Early life exposure to certain environmental stimuli is related to the development of alternative phenotypes in mammals. A number of these phenotypes are related to an increased risk of disease later in life, creating a massive healthcare burden. With recent focus on the determination of underlying causes of common metabolic disorders, parental nutrition is of great interest, mainly due to a global shift towards a Western-type diet. Recent studies focusing on the increase of food or macronutrient intake don't always consider the source of these nutrients as an important factor. In our study, we concentrate on the effects of high-sucrose diet, which provides carbohydrates in form of sucrose as opposed to starch in standard diet, fed in pregnancy and lactation in two subsequent generations of spontaneously hypertensive rats (SHR) and congenic SHR-Zbtb16 rats. Maternal sucrose intake increased fasting glycaemia in SHR female offspring in adulthood and increased their chow consumption in gravidity. High-sucrose diet fed to the maternal grandmother increased brown fat weight and HDL cholesterol levels in adult male offspring of both strains, i.e., the grandsons. Fasting glycaemia was however decreased only in SHR offspring. In conclusion, we show the second-generation effects of maternal exposition to a high-sucrose diet, some modulated to a certain extent by variation in the Zbtb16 gene.

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University and the General University Hospital 128 00 Prague Czech Republic

Zobrazit více v PubMed

Bloomfield F.H., Harding J.E. Experimental aspects of nutrition and fetal growth. Fetal Matern. Med. Rev. 1998;10:91–107. doi: 10.1017/S0965539597000235. DOI

Singal R., Ginder G.D. DNA methylation. Blood. 1999;93:4059–4070. doi: 10.1182/blood.V93.12.4059. PubMed DOI

Delage B., Dashwood R.H. Dietary manipulation of histone structure and function. Annu. Rev. Nutr. 2008;28:347–366. doi: 10.1146/annurev.nutr.28.061807.155354. PubMed DOI PMC

Fernandez-Twinn D.S., Hjort L., Novakovic B., Ozanne S.E., Saffery R. Intrauterine programming of obesity and type 2 diabetes. Diabetologia. 2019;62:1789–1801. doi: 10.1007/s00125-019-4951-9. PubMed DOI PMC

Waterland R.A., Jirtle R.L. Transposable elements: Targets for early nutritional effects on epigenetic gene regulation. Mol. Cell Biol. 2003;23:5293–5300. doi: 10.1128/MCB.23.15.5293-5300.2003. PubMed DOI PMC

Skinner M.K. Role of epigenetics in developmental biology and transgenerational inheritance. Birth Defects Res. C Embryo Today. 2011;93:51–55. doi: 10.1002/bdrc.20199. PubMed DOI PMC

Skinner M.K. Environmental epigenetic transgenerational inheritance and somatic epigenetic mitotic stability. Epigenetics. 2011;6:838–842. PubMed PMC

Skolnikova E., Sedova L., Krenova D., Kren V., Seda O. Mutation in Zbtb16 gene plays a role in lipid profiles of pregnant rats and their offspring after high-Sucrose diet feeding. Atherosclerosis. 2017;263:E36–E37. doi: 10.1016/j.atherosclerosis.2017.06.136. DOI

Warrington N.M., Beaumont R.N., Horikoshi M., Day F.R., Helgeland Ø., Laurin C., Bacelis J., Peng S., Hao K., Feenstra B., et al. Maternal and fetal genetic effects on birth weight and their relevance to cardio-Metabolic risk factors. Nat. Genet. 2019;51:804–814. doi: 10.1038/s41588-019-0403-1. PubMed DOI PMC

Heard E., Martienssen R.A. Transgenerational epigenetic inheritance: Myths and mechanisms. Cell. 2014;2014 157:95–109. doi: 10.1016/j.cell.2014.02.045. PubMed DOI PMC

Skinner M.K. What is an epigenetic transgenerational phenotype? F3 or F2. Reprod. Toxicol. 2008;25:2–6. doi: 10.1016/j.reprotox.2007.09.001. PubMed DOI PMC

Jou M.Y., Lönnerdal B., Philipps A.F. Maternal zinc restriction affects postnatal growth and glucose homeostasis in rat offspring differently depending upon adequacy of their nutrient intake. Pediatr. Res. 2012;71:228e34. doi: 10.1038/pr.2011.44. PubMed DOI

Muthayya S., Kurpad A.V., Duggan C.P., Bosch R.J., Dwarkanath P., Mhaskar A., Mhaskar R., Thomas A., Vaz M., Bhat S., et al. Low maternal vitamin B12 status is associated with intrauterine growth retardation in urban South Indians. Eur. J. Clin. Nutr. 2006;60:791–801. doi: 10.1038/sj.ejcn.1602383. PubMed DOI

Yajnik C.S., Deshpande S.S., Jackson A.A., Refsum H., Rao S., Fisher D.J., Bhat D.S., Naik S.S., Coyaji K.J., Joglekar C.V., et al. Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: The Pune Maternal Nutrition Study. Diabetologia. 2008;51:29–38. doi: 10.1007/s00125-007-0793-y. PubMed DOI PMC

Ainge H., Thompson C., Ozanne S.E., Rooney K.B. A systematic review on animal models of maternal high fat feeding and offspring glycaemic control. Int. J. Obes. 2011;35:325–335. doi: 10.1038/ijo.2010.149. PubMed DOI

Bocarsly M.E., Barson J.R., Hauca J.M., Hoebel B.G., Leibowitz S.F., Avena N.M. Effects of perinatal exposure to palatable diets on body weight and sensitivity to drugs of abuse in rats. Physiol. Behav. 2012;107:568–575. doi: 10.1016/j.physbeh.2012.04.024. PubMed DOI PMC

Ng S.F., Lin R.C., Laybutt D.R., Barres R., Owens J.A., Morris M.J. Chronic high-Fat diet in fathers programs beta-Cell dysfunction in female rat offspring. Nature. 2010;467:963–966. doi: 10.1038/nature09491. PubMed DOI

Šeda O., Šedová L., Včelák J., Vaňková M., Liška F., Bendlová B. ZBTB16 and metabolic syndrome: A network perspective. Physiol. Res. 2017;66:S357–S365. doi: 10.33549/physiolres.933730. PubMed DOI

Chen S., Qian J., Shi X., Gao T., Liang T., Liu C. Control of hepatic gluconeogenesis by the promyelocytic leukemia zinc finger protein. Mol. Endocrinol. 2014;28:1987–1998. doi: 10.1210/me.2014-1164. PubMed DOI PMC

Liška F., Landa V., Zídek V., Mlejnek P., Šilhavý J., Šimáková M., Strnad H., Trnovská J., Škop V., Kazdová L. Downregulation of Plzf gene ameliorates metabolic and cardiac traits in the spontaneously hypertensive rat. Hypertension. 2017;69:1084–1091. doi: 10.1161/HYPERTENSIONAHA.116.08798. PubMed DOI

Aitman T.J., Gotoda T., Evans A.L., Imrie H., Heath K.E., Trembling P.M., Truman H., Wallace C.A., Rahman A., Doré C., et al. Quantitative trait loci for cellular defects in glucose and fatty acid metabolism in hypertensive rats. Nat. Genet. 1997;16:197–201. doi: 10.1038/ng0697-197. PubMed DOI

Pravenec M., Křen V., Landa V., Mlejnek P., Musilová A., Šilhavý J., Šimáková M., Zídek V. Recent progress in the genetics of spontaneously hypertensive rats. Physiol. Res. 2014;63:S1–S8. PubMed

Sedova L., Kazdova L., Seda O., Krenova D., Kren V. Rat inbred PD/Cub strain as a model of dyslipidemia and insulin resistance. Folia Biol. (Praha) 2000;46:99–106. PubMed

Seda O., Liska F., Sedova L., Kazdova L., Krenova D., Kren V. A 14-Gene region of rat chromosome 8 in SHR-Derived polydactylous congenic substrain affects muscle-Specific insulin resistance, dyslipidaemia and visceral adiposity. Folia Biol.-Prague. 2005;51:53–61. PubMed

Krupková M., Liška F., Kazdová L., Šedová L., Kábelová A., Křenová D., Křen V., Šeda O. Single-Gene Congenic Strain Reveals the Effect of Zbtb16 on Dexamethasone-Induced Insulin Resistance. Front. Endocrinol. (Lausanne) 2018;9:185. doi: 10.3389/fendo.2018.00185. PubMed DOI PMC

Usui S., Hara Y., Hosaki S., Okazaki M. A new on-Line dual enzymatic method for simultaneous quantification of cholesterol and triglycerides in lipoproteins by HPLC. J. Lipid Res. 2002;43:805–814. PubMed

Heikkinen S., Argmann C.A., Champy M.F., Auwerx J. Evaluation of glucose homeostasis. Curr. Protoc. Mol. Biol. 2007 doi: 10.1002/0471142727.mb29b03s77. PubMed DOI

Gluckman P.D., Hanson M.A. Developmental origins of disease paradigm: A mechanistic and evolutionary perspective. Pediatr. Res. 2004;56:311–317. doi: 10.1203/01.PDR.0000135998.08025.FB. PubMed DOI

Kisioglu B., Nergiz-Unal R. Potential effect of maternal dietary sucrose or fructose syrup on CD36, leptin, and ghrelin-Mediated fetal programming of obesity. Nutr. Neurosci. 2018 doi: 10.1080/1028415X.2018.1491151. PubMed DOI

Lowette K., Roosen L., Tack J., Vanden Berghe P. Effects of high-fructose diets on central appetite signaling and cognitive function. Front. Nutr. 2015;2:5. doi: 10.3389/fnut.2015.00005. PubMed DOI PMC

Tschritter O., Fritsche A., Shirkavand F., Machicao F., Häring H., Stumvoll M. Assessing the shape of the glucose curve during an oral glucose tolerance test. Diabetes Care. 2003;26:1026–1033. doi: 10.2337/diacare.26.4.1026. PubMed DOI

Gluckman P.D., Hanson M.A. The developmental origins of the metabolic syndrome. Trends Endocrinol. Metab. 2004;15:183–187. doi: 10.1016/j.tem.2004.03.002. PubMed DOI

Gluckman P.D., Hanson M.A., Spencer H.G. Predictive adaptive responses and human evolution. Trends Ecol. Evol. 2005;20:527–533. doi: 10.1016/j.tree.2005.08.001. PubMed DOI

Hopkins G.J., Barter P.J. Role of triglyceride-Rich lipoproteins and hepatic lipase in determining the particle size and composition of high density lipoproteins. J. Lipid Res. 1986;27:1265–1277. PubMed

Dumortier O., Roger E., Pisani D.F., Casamento V., Gautier N., Lebrun P., Johnston H., Lopez P., Amri E.Z., Jousse C. Age-dependent control of energy homeostasis by brown adipose tissue in progeny subjected to maternal diet-Induced fetal programming. Diabetes. 2017;66:627–639. doi: 10.2337/db16-0956. PubMed DOI

Chusyd D.E., Wang D., Huffman D.M., Nagy T.R. Relationships between rodent white adipose fat pads and human white adipose fat depots. Front. Nutr. 2016;3:10. doi: 10.3389/fnut.2016.00010. PubMed DOI PMC

Liska F., Snajdr P., Sedova L., Seda O., Chylikova B., Slamova P., Krejci E., Sedmera D., Grim M., Krenova D., et al. Deletion of a conserved noncoding sequence in Plzf intron leads to Plzf down-Regulation in limb bud and polydactyly in the rat. Dev. Dyn. 2009;238:673–684. doi: 10.1002/dvdy.21859. PubMed DOI

Sedova L., Seda O., Kazdová L., Chylíková B., Hamet P., Tremblay J., Kren V., Krenová D. Sucrose feeding during pregnancy and lactation elicits distinct metabolic response in offspring of an inbred genetic model of metabolic syndrome. Am. J. Physiol. Endocrinol. Metab. 2017;292:E1318–E1324. doi: 10.1152/ajpendo.00526.2006. PubMed DOI

Parental overnutrition by carbohydrates in developmental origins of metabolic syndrome

Maternal High-Sucrose Diet Affects Phenotype Outcome in Adult Male Offspring: Role of Zbtb16