Hostname: page-component-cd9895bd7-gxg78 Total loading time: 0 Render date: 2024-12-22T09:03:28.516Z Has data issue: false hasContentIssue false
  • English
  • Français

The loss of ERE-dependent ERα signaling potentiates the effects of maternal high-fat diet on energy homeostasis in female offspring fed an obesogenic diet

Published online by Cambridge University Press:  23 September 2019

Troy A. Roepke Open the ORCID record for Troy A. Roepke [Opens in a new window] ,
Ali Yasrebi ,
Alejandra Villalobos ,
Elizabeth A. Krumm ,
Jennifer A. Yang  and
Kyle J. Mamounis
Troy A. Roepke*
Affiliation:
Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Graduate Program in Endocrinology and Animal Biosciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Nutritional Sciences Graduate Program, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA New Jersey Institute for Food, Nutrition, and Health, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
Ali Yasrebi
Affiliation:
Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Graduate Program in Endocrinology and Animal Biosciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
Alejandra Villalobos
Affiliation:
Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
Elizabeth A. Krumm
Affiliation:
Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Graduate Program in Endocrinology and Animal Biosciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
Jennifer A. Yang
Affiliation:
Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Graduate Program in Endocrinology and Animal Biosciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
Kyle J. Mamounis
Affiliation:
Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Nutritional Sciences Graduate Program, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
*
Address for correspondence: Troy A. Roepke, Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, 84 Lipman Drive, Bartlett Hall, New Brunswick, NJ 08901, USA. Email: ta.roepke@rutgers.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Maternal high-fat diet (HFD) alters hypothalamic programming and disrupts offspring energy homeostasis in rodents. We previously reported that the loss of ERα signaling partially blocks the effects of maternal HFD in female offspring fed a standard chow diet. In a companion study, we determined if the effects of maternal HFD were magnified by an adult obesogenic diet in our transgenic mouse models. Heterozygous ERα knockout (wild-type (WT)/KO) dams were fed a control breeder chow diet (25% fat) or a semipurified HFD (45% fat) 4 weeks prior to mating with heterozygous males (WT/KO or WT/ knockin) to produce WT, ERα KO, or ERα knockin/knockout (KIKO) (no estrogen response element (ERE) binding) female offspring, which were fed HFD for 20 weeks. Maternal HFD potentiated the effects of adult HFD on KIKO and KO body weight due to increased adiposity and decreased activity. Maternal HFD also produced KIKO females that exhibit KO-like insulin intolerance and impaired glucose homeostasis. Maternal HFD increased plasma interleukin 6 and monocyte chemoattractant protein 1 levels and G6pc and Pepck liver expression only in WT mice. Insulin and tumor necrosis factor α levels were higher in KO offspring from HFD-fed dams. Arcuate and liver expression of Esr1 was altered in KIKO and WT, respectively. These data suggest that loss of ERE-dependent ERα signaling, and not total ERα signaling, sensitizes females to the deleterious influence of maternal HFD on offspring energy and glucose potentially through the control of peripheral inflammation and hypothalamic and liver gene expression. Future studies will interrogate the tissue-specific mechanisms of maternal HFD programming through ERα signaling.

Keywords

Estrogen receptor αenergy homeostasisglucose homeostasisarcuate nucleusobesity
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 11 , Issue 3 , June 2020 , pp. 285 - 296
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

Current address: Jennifer A. Yang, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, San Diego, CA 92103, USA.

Kyle J. Mamounis, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.

References

Flegal, KM, Kruszon-Moran, D, Carroll, MD, Fryar, CD, Ogden, CL.Trends in obesity among adults in the United States, 2005 to 2014. JAMA. 2016; 315, 2284–2291.CrossRefGoogle ScholarPubMed
Barker, DJ, Bull, AR, Osmond, C, Simmonds, SJ.Fetal and placental size and risk of hypertension in adult life. BMJ. 1990; 301, 259–262.CrossRefGoogle ScholarPubMed
Howie, GJ, Sloboda, DM, Kamal, T, Vickers, MH.Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. J Physiol. 2009; 587, 905–915.CrossRefGoogle ScholarPubMed
Howie, GJ, Sloboda, DM, Reynolds, CM, Vickers, MH.Timing of maternal exposure to a high fat diet and development of obesity and hyperinsulinemia in male rat offspring: same metabolic phenotype, different developmental pathways? J Nutr Metab. 2013; 2013, 517384.CrossRefGoogle ScholarPubMed
Giraudo, SQ, Della-Fera, MA, Proctor, L, et al. Maternal high fat feeding and gestational dietary restriction: effects on offspring body weight, food intake and hypothalamic gene expression over three generations in mice. Pharmacol Biochem Behav. 2010; 97, 121–129.CrossRefGoogle ScholarPubMed
Samuelsson, AM, Matthews, PA, Jansen, E, Taylor, PD, Poston, L.Sucrose feeding in mouse pregnancy leads to hypertension, and sex-linked obesity and insulin resistance in female offspring. Front Physiol. 2013; 4, 14.CrossRefGoogle ScholarPubMed
Vogt, MC, Paeger, L, Hess, S, et al. Neonatal insulin action impairs hypothalamic neurocircuit formation in response to maternal high-fat feeding. Cell. 2014; 156, 495–509.CrossRefGoogle ScholarPubMed
Le Foll, C, Irani, BG, Magnan, C, Dunn-Meynell, A, Levin, BE.Effects of maternal genotype and diet on offspring glucose and fatty acid-sensing ventromedial hypothalamic nucleus neurons. Am J Physiol Regul Integr Comp Physiol. 2009; 297, R1351–R1357.CrossRefGoogle ScholarPubMed
Sanders, TR, Kim, DW, Glendining, KA, Jasoni, CL.Maternal obesity and IL-6 lead to aberrant developmental gene expression and deregulated neurite growth in the fetal arcuate nucleus. Endocrinology. 2014; 155, 2566–2577.CrossRefGoogle ScholarPubMed
Fahrenkrog, S, Harder, T, Stolaczyk, E, et al. Cross-fostering to diabetic rat dams affects early development of mediobasal hypothalamic nuclei regulating food intake, body weight, and metabolism. J Nutr. 2004; 134, 648–654.CrossRefGoogle ScholarPubMed
Bilbo, SD, Tsang, V.Enduring consequences of maternal obesity for brain inflammation and behavior of offspring. FASEB J. 2010; 24, 2104–2115.CrossRefGoogle ScholarPubMed
Marco, A, Kisliouk, T, Tabachnik, T, Meiri, N, Weller, A.Overweight and CpG methylation of the Pomc promoter in offspring of high-fat-diet-fed dams are not ‘reprogrammed’ by regular chow diet in rats. FASEB J. 2014; 28, 4148–4157.CrossRefGoogle Scholar
Cabanes, A, De Assis, S, Gustafsson, JA, Hilakivi-Clarke, L.Maternal high n-6 polyunsaturated fatty acid intake during pregnancy increases voluntary alcohol intake and hypothalamic estrogen receptor alpha and beta levels among female offspring. Dev Neurosci. 2000; 22, 488–493.CrossRefGoogle ScholarPubMed
Raygada, M, Cho, E, Hilakivi-Clarke, L.High maternal intake of polyunsaturated fatty acids during pregnancy in mice alters offsprings’ aggressive behavior, immobility in the swim test, locomotor activity and brain protein kinase C activity. J Nutr. 1998; 128, 2505–2511.Google ScholarPubMed
Hammes, SR, Levin, ER.Extranuclear steroid receptors: nature and actions. Endocr Rev. 2007; 28, 726–741.CrossRefGoogle ScholarPubMed
Qiu, J, Bosch, MA, Tobias, SC, et al. A G-protein-coupled estrogen receptor is involved in hypothalamic control of energy homeostasis. J Neurosci. 2006; 26, 5649–5655.CrossRefGoogle ScholarPubMed
Roepke, TA, Xue, C, Bosch, MA, et al. Genes associated with membrane-initiated signaling of estrogen and energy homeostasis. Endocrinology. 2008; 149, 6113–6124.CrossRefGoogle ScholarPubMed
Roepke, TA, Bosch, MA, Rick, EA, et al. Contribution of a membrane estrogen receptor to the estrogenic regulation of body temperature and energy homeostasis. Endocrinology. 2010; 151, 4926–4937.CrossRefGoogle ScholarPubMed
Levin, ER.Integration of the extranuclear and nuclear actions of estrogen. Mol Endocrinol. 2005; 19, 1951–1959.CrossRefGoogle ScholarPubMed
Vasudevan, N, Pfaff, DW.Membrane-initiated actions of estrogens in neuroendocrinology: Emerging principles. Endocr Rev. 2007; 28, 1–19.CrossRefGoogle ScholarPubMed
Ronnekleiv, O, Malyala, A, Kelly, M.Membrane-initiated signaling of estrogen in the brain. Semin Reprod Med. 2007; 25, 165–177.CrossRefGoogle Scholar
Yasrebi, A, Rivera, JA, Krumm, EA, Yang, JA, Roepke, TA.Activation of estrogen response element-independent ERα signaling protects female mice from diet-induced obesity. Endocrinology. 2017; 158, 319–334.CrossRefGoogle ScholarPubMed
Hewitt, SC, O’Brien, JE, Jameson, JL, Kissling, GE, Korach, KS.Selective disruption of ERα DNA-binding activity alters uterine responsiveness to estradiol. Mol Endocrinol. 2009; 23, 2111–2116.CrossRefGoogle Scholar
Couse, JF, Korach, KS.Estrogen receptor null mice: what have we learned and where will they lead us? Endocr Rev. 1999; 20, 358–417.CrossRefGoogle ScholarPubMed
Küppers, E, Krust, A, Chambon, P, Beyer, C.Functional alterations of the nigrostriatal dopamine system in estrogen receptor-α knockout (ERKO) mice. Psychoneuroendocrinology. 2008; 33, 832–838.CrossRefGoogle ScholarPubMed
Semaan, SJ, Kauffman, AS.Sexual differentiation and development of forebrain reproductive circuits. Curr Opin Neurobiol. 2010; 20, 424–431.CrossRefGoogle ScholarPubMed
Brannvall, K.Estrogen-receptor-dependent regulation of neural stem cell proliferation and differentiation. Mol Cell Neurosci. 2002; 21, 512–520.CrossRefGoogle ScholarPubMed
Roepke, TA, Yasrebi, A, Villalobos, A, et al. Loss of ERα partially reverses the effects of maternal high-fat diet on energy homeostasis in female mice. Sci Rep. 2017; 7, 6381.CrossRefGoogle ScholarPubMed
Hewitt, SC, Kissling, GE, Fieselman, KE, et al. Biological and biochemical consequences of global deletion of exon 3 from the ER alpha gene. FASEB J. 2010; 24, 4660–4667.Google ScholarPubMed
Hewitt, SC, Li, L, Grimm, SA, et al. Novel DNA motif binding activity observed in vivo with an estrogen receptor α mutant mouse. Mol Endocrinol. 2014; 28, 899–911.CrossRefGoogle ScholarPubMed
Sun, B, Purcell, RH, Terrillion, CE, et al. Maternal high-fat diet during gestation or suckling differentially affects offspring leptin sensitivity and obesity. Diabetes. 2012; 61, 2833–2841.CrossRefGoogle ScholarPubMed
Dunn, GA, Morgan, CP, Bale, TL.Sex-specificity in transgenerational epigenetic programming. Horm Behav. 2011; 59, 290–295.CrossRefGoogle ScholarPubMed
Pallarés, ME, Baier, CJ, Adrover, E, et al. Age-dependent effects of prenatal stress on the corticolimbic dopaminergic system development in the rat male offspring. Neurochem Res. 2013; 38, 2323–2335.CrossRefGoogle ScholarPubMed
Park, CJ, Zhao, Z, Glidewell-Kenney, C, et al. Genetic rescue of nonclassical ERα signaling normalizes energy balance in obese Erα-null mutant mice. J Clin Invest. 2011; 121, 604–612.Google ScholarPubMed
Jakacka, M, Ito, M, Martinson, F, et al. An estrogen receptor (ER)alpha deoxyribonucleic acid-binding domain knock-in mutation provides evidence for nonclassical ER pathway signaling in vivo. Mol Endocrinol. 2002; 16, 2188–2201.CrossRefGoogle ScholarPubMed
Mamounis, KJ, Yang, JA, Yasrebi, A, Roepke, TA.Estrogen response element-independent signaling partially restores post-ovariectomy body weight gain but is not sufficient for 17α-estradiol’s control of energy homeostasis. Steroids. 2014; 81, 88–98.CrossRefGoogle Scholar
Schmittgen, TD, Livak, KJ.Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008; 3, 1101–1108.CrossRefGoogle Scholar
Lam, YY, Ravussin, E.Indirect calorimetry: an indispensable tool to understand and predict obesity. Eur J Clin Nutr. 2016; 71, 318–322.CrossRefGoogle ScholarPubMed
Handgraaf, S, Riant, E, Fabre, A, et al. Prevention of obesity and insulin resistance by estrogens requires ERα activation function-2 (ERαAF-2), whereas ERαAF-1 is dispensable. Diabetes. 2013; 62, 4098–4108.CrossRefGoogle Scholar
Coll, AP, Farooqi, IS, O’Rahilly, S.The hormonal control of food intake. Cell. 2007; 129, 251–262.CrossRefGoogle ScholarPubMed
Nestor, CC, Qiu, J, Padilla, SL, et al. Optogenetic stimulation of arcuate nucleus Kiss1 neurons reveals a steroid-dependent glutamatergic input to POMC and AgRP neurons in male mice. Mol Endocrinol. 2016; 30, 630–644.CrossRefGoogle ScholarPubMed
Padilla, SL, Qiu, J, Nestor, CC, et al. AgRP to Kiss1 neuron signaling links nutritional state and fertility. Proc Natl Acad Sci U S A. 2017; 114, 2413–2418.CrossRefGoogle ScholarPubMed
Attig, L, Vige, A, Gabory, A, et al. Dietary alleviation of maternal obesity and diabetes: Increased resistance to diet-induced obesity transcriptional and epigenetic signatures. PLoS One. 2013; 8, e66816.CrossRefGoogle ScholarPubMed
Borengasser, SJ, Zhong, Y, Kang, P, et al. Maternal obesity enhances white adipose tissue differentiation and alters genome-scale DNA methylation in male rat offspring. Endocrinology. 2013; 154, 4113–4125.Google ScholarPubMed
Ashino, NG, Saito, KN, Souza, FD, et al. Maternal high-fat feeding through pregnancy and lactation predisposes mouse offspring to molecular insulin resistance and fatty liver. J Nutr Biochem. 2012; 23, 341–348.CrossRefGoogle ScholarPubMed
von Wilamowitz-Moellendorff, A, Hunter, RW, Garcia-Rocha, M, et al. Glucose-6-phosphate-mediated activation of liver glycogen synthase plays a key role in hepatic glycogen synthesis. Diabetes. 2013; 62, 4070–4082.CrossRefGoogle Scholar
Zammit, VA.Hepatic triacylglycerol synthesis and secretion: DGAT2 as the link between glycaemia and triglyceridaemia. Biochem J. 2013; 451, 1–12.CrossRefGoogle ScholarPubMed
Leonhardt, M, Langhans, W.Fatty acid oxidation and control of food intake. Physiol Behav. 2004; 83, 645–651.CrossRefGoogle ScholarPubMed
Strable, MS, Ntambi, JM.Genetic control of de novo lipogenesis: role in diet-induced obesity. Crit Rev Biochem Mol Biol. 2010; 45, 199–214.CrossRefGoogle ScholarPubMed
Flegal, KM, Carroll, MD, Kit, BK, Ogden, CL.Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA. 2012; 307, 491–497.CrossRefGoogle Scholar
Hales, CM, Fryar, CD, Carroll, MD, Freedman, DS, Ogden, CL.Trends in obesity and severe obesity prevalence in US youth and adults by sex and age, 2007-2008 to 2015-2016. JAMA. 2018; 319, 1723–1725.CrossRefGoogle ScholarPubMed
Ross, MG, Desai, M.Developmental programming of offspring obesity, adipogenesis, and appetite. Clin Obstet Gynecol. 2013; 56, 529–536.CrossRefGoogle ScholarPubMed
Sharp, GC, Salas, LA, Monnereau, C, et al. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium. Hum Mol Genet. 2017; 26, 4067–4085.CrossRefGoogle ScholarPubMed
Dunn, GA, Bale, TL.Maternal high-fat diet effects on third-generation female body size via the paternal lineage. Endocrinology. 2011; 152, 2228–2236.CrossRefGoogle ScholarPubMed
Massiera, F, Barbry, P, Guesnet, P, et al. A Western-like fat diet is sufficient to induce a gradual enhancement in fat mass over generations. J Lipid Res. 2010; 51, 2352–2361.CrossRefGoogle ScholarPubMed
Flowers, M, Sanek, N, Levine, J.Maternal phytoestrogen consumption programs body weight regulation by non-classical estrogen receptor alpha signaling in female offspring. Progr 96th Annu Meet Endocr Soc. Abstract MON-0932, 2014.Google Scholar
Jensen, MN, Ritskes-Hoitinga, M.How isoflavone levels in common rodent diets can interfere with the value of animal models and with experimental results. Lab Anim. 2007; 41, 1–18.CrossRefGoogle ScholarPubMed
Ruhlen, RL, Howdeshell, KL, Mao, J, et al. Low phytoestrogen levels in feed increase fetal serum estradiol resulting in the ‘fetal estrogenization syndrome’ and obesity in CD-1 mice. Environ Health Perspect. 2008; 116, 322–328.CrossRefGoogle Scholar
Shi, H, Seeley, RJ, Clegg, DJ.Sexual differences in the control of energy homeostasis. Front Neuroendocrinol. 2009; 30, 396–404.CrossRefGoogle ScholarPubMed
Cooke, PS, Naaz, A.Role of estrogens in adipocyte development and function. Exp Biol Med. 2004; 229, 1127–1135.CrossRefGoogle ScholarPubMed
Goyal, HO, Braden, TD, Williams, CS, et al. Exposure of neonatal male rats to estrogen induces abnormal morphology of the penis and loss of fertility. Reprod Toxicol. 2004; 18, 265–274.CrossRefGoogle Scholar
Wang, A, Luo, J, Moore, W, et al. GPR30 regulates diet-induced adiposity in female mice and adipogenesis in vitro. Sci Rep. 2016; 6, 34302.CrossRefGoogle ScholarPubMed
Riant, E, Waget, A, Cogo, H, et al. Estrogens protect against high-fat diet-induced insulin resistance and glucose intolerance in mice. Endocrinology. 2009; 150, 2109–2117.CrossRefGoogle ScholarPubMed
Xu, Y, Nedungadi, TP, Zhu, L, et al. Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metab. 2011; 14, 453–465.CrossRefGoogle ScholarPubMed
Johnson, S, Javurek, AB, Painter, MS, et al. Effects of a maternal high-fat diet on offspring behavioral and metabolic parameters in a rodent model. J Dev Orig Health Dis. 2017; 8, 75–88.CrossRefGoogle Scholar
Jelenik, T, Roden, M.How estrogens prevent from lipid-induced insulin resistance. Endocrinology. 2013; 154, 989–992.Google ScholarPubMed
Gorres, BK, Bomhoff, GL, Morris, JK, Geiger, PC.In vivo stimulation of oestrogen receptor α increases insulin-stimulated skeletal muscle glucose uptake. J Physiol. 2011; 589, 2041–2054.CrossRefGoogle ScholarPubMed
Barros, RPA, Gustafsson, J-Å.Estrogen receptors and the metabolic network. Cell Metab. 2011; 14, 289–299.CrossRefGoogle ScholarPubMed
Yonezawa, R, Wada, T, Matsumoto, N, et al. Central versus peripheral impact of estradiol on the impaired glucose metabolism in ovariectomized mice on a high-fat diet. Am J Physiol Endocrinol Metab. 2012; 303, E445–E456.CrossRefGoogle ScholarPubMed
Liu, J, Bisschop, PH, Eggels, L, et al. Intrahypothalamic estradiol regulates glucose metabolism via the sympathetic nervous system in female rats. Diabetes. 2013; 62, 435–443.CrossRefGoogle ScholarPubMed
Rother, E, Kuschewski, R, Alcazar, MA, et al. Hypothalamic JNK1 and IKKβ activation and impaired early postnatal glucose metabolism after maternal perinatal high-fat feeding. Endocrinology. 2012; 153, 770–781.CrossRefGoogle ScholarPubMed
Grayson, BE, Levasseur, PR, Williams, SM, et al. Changes in melanocortin expression and inflammatory pathways in fetal offspring of nonhuman primates fed a high-fat diet. Endocrinology. 2010; 151, 1622–1632.CrossRefGoogle ScholarPubMed
Gorski, JN, Dunn-Meynell, AA, Levin, BE.Maternal obesity increases hypothalamic leptin receptor expression and sensitivity in juvenile obesity-prone rats. Am J Physiol Regul Integr Comp Physiol. 2007; 292, R1782–R1791.CrossRefGoogle ScholarPubMed
Page, KC, Malik, RE, Ripple, JA, Anday, EK.Maternal and postweaning diet interaction alters hypothalamic gene expression and modulates response to a high-fat diet in male offspring. Am J Physiol Regul Integr Comp Physiol. 2009; 297, R1049–R1057.CrossRefGoogle ScholarPubMed
Chen, H, Simar, D, Morris, MJ.Hypothalamic neuroendocrine circuitry is programmed by maternal obesity: Interaction with postnatal nutritional environment. PLoS One. 2009; 4, e6259.CrossRefGoogle ScholarPubMed
Rajia, S, Chen, H, Morris, MJ.Maternal overnutrition impacts offspring adiposity and brain appetite markers-modulation by postweaning diet. J Neuroendocrinol. 2010; 22, 905–914.Google ScholarPubMed
Supplementary material: File

Roepke et al. supplementary material

Roepke et al. supplementary material

Download Roepke et al. supplementary material(File)
File 872.4 KB