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Cited by 923Birth, Development, and HealthDiet, Metabolism, and DiseaseAdipokines, Inflammation, and Metabolic Diseases

Diet-Induced Obesity in Female Mice Leads to Offspring Hyperphagia, Adiposity, Hypertension, and Insulin Resistance: A Novel Murine Model of Developmental Programming

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Samuelsson, Anne-Maj, Matthews, Phillippa A., Argenton, Marco, Christie, Michael R., McConnell, Josie M., Jansen, Eugene H.J. M., Piersma, Aldert H., Ozanne, Susan E. +5 more·2008·Hypertension
DOI 10.1161/hypertensionaha.107.101477
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Abstract

Maternal obesity is increasingly prevalent and may affect the long-term health of the child. We investigated the effects of maternal diet-induced obesity in mice on offspring metabolic and cardiovascular function. Female C57BL/6J mice were fed either a standard chow (3% fat, 7% sugar) or a palatable obesogenic diet (16% fat, 33% sugar) for 6 weeks before mating and throughout pregnancy and lactation. Offspring of control (OC) and obese dams (OO) were weaned onto standard chow and studied at 3 and 6 months of age. OO were hyperphagic from 4 to 6 weeks of age compared with OC and at 3 months locomotor activity was reduced and adiposity increased (abdominal fat pad mass; P <0.01). OO were heavier than OC at 6 months (body weight, P <0.05). OO abdominal obesity was associated with adipocyte hypertrophy and altered mRNA expression of β-adrenoceptor 2 and 3, 11βHSD-1, and PPAR-γ 2. OO showed resistance artery endothelial dysfunction at 3 months, and were hypertensive, as assessed by radiotelemetry (nighttime systolic blood pressure at 6 months [mm Hg] mean±SEM, male OO, 134±1 versus OC, 124±2, n=8, P <0.05; female OO, 137±2 versus OC, 122±4, n=8, P <0.01). OO skeletal muscle mass ( tibialis anterior ) was significantly reduced ( P <0.01) OO fasting insulin was raised at 3 months and by 6 months fasting plasma glucose was elevated. Exposure to the influences of maternal obesity in the developing mouse led to adult offspring adiposity and cardiovascular and metabolic dysfunction. Developmentally programmed hyperphagia, physical inactivity, and altered adipocyte metabolism may play a mechanistic role.

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  • Several studies have reported impaired vascular function between three and six months of age in arteries isolated from rat offspring of obese dams.

    “Several studies have reported elevated blood pressure as well as vascular remodeling and impaired vascular function between three and six months of age in arteries isolated from rat offspring of obese dams [94,100,126,127].”

    From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [94]

    The Resistance Artery Function section reports impaired acetylcholine-induced relaxation in isolated arteries from offspring of obese dams at 3 months, but the offspring were mice, not rats. It also says artery function was similar between groups at 6 months, so this paper does not support impairment throughout the stated age range. Page numbers were not provided in our copy. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Several studies have reported elevated blood pressure between three and six months of age in arteries isolated from rat offspring of obese dams.

    “Several studies have reported elevated blood pressure as well as vascular remodeling and impaired vascular function between three and six months of age in arteries isolated from rat offspring of obese dams [94,100,126,127].”

    From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [94]

    The Abstract and Blood Pressure, Heart Rate, and Activity section (page not supplied) report elevated blood pressure in offspring of obese dams, particularly at six months. But this study examined mice, not rats, and measured blood pressure by radiotelemetry, not in isolated arteries. The isolated-artery tests assessed vascular function at three months. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • Pregnant obese mice fed a high-fat diet supplemented with sweetened condensed milk were hyperinsulinemic, but without hyperglycemia.

    “These pregnant, obese mice were hyperinsulinemic, but without hyperglycemia [94].”

    From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [94]

  • At weaning (21 days after birth), obese dams were both hyperglycemic and hyperinsulinemic, compared to standard chow-fed dams.

    “At weaning (21 days after birth), these obese dams were both hyperglycemic and hyperinsulinemic, compared to standard chow-fed dams [94].”

    From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [94]

  • Several studies have reported vascular remodeling between three and six months of age in arteries isolated from rat offspring of obese dams.

    “Several studies have reported elevated blood pressure as well as vascular remodeling and impaired vascular function between three and six months of age in arteries isolated from rat offspring of obese dams [94,100,126,127].”

    From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [94]

    The Resistance Artery Function section reports altered responses in isolated arteries from mouse offspring at 3 months, but does not report vascular remodeling in rat offspring. The Discussion mentions raised blood pressure in rats from an earlier study, not remodeling; a search for remodeling and arterial structure found no passage supporting the attributed claim. Page numbers were unavailable in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 34

  1. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999 -2002. JAMA. 2004;291:2847-2850.
  2. Catalano PM, Ehrenberg HM. The short-and long-term implications of maternal obesity on the mother and her offspring. Bjog. 2006;113: 1126 -1133.
  3. Levin BE. Metabolic imprinting: critical impact of the perinatal envi- ronment on the regulation of energy homeostasis. Philosophical Trans- actions of the Royal Society of London. 2006;361:1107-1121.
  4. Armitage JA, Khan IY, Taylor PD, Nathanielsz PW, Poston L. Develop- mental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals? J Physiol. 2004;561:355-377.
  5. Zhang J, Wang C, Terroni PL, Cagampang FR, Hanson M, Byrne CD. High-unsaturated-fat, high-protein, and low-carbohydrate diet during pregnancy and lactation modulates hepatic lipid metabolism in female adult offspring. Am J Physiol Regul Integr Comp Physiol. 2005;288: R112-R118.
  6. Desai M, Gayle D, Han G, Ross MG. Programmed hyperphagia due to reduced anorexigenic mechanisms in intrauterine growth-restricted off- spring. Reproductive sciences (Thousand Oaks, Calif). 2007;14:329 -337.
  7. Lambin S, van Bree R, Caluwaerts S, Vercruysse L, Vergote I, Verhaeghe J. Adipose tissue in offspring of Lepr(db/ϩ) mice: early-life environment vs. genotype. Am J Physiol Endocrinol Metab. 2007;292:E262-E271.
  8. Cambonie G, Comte B, Yzydorczyk C, Ntimbane T, Germain N, Le NL, Pladys P, Gauthier C, Lahaie I, Abran D, Lavoie JC, Nuyt AM. Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and micro- vascular rarefaction associated with in utero exposure to a low-protein diet. Am J Physiol. 2007;292:R1236 -R1245.
  9. Khan IY, Taylor PD, Dekou V, Seed PT, Lakasing L, Graham D, Dominiczak AF, Hanson MA, Poston L. Gender-linked hypertension in offspring of lard-fed pregnant rats. Hypertension. 2003;41:168 -175.
  10. Rosenblatt JD, Kuzon WM Jr, Plyley MJ, Pynn BR, McKee NH. A histochemical method for the simultaneous demonstration of capillaries and fiber type in skeletal muscle. Stain Technology. 1987;62:85-92.
  11. Lobner K, Steinbrenner H, Roberts GA, Ling Z, Huang GC, Piquer S, Pipeleers DG, Seissler J, Christie MR. Different regulated expression of the tyrosine phosphatase-like proteins IA-2 and phogrin by glucose and insulin in pancreatic islets: relationship to development of insulin secretory responses in early life. Diabetes. 2002;51:2982-2988.
  12. Etherton TD, Thompson EH, Allen CE. Improved techniques for studies of adipocyte cellularity and metabolism. J Lipid Res. 1977;18:552-557.
  13. Siemelink M, Verhoef A, Dormans JA, Span PN, Piersma AH. Dietary fatty acid composition during pregnancy and lactation in the rat programs growth and glucose metabolism in the offspring. Diabetologia. 2002;45: 1397-1403.
  14. Khan I, Dekou V, Hanson M, Poston L, Taylor P. Predictive adaptive responses to maternal high-fat diet prevent endothelial dysfunction but not hypertension in adult rat offspring. Circulation. 2004;110:1097-1102.
  15. Korotkova M, Gabrielsson BG, Holmang A, Larsson BM, Hanson LA, Strandvik B. Gender-related long-term effects in adult rats by perinatal dietary ratio of n-6/n-3 fatty acids. Am J Physiol Regul Integr Comp Physiol. 2005;288:R575-R579.
  16. Gregersen S, Dyrskog SE, Storlien LH, Hermansen K. Comparison of a high saturated fat diet with a high carbohydrate diet during pregnancy and lactation: effects on insulin sensitivity in offspring of rats. Metabolism. 2005;54:1316 -1322.
  17. Surwit RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN. Diet- induced type II diabetes in C57BL/6J mice. Diabetes. 1988;37: 1163-1167.
  18. Napoli C, de Nigris F, Welch JS, Calara FB, Stuart RO, Glass CK, Palinski W. Maternal hypercholesterolemia during pregnancy promotes early atherogenesis in LDL receptor-deficient mice and alters aortic gene expression determined by microarray. Circulation. 2002;105:1360 -1367.
  19. Guo F, Jen KL. High-fat feeding during pregnancy and lactation affects offspring metabolism in rats. Physiol Behavior. 1995;57:681-686.
  20. Buckley AJ, Keseru B, Briody J, Thompson M, Ozanne SE, Thompson CH. Altered body composition and metabolism in the male offspring of high fat-fed rats. Metabolism. 2005;54:500 -507.
  21. Ferezou-Viala J, Roy AF, Serougne C, Gripois D, Parquet M, Bailleux V, Gertler A, Delplanque B, Djiane J, Riottot M, Taouis M. Long-term consequences of maternal high-fat feeding on hypothalamic leptin sensi- tivity and diet-induced obesity in the offspring. Am J Physiol. 2007;293: R1056 -R1062.
  22. Yamashita H, Shao J, Qiao L, Pagliassotti M, Friedman JE. Effect of spontaneous gestational diabetes on fetal and postnatal hepatic insulin resistance in Lepr(db/ϩ) mice. Pediatr Res. 2003;53:411-418.
  23. Gorski JN, Dunn-Meynell AA, Levin BE. Maternal obesity increases hypothalamic leptin receptor expression and sensitivity in juvenile obesity-prone rats. Am J Physiol. 2007;292:R1782-R1791.
  24. Bayol SA, Farrington SJ, Stickland NC. A maternal 'junk food' diet in pregnancy and lactation promotes an exacerbated taste for 'junk food' and a greater propensity for obesity in rat offspring. Brit J Nutr. 2007;98: 843-851.
  25. Plagemann A. Perinatal programming and functional teratogenesis: Impact on body weight regulation and obesity. Physiol Behavior. 2005; 86:661-668.
  26. Franke K, Harder T, Aerts L, Melchior K, Fahrenkrog S, Rodekamp E, Ziska T, Van Assche FA, Dudenhausen JW, Plagemann A. 'Pro- gramming' of orexigenic and anorexigenic hypothalamic neurons in off- spring of treated and untreated diabetic mother rats. Brain Res. 2005; 1031:276 -283.
  27. Yura S, Itoh H, Sagawa N, Yamamoto H, Masuzaki H, Nakao K, Kawamura M, Takemura M, Kakui K, Ogawa Y, Fujii S. Role of pre- mature leptin surge in obesity resulting from intrauterine undernutrition. Cell Metab. 2005;1:371-378.
  28. Vickers MH, Breier BH, McCarthy D, Gluckman PD. Sedentary behavior during postnatal life is determined by the prenatal environment and exacerbated by postnatal hypercaloric nutrition. Am J Physiol Regul Integr Comp Physiol. 2003;285:R271-R273.
  29. Bayol SA, Simbi BH, Stickland NC. A maternal cafeteria diet during gestation and lactation promotes adiposity and impairs skeletal muscle development and metabolism in rat offspring at weaning. J Physiol. 2005;567:951-961.
  30. Vidal-Puig AJ, Considine RV, Jimenez-Linan M, Werman A, Pories WJ, Caro JF, Flier JS. Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regu- lation by insulin and glucocorticoids. J Clin Invest. 1997;99:2416 -2422.
  31. Hausman DB, DiGirolamo M, Bartness TJ, Hausman GJ, Martin RJ. The biology of white adipocyte proliferation. Obes Rev. 2001;2:239 -254.
  32. Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS. A transgenic model of visceral obesity and the metabolic syndrome. Science NY. 2001;294:2166 -2170.
  33. Taylor PD, McConnell J, Khan IY, Holemans K, Lawrence KM, Asare-Anane H, Persaud SJ, Jones PM, Petrie L, Hanson MA, Poston L. Impaired glucose homeostasis and mitochondrial abnormalities in off- spring of rats fed a fat-rich diet in pregnancy. Am J Physiol Regul Integr Comp Physiol. 2005;288:R134 -R139.
  34. Srinivasan M, Aalinkeel R, Song F, Mitrani P, Pandya JD, Strutt B, Hill DJ, Patel MS. Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype. Am J Physiol Endocrinol Metab. 2006;290:E129 -E134.

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Authors
Samuelsson, A.-M., Matthews, P. A., Argenton, M., Christie, M. R., McConnell, J. M., Jansen, E. H. J. M., Piersma, A. H., Ozanne, S. E., Twinn, D. F., Remacle, C., Rowlerson, A., Poston, L., & Taylor, P. D.
Affiliations
  • King's College London (GB)
  • From the Division of Reproduction &amp; Endocrinology (A.-M.S., P.A.M., M.A., M.R.C., J.M.M., L.P., P.D.T.) and Applied Biomedical Research Group (A.R.), King’s College London, UK; the Laboratory for Health Protection Research (E.H.J.M.J., A.H.P.), National Institute for Public Health and the Environment, Bilthoven, Netherlands; the Department of Clinical Biochemistry (S.E.O., D.F.T.), University of Cambridge, UK; and the Institute of Life Sciences (C.R.), Université Catholique de Louvain, Louvain...
ORCID
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2008-02
Volume
51
Issue
2
Pages
383-392
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/hypertensionaha.107.101477
OpenAlex
W2083321610
Cited by
923
References
4
Citations by year
2026: 13 · 2025: 24 · 2024: 40 · 2023: 39 · 2022: 48 · 2021: 43 · 2020: 43 · 2019: 57 · 2018: 61 · 2017: 45 · 2016: 71 · 2015: 63 · 2014: 73 · 2013: 83 · 2012: 54
FWCI
33.13
Type
journal article
Language
en
Open access
Locations
  • Hypertension (publishedVersion)
  • PubMed (publishedVersion)
  • DIAL (Catholic University of Leuven) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Research Portal (King's College London) (submittedVersion)
  • Rivm (National Institute for Public Health and the Environment) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
maternal obesity, diet-induced obesity, offspring metabolic programming, hyperphagia, adiposity, insulin resistance, adipocyte hypertrophy, beta-adrenergic receptors, PPARγ, endothelial dysfunction, skeletal muscle mass, locomotor activity, obesogenic diet, developmental programming
MeSH terms
Animals, Arteries, Blood Pressure, Capillaries, Diet, Female, Glucose Tolerance Test, Heart Rate, Hyperphagia, Hypertension, Insulin, Insulin Resistance, Male, Mice, Inbred C57BL, Obesity, Pancreas, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, Vascular Resistance, Gene Expression, Adipocytes, Cell Size, Adiposity, Mice

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