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

Overview

Journal Nutrients

Date 2020 Oct 10

PMID 33036430

Citations 2

Authors

Gizela A Pereira

Frhancielly S Sodre

Gilson M Murata

Andressa G Amaral

Tanyara B Payolla

Carolina V Campos

Fabio T Sato

Gabriel F Anhe

Silvana Bordin

Affiliations

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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.

Citing Articles

Low Birth Weight Intensifies Changes in Markers of Hepatocarcinogenesis Induced by Fructose Consumption in Rats.

Almeida L, Jordao Teixeira C, Campos C, Casaloti L, Sodre F, Capetini V Metabolites. 2022; 12(10).

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Tako E Nutrients. 2020; 12(11).

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References

Trinder P . Determination of blood glucose using an oxidase-peroxidase system with a non-carcinogenic chromogen. J Clin Pathol. 1969; 22(2):158-61. PMC: 474026. DOI: 10.1136/jcp.22.2.158. View

Romero-Calvo I, Ocon B, Martinez-Moya P, Suarez M, Zarzuelo A, Martinez-Augustin O . Reversible Ponceau staining as a loading control alternative to actin in Western blots. Anal Biochem. 2010; 401(2):318-20. DOI: 10.1016/j.ab.2010.02.036. View

Haidari M, Leung N, Mahbub F, Uffelman K, Kohen-Avramoglu R, Lewis G . Fasting and postprandial overproduction of intestinally derived lipoproteins in an animal model of insulin resistance. Evidence that chronic fructose feeding in the hamster is accompanied by enhanced intestinal de novo lipogenesis and.... J Biol Chem. 2002; 277(35):31646-55. DOI: 10.1074/jbc.M200544200. View

Chan S, Sun R, Zeng X, Choong Z, Wang H, Watt M . Activation of PPARα ameliorates hepatic insulin resistance and steatosis in high fructose-fed mice despite increased endoplasmic reticulum stress. Diabetes. 2013; 62(6):2095-105. PMC: 3661626. DOI: 10.2337/db12-1397. View

Iizuka K . The Role of Carbohydrate Response Element Binding Protein in Intestinal and Hepatic Fructose Metabolism. Nutrients. 2017; 9(2). PMC: 5331612. DOI: 10.3390/nu9020181. View

Douard V, Ferraris R . Regulation of the fructose transporter GLUT5 in health and disease. Am J Physiol Endocrinol Metab. 2008; 295(2):E227-37. PMC: 2652499. DOI: 10.1152/ajpendo.90245.2008. View

Kim M, Krawczyk S, Doridot L, Fowler A, Wang J, Trauger S . ChREBP regulates fructose-induced glucose production independently of insulin signaling. J Clin Invest. 2016; 126(11):4372-4386. PMC: 5096918. DOI: 10.1172/JCI81993. View

Zammit V, Newsholme E . The maximum activities of hexokinase, phosphorylase, phosphofructokinase, glycerol phosphate dehydrogenases, lactate dehydrogenase, octopine dehydrogenase, phosphoenolpyruvate carboxykinase, nucleoside diphosphatekinase, glutamate-oxaloacetate.... Biochem J. 1976; 160(3):447-62. PMC: 1164260. DOI: 10.1042/bj1600447. View

Payolla T, Teixeira C, Sato F, Murata G, Zonta G, Sodre F . In Utero Dexamethasone Exposure Exacerbates Hepatic Steatosis in Rats That Consume Fructose During Adulthood. Nutrients. 2019; 11(9). PMC: 6770256. DOI: 10.3390/nu11092114. View

10.

Uchida H, Nakajima Y, Ohtake K, Ito J, Morita M, Kamimura A . Protective effects of oral glutathione on fasting-induced intestinal atrophy through oxidative stress. World J Gastroenterol. 2017; 23(36):6650-6664. PMC: 5643286. DOI: 10.3748/wjg.v23.i36.6650. View

11.

Jang C, Hui S, Lu W, Cowan A, Morscher R, Lee G . The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids. Cell Metab. 2018; 27(2):351-361.e3. PMC: 6032988. DOI: 10.1016/j.cmet.2017.12.016. View

12.

Theytaz F, De Giorgi S, Hodson L, Stefanoni N, Rey V, Schneiter P . Metabolic fate of fructose ingested with and without glucose in a mixed meal. Nutrients. 2014; 6(7):2632-49. PMC: 4113761. DOI: 10.3390/nu6072632. View

13.

Oron-Herman M, Kamari Y, Grossman E, Yeger G, Peleg E, Shabtay Z . Metabolic syndrome: comparison of the two commonly used animal models. Am J Hypertens. 2008; 21(9):1018-22. DOI: 10.1038/ajh.2008.218. View

14.

Penhoat A, Fayard L, Stefanutti A, Mithieux G, Rajas F . Intestinal gluconeogenesis is crucial to maintain a physiological fasting glycemia in the absence of hepatic glucose production in mice. Metabolism. 2013; 63(1):104-11. DOI: 10.1016/j.metabol.2013.09.005. View

15.

Mithieux G, Bady I, Gautier A, Croset M, Rajas F, Zitoun C . Induction of control genes in intestinal gluconeogenesis is sequential during fasting and maximal in diabetes. Am J Physiol Endocrinol Metab. 2003; 286(3):E370-5. DOI: 10.1152/ajpendo.00299.2003. View

16.

Santos-Silva J, da Silva P, de Souza D, Jordao Teixeira C, Bordin S, Anhe G . In utero exposure to dexamethasone programs the development of the pancreatic β- and α-cells during early postnatal life. Life Sci. 2020; 255:117810. DOI: 10.1016/j.lfs.2020.117810. View

17.

Nyirenda M, Welberg L, Seckl J . Programming hyperglycaemia in the rat through prenatal exposure to glucocorticoids-fetal effect or maternal influence?. J Endocrinol. 2001; 170(3):653-60. DOI: 10.1677/joe.0.1700653. View

18.

Drozdowski L, Iordache C, Clandinin M, Wild G, Todd Z, Thomson A . A combination of dexamethasone and glucagon-like peptide-2 increase intestinal morphology and glucose uptake in suckling rats. J Pediatr Gastroenterol Nutr. 2005; 42(1):32-9. DOI: 10.1097/01.mpg.0000187246.60560.16. View

19.

Opie L, Newsholme E . The activities of fructose 1,6-diphosphatase, phosphofructokinase and phosphoenolpyruvate carboxykinase in white muscle and red muscle. Biochem J. 1967; 103(2):391-9. PMC: 1270420. DOI: 10.1042/bj1030391. View

20.

Chen Y, Hu Y, Yang Q, Son J, Liu X, de Avila J . Excessive Glucocorticoids During Pregnancy Impair Fetal Brown Fat Development and Predispose Offspring to Metabolic Dysfunctions. Diabetes. 2020; 69(8):1662-1674. PMC: 7372078. DOI: 10.2337/db20-0009. View