Maternal Quercetin Administration During Gestation and Lactation Decrease Endoplasmic Reticulum Stress and Related Inflammation in the Adult Offspring of Obese Female Rats

Overview

Journal Eur J Nutr

Specialty Nutritional Sciences

Date 2014 Feb 27

PMID 24570028

Citations 25

Authors

Zhenghao Wu

Jiaxi Zhao

Hao Xu

Ying Lyv

Xin Feng

Yuehui Fang

Yajun Xu

Affiliations

Soon will be listed here.

Abstract

Purpose: Maternal obesity is a risk factor for metabolic diseases in offspring. The aim of this study was to investigate whether quercetin administration during gestation and lactation could have any protective effect against the impact of maternal obesity on increased sensitivity to obesity and metabolic disorders in offspring.

Methods: Female Sprague-Dawley rats were fed a high-fat diet to induce obesity. Obese dams were administered 0, 50, 100 or 200 mg/kg body weight (BW) quercetin intragastrically during gestation and lactation. Normal weight dams were used as controls. The F1 generation was fed with a standard diet after weaning, and blood glucose, lipids and inflammatory factors were assessed. Expression of biomarkers involved endoplasmic reticulum (ER) stress, and related inflammatory pathways in liver and adipose tissues were analyzed at postnatal day 100.

Results: Maternal obesity resulted in increased birth weight, postnatal BW gain, hyperglycemia, hyperlipemia, hyperinsulinemia, increased serum levels of inflammatory factors, and up-regulated biomarkers involved in ER stress and related inflammatory pathways in the offspring. Maternal quercetin intervention (QI) had significant ameliorating effects on maternal blood lipids, especially cholesterol, which resulted in improved glucose metabolism and insulin sensitivity and alleviated ER stress and related inflammation in the grown offspring of obese dams.

Conclusions: Maternal QI in obese dams during gestation and lactation reduced birth weight and postnatal BW gain in the offspring, and helped to improve insulin sensitivity and lipid metabolism of the mature offspring via reducing ER stress and related inflammation in the liver and adipose tissue.

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References

Egert S, Wolffram S, Bosy-Westphal A, Boesch-Saadatmandi C, Wagner A, Frank J . Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans. J Nutr. 2008; 138(9):1615-21. DOI: 10.1093/jn/138.9.1615. View

Poston L . Maternal obesity, gestational weight gain and diet as determinants of offspring long term health. Best Pract Res Clin Endocrinol Metab. 2012; 26(5):627-39. DOI: 10.1016/j.beem.2012.03.010. View

Boesch-Saadatmandi C, Loboda A, Wagner A, Stachurska A, Jozkowicz A, Dulak J . Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: role of miR-155. J Nutr Biochem. 2010; 22(3):293-9. DOI: 10.1016/j.jnutbio.2010.02.008. View

Seiva F, Chuffa L, Braga C, Amorim J, Fernandes A . Quercetin ameliorates glucose and lipid metabolism and improves antioxidant status in postnatally monosodium glutamate-induced metabolic alterations. Food Chem Toxicol. 2012; 50(10):3556-61. DOI: 10.1016/j.fct.2012.07.009. View

Tai M . A mathematical model for the determination of total area under glucose tolerance and other metabolic curves. Diabetes Care. 1994; 17(2):152-4. DOI: 10.2337/diacare.17.2.152. View

Katsuki A, Sumida Y, Murashima S, Murata K, Takarada Y, Ito K . Serum levels of tumor necrosis factor-alpha are increased in obese patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1998; 83(3):859-62. DOI: 10.1210/jcem.83.3.4618. View

Anhe G, Okamoto M, Kinote A, Sollon C, Lellis-Santos C, Anhe F . Quercetin decreases inflammatory response and increases insulin action in skeletal muscle of ob/ob mice and in L6 myotubes. Eur J Pharmacol. 2012; 689(1-3):285-93. DOI: 10.1016/j.ejphar.2012.06.007. View

Egert S, Rimbach G, Muller M . No evidence for a thermic effect of the dietary flavonol quercetin: a pilot study in healthy normal-weight women. Eur J Appl Physiol. 2010; 111(5):869-73. DOI: 10.1007/s00421-010-1674-5. View

Sullivan E, Smith M, Grove K . Perinatal exposure to high-fat diet programs energy balance, metabolism and behavior in adulthood. Neuroendocrinology. 2010; 93(1):1-8. PMC: 3700139. DOI: 10.1159/000322038. View

10.

Chen L, Egan L, Li Z, Greten F, Kagnoff M, Karin M . The two faces of IKK and NF-kappaB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion. Nat Med. 2003; 9(5):575-81. DOI: 10.1038/nm849. View

11.

Arkan M, Hevener A, Greten F, Maeda S, Li Z, Long J . IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med. 2005; 11(2):191-8. DOI: 10.1038/nm1185. View

12.

Kleemann R, Verschuren L, Morrison M, Zadelaar S, van Erk M, Wielinga P . Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Atherosclerosis. 2011; 218(1):44-52. DOI: 10.1016/j.atherosclerosis.2011.04.023. View

13.

Barker D, Gluckman P, Godfrey K, Harding J, Owens J, Robinson J . Fetal nutrition and cardiovascular disease in adult life. Lancet. 1993; 341(8850):938-41. DOI: 10.1016/0140-6736(93)91224-a. View

14.

Lee A . The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods. 2005; 35(4):373-81. DOI: 10.1016/j.ymeth.2004.10.010. View

15.

Panchal S, Poudyal H, Brown L . Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats. J Nutr. 2012; 142(6):1026-32. DOI: 10.3945/jn.111.157263. View

16.

Ozcan U, Cao Q, Yilmaz E, Lee A, Iwakoshi N, Ozdelen E . Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004; 306(5695):457-61. DOI: 10.1126/science.1103160. View

17.

Willhite C . Teratogenic potential of quercetin in the rat. Food Chem Toxicol. 1982; 20(1):75-9. DOI: 10.1016/s0278-6915(82)80012-4. View

18.

Barker D . Obesity and early life. Obes Rev. 2007; 8 Suppl 1:45-9. DOI: 10.1111/j.1467-789X.2007.00317.x. View

19.

Parikh N, Pencina M, Wang T, Lanier K, Fox C, DAgostino R . Increasing trends in incidence of overweight and obesity over 5 decades. Am J Med. 2007; 120(3):242-50. DOI: 10.1016/j.amjmed.2006.06.004. View

20.

Bayol S, Simbi B, Bertrand J, Stickland N . Offspring from mothers fed a 'junk food' diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females. J Physiol. 2008; 586(13):3219-30. PMC: 2538787. DOI: 10.1113/jphysiol.2008.153817. View