructose concentration was 15% and 30% higher than the animals that received 45% glucose/55% fructose or sucrose, respectively. After the oral administration of fructose, 45% glucose/55% fructose, and sucrose, the bioavailability of fructose was as follows: intestinal availability was 0.62, 0.53 and 0.57; hepatic availability was 0.33, 0.45 and 0.45; and oral bioavailability was 0.19, 0.23 and 0.24, respectively. CONCLUSIONS:Our studies show that the co-ingestion of glucose did not enhance fructose absorption, rather, it decreased fructose metabolism in the liver. The intestinal, hepatic, and oral bioavailability of fructose was similar between 45% glucose/55% fructose and sucrose.

Project description:BackgroundAlcohol exposure in utero increases susceptibility to carcinogen-induced mammary tumorigenesis in adult offspring and causes tumors with a more malignant phenotype. This study was conducted to identify changes early in tumor development that might lead to this outcome.MethodsPregnant Sprague-Dawley rats were fed a liquid diet containing 6.7% ethanol (alcohol), an isocaloric liquid diet without alcohol (pair-fed), or rat chow ad libitum (ad lib) from gestation day 7 until parturition. At birth, female progeny were cross-fostered to control dams. Pups were weaned at postnatal day (PND) 21 and fed rat chow ad libitum for the remainder of the experiment. Female offspring were administered N-nitroso-N-methylurea (NMU; 50 mg/kg body weight) on PND 50. Mammary glands were palpated weekly, and offspring were euthanized at 16 weeks post-NMU injection.ResultsAt 16 weeks post-NMU, tumor multiplicity was greater in alcohol-exposed offspring compared with control groups. Estrogen receptor-α (ER) mRNA expression was decreased in tumors from alcohol-exposed offspring, and these animals developed more ER-negative tumors relative to the pair-fed group. Alcohol-exposed offspring also tended to develop more progesterone receptor (PR)-positive tumors. All tumors were HER2-negative. PR positivity was associated with higher Ki67 expression, suggesting that PR-positive tumors were more proliferative. Tumors from alcohol-exposed animals exhibited increased mRNA expression of the insulin-like growth factor (IGF) family members IGF-II and IGFBP-5. IGF-II and DNA methyltransferase mRNA tended to be greater in the normal contralateral mammary glands of these animals.ConclusionsThese data indicate that alcohol exposure in utero may shift NMU-induced tumor development toward a more aggressive phenotype and that alterations in IGF-II expression may contribute to these changes. Additional studies should be aimed at epigenetic mechanisms that underlie IGF-II expression to further delineate how this gene is altered in mammary glands of adults exposed to alcohol in utero.

Project description:Although both alcohol and fructose are particularly steatogenic, their long-term effect in the development of a metabolic syndrome has not been studied in vivo. Consumption of fructose generally leads to obesity, whereas ethanol can induce liver damage in the absence of overweight. Here, Sprague-Dawley rats were fed ad libitum for 28 days on five diets: chow (control), liquid Lieber-DeCarli (LDC) diet, LDC +30%J of ethanol (L-Et) or fructose (L-Fr), and LDC combined with 30%J ethanol and 30%J fructose (L-EF). Body weight (BW) and liver weight (LW) were measured. Blood and liver samples were harvested and subjected to biochemical tests, histopathological examinations, and RT-PCR. Alcohol-containing diets substantially reduced the food intake and BW (?3rd week), whereas fructose-fed animals had higher LW than controls (P<0.05). Additionally, leukocytes, plasma AST and leptin levels were the highest in the fructose-administered rats. Compared to the chow and LDC diets, the L-EF diet significantly elevated blood glucose, insulin, and total-cholesterol levels (also vs. the L-Et group). The albumin and Quick-test levels were the lowest, whereas ALT activity was the highest in the L-EF group. Moreover, the L-EF diet aggravated plasma triglyceride and reduced HDL-cholesterol levels more than 2.7-fold compared to the sum of the effects of the L-Et and L-Fr diets. The decreased hepatic insulin clearance in the L-EF group vs. control and LDC groups was reflected by a significantly decreased C-peptide:insulin ratio. All diets except the control caused hepatosteatosis, as evidenced by Nile red and H&E staining. Hepatic transcription of insulin receptor substrate-1/2 was mainly suppressed by the L-Fr and L-EF diets. The L-EF diet did not enhance the mitochondrial ?-oxidation of fatty acids (Cpt1? and Ppar-? expressions) compared to the L-Et or L-Fr diet. Together, our data provide evidence for the coaction of ethanol and fructose with a high-fat-diet on dyslipidemia and insulin resistance-accompanied liver damage.

Dataset Information

Fructose Consumption by Adult Rats Exposed to Dexamethasone In Utero Changes the Phenotype of Intestinal Epithelial Cells and Exacerbates Intestinal Gluconeogenesis.

Publications

Fructose Consumption by Adult Rats Exposed to Dexamethasone In Utero Changes the Phenotype of Intestinal Epithelial Cells and Exacerbates Intestinal Gluconeogenesis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets