Influence of Maternal Hypercholesterolemia and Phytosterol Intervention During Gestation and Lactation on Dyslipidemia and Hepatic Lipid Metabolism in Offspring of Syrian Golden Hamsters

Overview

Journal Mol Nutr Food Res

Specialty Nutritional Sciences

Date 2016 May 24

PMID 27213832

Citations 9

Authors

Jie Liu

Aadil Iqbal

Amy Raslawsky

Richard W Browne

Mulchand S Patel

Todd C Rideout

Affiliations

Soon will be listed here.

Abstract

Scope: Although there is a normal physiological rise in maternal lipids during pregnancy, excessive maternal hyperlipidemia during pregnancy increases cardiovascular disease risk for both the mother and offspring. There are limited safe lipid-lowering treatment options for use during pregnancy, therefore, we evaluated the influence of maternal phytosterol (PS) supplementation on lipid and lipoprotein metabolism in mothers and progeny.

Methods And Results: Female Syrian golden hamsters were randomly assigned to three diets throughout prepregnancy, gestation, and lactation (n = 6/group): (i) Chow (Chow), (ii) chow with 0.5% cholesterol (CH), and (iii) chow with 0.5% CH and 2% PS (CH/PS). Compared with newly weaned pups from Chow dams, pups from dams fed the CH-enriched diet demonstrated increases (p < 0.05) in total-C, LDL-C, HDL-C, and total LDL and VLDL particle number. Pups from CH-fed mothers also exhibited higher hepatic CH concentration and differential mRNA expression pattern of CH regulatory genes. Pups from PS-supplemented dams demonstrated reductions (p < 0.05) in serum total-C, non-HDL-C, and LDL-C but also increased triglycerides compared with pups from CH-fed dams. Maternal PS supplementation reduced (p < 0.05) hepatic CH and increased the abundance of HMG-CoAr and LDLr protein in newly weaned pups compared with the CH group.

Conclusion: Results suggest that maternal PS supplementation is largely effective in normalizing CH in pups born to mothers with hypercholesterolemia, however, the cause and long-term influence of increased triglyceride is not known.

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References

Whittaker M, Frankos V, Wolterbeek A, Waalkens-Berendsen D . Two-generation reproductive toxicity study of plant stanol esters in rats. Regul Toxicol Pharmacol. 1999; 29(2 Pt 1):196-204. DOI: 10.1006/rtph.1999.1288. View

Rideout T, Ramprasath V, Griffin J, Browne R, Harding S, Jones P . Phytosterols protect against diet-induced hypertriglyceridemia in Syrian golden hamsters. Lipids Health Dis. 2014; 13:5. PMC: 3896966. DOI: 10.1186/1476-511X-13-5. View

Baardman M, Kerstjens-Frederikse W, Berger R, Bakker M, Hofstra R, Plosch T . The role of maternal-fetal cholesterol transport in early fetal life: current insights. Biol Reprod. 2012; 88(1):24. DOI: 10.1095/biolreprod.112.102442. View

Rideout T, Harding S, Mackay D, AbuMweis S, Jones P . High basal fractional cholesterol synthesis is associated with nonresponse of plasma LDL cholesterol to plant sterol therapy. Am J Clin Nutr. 2010; 92(1):41-6. DOI: 10.3945/ajcn.2009.29073. View

Jeyarajah E, Cromwell W, Otvos J . Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy. Clin Lab Med. 2006; 26(4):847-70. DOI: 10.1016/j.cll.2006.07.006. View

Laitinen K, Isolauri E, Kaipiainen L, Gylling H, Miettinen T . Plant stanol ester spreads as components of a balanced diet for pregnant and breast-feeding women: evaluation of clinical safety. Br J Nutr. 2008; 101(12):1797-804. DOI: 10.1017/S0007114508133608. View

Harding S, Rideout T, Jones P . Hepatic nuclear sterol regulatory binding element protein 2 abundance is decreased and that of ABCG5 increased in male hamsters fed plant sterols. J Nutr. 2010; 140(7):1249-54. DOI: 10.3945/jn.109.120311. View

Ryokkynen A, Kayhko U, Mustonen A, Kukkonen J, Nieminen P . Multigenerational exposure to phytosterols in the mouse. Reprod Toxicol. 2005; 19(4):535-40. DOI: 10.1016/j.reprotox.2004.09.003. View

Marseille-Tremblay C, Gravel A, Lafond J, Mounier C . Effect of an enriched cholesterol diet during gestation on fatty acid synthase, HMG-CoA reductase and SREBP-1/2 expressions in rabbits. Life Sci. 2007; 81(9):772-8. DOI: 10.1016/j.lfs.2007.07.016. View

10.

Montoudis A, Simoneau L, Brissette L, Forest J, Savard R, Lafond J . Impact of a cholesterol enriched diet on maternal and fetal plasma lipids and fetal deposition in pregnant rabbits. Life Sci. 1999; 64(26):2439-50. DOI: 10.1016/s0024-3205(99)00201-5. View

11.

Napoli C, DArmiento F, Mancini F, Postiglione A, Witztum J, Palumbo G . Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest. 1998; 100(11):2680-90. PMC: 508471. DOI: 10.1172/JCI119813. View

12.

Waalkens-Berendsen D, Wolterbeek A, Wijnands M, Richold M, Hepburn P . Safety evaluation of phytosterol esters. Part 3. Two-generation reproduction study in rats with phytosterol esters--a novel functional food. Food Chem Toxicol. 1999; 37(7):683-96. DOI: 10.1016/s0278-6915(99)00056-3. View

13.

Eapen D, Valiani K, Reddy S, Sperling L . Management of familial hypercholesterolemia during pregnancy: case series and discussion. J Clin Lipidol. 2012; 6(1):88-91. DOI: 10.1016/j.jacl.2011.08.005. View

14.

Rideout T, Yuan Z, Bakovic M, Liu Q, Li R, Mine Y . Guar gum consumption increases hepatic nuclear SREBP2 and LDL receptor expression in pigs fed an atherogenic diet. J Nutr. 2007; 137(3):568-72. DOI: 10.1093/jn/137.3.568. View

15.

MacPherson R, Castelli L, Miotto P, Frendo-Cumbo S, Milburn A, Roy B . A maternal high fat diet has long-lasting effects on skeletal muscle lipid and PLIN protein content in rat offspring at young adulthood. Lipids. 2015; 50(2):205-17. DOI: 10.1007/s11745-014-3985-5. View

16.

Haggarty P . Placental regulation of fatty acid delivery and its effect on fetal growth--a review. Placenta. 2002; 23 Suppl A:S28-38. DOI: 10.1053/plac.2002.0791. View

17.

Porkka K, Viikari J, Taimela S, Dahl M, Akerblom H . Tracking and predictiveness of serum lipid and lipoprotein measurements in childhood: a 12-year follow-up. The Cardiovascular Risk in Young Finns study. Am J Epidemiol. 1994; 140(12):1096-110. DOI: 10.1093/oxfordjournals.aje.a117210. View

18.

Rideout T, Harding S, Jones P . Consumption of plant sterols reduces plasma and hepatic triglycerides and modulates the expression of lipid regulatory genes and de novo lipogenesis in C57BL/6J mice. Mol Nutr Food Res. 2010; 54 Suppl 1:S7-13. DOI: 10.1002/mnfr.201000027. View

19.

Agnish N, Keller K . The rationale for culling of rodent litters. Fundam Appl Toxicol. 1997; 38(1):2-6. DOI: 10.1006/faat.1997.2318. View

20.

Goharkhay N, Tamayo E, Yin H, Hankins G, Saade G, Longo M . Maternal hypercholesterolemia leads to activation of endogenous cholesterol synthesis in the offspring. Am J Obstet Gynecol. 2008; 199(3):273.e1-6. PMC: 2574210. DOI: 10.1016/j.ajog.2008.06.064. View