Skip to main content

Adult offspring of high-fat diet-fed dams can have normal glucose tolerance and body composition

  • K. M. Platt (a1), R. J. Charnigo (a2) and K. J. Pearson (a1)

Maternal high-fat diet consumption and obesity have been shown to program long-term obesity and lead to impaired glucose tolerance in offspring. Many rodent studies, however, use non-purified, cereal-based diets as the control for purified high-fat diets. In this study, primiparous ICR mice were fed purified control diet (10–11 kcal% from fat of lard or butter origin) and lard (45 or 60 kcal% fat) or butter (32 or 60 kcal% fat)-based high-fat diets for 4 weeks before mating, throughout pregnancy, and for 2 weeks of nursing. Before mating, female mice fed the 32 and 60% butter-based high-fat diets exhibited impaired glucose tolerance but those females fed the lard-based diets showed normal glucose disposal following a glucose challenge. High-fat diet consumption by female mice of all groups decreased lean to fat mass ratios during the 4th week of diet treatment compared with those mice consuming the 10–11% fat diets. All females were bred to male mice and pregnancy and offspring outcomes were monitored. The body weight of pups born to 45% lard-fed dams was significantly increased before weaning, but only female offspring born to 32% butter-fed dams exhibited long-term body weight increases. Offspring glucose tolerance and body composition were measured for at least 1 year. Minimal, if any, differences were observed in the offspring parameters. These results suggest that many variables should be considered when designing future high-fat diet feeding and maternal obesity studies in mice.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Adult offspring of high-fat diet-fed dams can have normal glucose tolerance and body composition
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Adult offspring of high-fat diet-fed dams can have normal glucose tolerance and body composition
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Adult offspring of high-fat diet-fed dams can have normal glucose tolerance and body composition
      Available formats
The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution licence
Corresponding author
*Address for correspondence: K. J. Pearson, Graduate Center for Nutritional Sciences, College of Medicine, University of Kentucky, 900 South Limestone, Lexington, KY 40536-0200, USA. (Email
Hide All
1. Ogden, CL, Carroll, MD, Kit, BK, Flegal, KM. Prevalence of obesity in the United States, 2009–2010. NCHS Data Brief. 2012; 82, 18.
2. Cawley, J, Meyerhoefer, C. The medical care costs of obesity: an instrumental variables approach. J Health Econ. 2012; 31, 219230.
3. Wang, Y, Beydoun, MA, Liang, L, Caballero, B, Kumanyika, SK. Will all Americans become overweight or obese? Estimating the progression and cost of the US obesity epidemic. Obesity. 2008; 16, 23232330.
4. Kissebah, AH, Peiris, AN. Biology of regional body fat distribution: relationship to non-insulin-dependent diabetes mellitus. Diabetes Metab Rev. 1989; 5, 83109.
5. Balkau, B, Deanfield, JE, Despres, JP, et al. International Day for the Evaluation of Abdominal Obesity (IDEA): a study of waist circumference, cardiovascular disease, and diabetes mellitus in 168,000 primary care patients in 63 countries. Circulation. 2007; 116, 19421951.
6. Vahratian, A. Prevalence of overweight and obesity among women of childbearing age: results from the 2002 National Survey of Family Growth. Matern Child Health J. 2009; 13, 268273.
7. Hales, CN, Barker, DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia. 1992; 35, 595601.
8. Barker, DJ, Gluckman, PD, Godfrey, KM, et al. Fetal nutrition and cardiovascular disease in adult life. Lancet. 1993; 341, 938941.
9. Roseboom, T, de Rooij, S, Painter, R. The Dutch famine and its long-term consequences for adult health. Early Hum Dev. 2006; 82, 485491.
10. Tenenbaum-Gavish, K, Hod, M. Impact of maternal obesity on fetal health. Fetal Diagn Ther. 2013; 34, 17.
11. Whitaker, RC, Wright, JA, Pepe, MS, Seidel, KD, Dietz, WH. Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med. 1997; 337, 869873.
12. Gregorio, BM, Souza-Mello, V, Carvalho, JJ, Mandarim-de-Lacerda, CA, Aguila, MB. Maternal high-fat intake predisposes nonalcoholic fatty liver disease in C57BL/6 offspring. Am J Obstet Gynecol. 2010; 203, e491e498.
13. Lanham, SA, Roberts, C, Hollingworth, T, et al. Maternal high-fat diet: effects on offspring bone structure. Osteoporos Int. 2010; 21, 17031714.
14. Gniuli, D, Calcagno, A, Caristo, ME, et al. Effects of high-fat diet exposure during fetal life on type 2 diabetes development in the progeny. J Lipid Res. 2008; 49, 19361945.
15. Rother, E, Kuschewski, R, Alcazar, MA, et al. Hypothalamic JNK1 and IKKbeta activation and impaired early postnatal glucose metabolism after maternal perinatal high-fat feeding. Endocrinology. 2012; 153, 770781.
16. 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. Br J Nutr. 2007; 98, 843851.
17. White, CL, Purpera, MN, Morrison, CD. Maternal obesity is necessary for programming effect of high-fat diet on offspring. Am J Physiol Regul Integr Comp Physiol. 2009; 296, R1464R1472.
18. Buckley, AJ, Keseru, B, Briody, J, et al. Altered body composition and metabolism in the male offspring of high fat-fed rats. Metabolism. 2005; 54, 500507.
19. 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, 10971102.
20. Ornellas, F, Mello, VS, Mandarim-de-Lacerda, CA, Aguila, MB. Sexual dimorphism in fat distribution and metabolic profile in mice offspring from diet-induced obese mothers. Life Sci. 2013; 93, 454463.
21. Samuelsson, AM, Matthews, PA, Argenton, M, et al. Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension. 2008; 51, 383392.
22. Elahi, MM, Cagampang, FR, Mukhtar, D, et al. Long-term maternal high-fat feeding from weaning through pregnancy and lactation predisposes offspring to hypertension, raised plasma lipids and fatty liver in mice. Br J Nutr. 2009; 102, 514519.
23. Taylor, PD, McConnell, J, Khan, IY, et al. Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R134R139.
24. Ainge, H, Thompson, C, Ozanne, SE, Rooney, KB. A systematic review on animal models of maternal high fat feeding and offspring glycaemic control. Int J Obes (Lond). 2011; 35, 325335.
25. Nivoit, P, Morens, C, Van Assche, FA, et al. Established diet-induced obesity in female rats leads to offspring hyperphagia, adiposity and insulin resistance. Diabetologia. 2009; 52, 11331142.
26. Masuyama, H, Hiramatsu, Y. Effects of a high-fat diet exposure in utero on the metabolic syndrome-like phenomenon in mouse offspring through epigenetic changes in adipocytokine gene expression. Endocrinology. 2012; 153, 28232830.
27. Dunn, GA, Bale, TL. Maternal high-fat diet promotes body length increases and insulin insensitivity in second-generation mice. Endocrinology. 2009; 150, 49995009.
28. Chechi, K, Herzberg, GR, Cheema, SK. Maternal dietary fat intake during gestation and lactation alters tissue fatty acid composition in the adult offspring of C57Bl/6 mice. Prostaglandins Leukot Essent Fatty Acids. 2010; 83, 97104.
29. 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, 121129.
30. Gout, J, Sarafian, D, Mutel, E, et al. Metabolic and melanocortin gene expression alterations in male offspring of obese mice. Mol Cell Endocrinol. 2010; 319, 99108.
31. Hartil, K, Vuguin, PM, Kruse, M, et al. Maternal substrate utilization programs the development of the metabolic syndrome in male mice exposed to high fat in utero. Pediatr Res. 2009; 66, 368373.
32. Liang, C, Oest, ME, Prater, MR. Intrauterine exposure to high saturated fat diet elevates risk of adult-onset chronic diseases in C57BL/6 mice. Birth Defects Res B Dev Reprod Toxicol. 2009; 86, 377384.
33. Howie, GJ, Sloboda, DM, Kamal, T, Vickers, MH. Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. J Physiol. 2009; 587, 905915.
34. Srinivasan, M, Katewa, SD, Palaniyappan, A, Pandya, JD, Patel, MS. Maternal high-fat diet consumption results in fetal malprogramming predisposing to the onset of metabolic syndrome-like phenotype in adulthood. Am J Physiol Endocrinol Metab. 2006; 291, E792E799.
35. 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, 28332841.
36. Bieri, JG, Stoewsand, GS, Briggs, GM, Phillips, RW, Woodard, JC, Knapka, JJ. Report of the American Institute of Nutrition ad hoc Committee on standards for nutritional studies. J Nutr. 1977; 107, 13401348.
37. Reeves, PG. Components of the AIN-93 diets as improvements in the AIN-76A diet. J Nutr. 1997; 127, 838S841S.
38. Heindel, JJ, vom Saal, FS. Meeting report: batch-to-batch variability in estrogenic activity in commercial animal diets – importance and approaches for laboratory animal research. Environ Health Perspect. 2008; 116, 389393.
39. 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, 118.
40. Mead, MN. The feed factor: estrogenic variability in lab animal diets. Environ Health Perspect. 2006; 114, A640A642.
41. 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.
42. Douglas, G, Armitage, JA, Taylor, PD, et al. Cardiovascular consequences of life-long exposure to dietary isoflavones in the rat. J Physiol. 2006; 571, 477487.
43. Burton, JL, Wells, M. The effect of phytoestrogens on the female genital tract. J Clin Pathol. 2002; 55, 401407.
44. Chiang, SS, Pan, TM. Beneficial effects of phytoestrogens and their metabolites produced by intestinal microflora on bone health. Appl Microbiol Biotechnol. 2013; 97, 14891500.
45. Masilamani, M, Wei, J, Sampson, HA. Regulation of the immune response by soybean isoflavones. Immunol Res. 2012; 54, 95110.
46. Orgaard, A, Jensen, L. The effects of soy isoflavones on obesity. Exp Biol Med (Maywood). 2008; 233, 10661080.
47. Souzeau, E, Belanger, S, Picard, S, Deschepper, CF. Dietary isoflavones during pregnancy and lactation provide cardioprotection to offspring rats in adulthood. Am J Physiol Heart Circ Physiol. 2005; 289, H715H721.
48. Klein, SL, Wisniewski, AB, Marson, AL, Glass, GE, Gearhart, JP. Early exposure to genistein exerts long-lasting effects on the endocrine and immune systems in rats. Mol Med. 2002; 8, 742749.
49. Hilakivi-Clarke, L, Cho, E, Clarke, R. Maternal genistein exposure mimics the effects of estrogen on mammary gland development in female mouse offspring. Oncol Rep. 1998; 5, 609616.
50. Jefferson, WN, Padilla-Banks, E, Newbold, RR. Adverse effects on female development and reproduction in CD-1 mice following neonatal exposure to the phytoestrogen genistein at environmentally relevant doses. Biol Reprod. 2005; 73, 798806.
51. Sedova, L, Seda, O, Kazdova, L, et al. 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. 2007; 292, E1318E1324.
52. Platt, KM, Charnigo, RJ, Kincer, JF, Dickens, BJ, Pearson, KJ. Controlled exercise is a safe pregnancy intervention in mice. J Am Assoc Lab Anim Sci. 2013; 52, 524530.
53. Shimizu, R, Sakazaki, F, Okuno, T, Nakamuro, K, Ueno, H. Difference in glucose intolerance between C57BL/6J and ICR strain mice with streptozotocin/nicotinamide-induced diabetes. Biomed Res. 2012; 33, 6366.
54. Schlenker, E, Shi, Y, Johnson, C, Wipf, J. Acetazolamide affects breathing differently in ICR and C57 mice. Respir Physiol Neurobiol. 2006; 152, 119127.
55. Weizman, R, Paz, L, Backer, MM, et al. Mouse strains differ in their sensitivity to alprazolam effect in the staircase test. Brain Res. 1999; 839, 5865.
56. Miller, RA, Harrison, DE, Astle, CM, et al. An aging interventions testing program: study design and interim report. Aging Cell. 2007; 6, 565575.
57. Rebholz, SL, Jones, T, Burke, KT, et al. Multiparity leads to obesity and inflammation in mothers and obesity in male offspring. Am J Physiol Endocrinol Metab. 2012; 302, E449E457.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of Developmental Origins of Health and Disease
  • ISSN: 2040-1744
  • EISSN: 2040-1752
  • URL: /core/journals/journal-of-developmental-origins-of-health-and-disease
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Type Description Title
Supplementary materials

Platt Supplementary Material

 Word (24 KB)
24 KB


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed