Obesity is an epidemic in the developed and developing world. The extent of this increase can be seen by the change in the incidence of obesity by state between 1990 and 2010.

cdc-us-obesity-trends

Developmental Programming as a cause of obesity.

Developmental programming is a response to a specific challenge to the fetus or baby during a critical developmental window that alters the trajectory of development with persistent effects on life-course health and predisposition to future disease.

Excess energy intake over expenditure is the ultimate cause of obesity. TPLH researchers (click here to read the full text) and others have shown that the drive to eat, which comes from our brain appetitive centers, is set during fetal development, influencing our energy intake. When an increased drive to eat is accompanied by increased food availability, especially of the high-calorie form in diets high in fat and carbohydrates, there is a lifetime of increased predisposition to obesity.

maternal-obesity-shortens-offspring-life-span
This graph shows that children of obese mothers with a high Body Mass Index (BMI), a standard measure of showing someone is overweight, live shorter lives than do children of mothers with normal BMI.

Obesity Research at the Texas Pregnancy and Life-course Health Research Center

The TPLH Research Center has an extensive collaboration with Dr. Elena Zambrano at the Mexican National Institute of Medical Sciences and Nutrition conducting studies in which we have shown that maternal obesity predisposes offspring to diabetes (Zambrano & Nathanielsz 2013Nutr Rev 71:S42-S54) and that exercise or maternal dietary intervention can be preventative (Nathanielsz et al. 2013 Nutr Rev 71:S78-S87). We are also working with Dr. Stephen Ford of University of Wyoming studying the adverse effects of maternal obesity on offspring in sheep.

Compared to humans, the normal rodent species have a very different metabolism and the maternal nutrient burden during pregnancy is much greater than in humans. With colleagues at the Southwest National Primate Research Center, we have developed a model of maternal obesity in the baboon and shown that maternal obesity leads to increased fibrosis in the fetal heart (Maloyan et al. 2013 Physiol Genomics 45:889-900).

Our aim is to determine the mechanisms that underlie the current explosion of obesity and diabetes.

In addition to predisposing offspring to obesity and diabetes, maternal obesity predisposes offspring to heart disease. The hearts of fetuses whose mothers are obese already show signs of developmental problems before birth.

fibrosis-staining-image
Hearts of fetuses of obese baboon mothers (left) show more fibrosis (blue stain) than do fetuses of lean mothers (right).

The cost to the nation of the epidemic of obesity.

The American Diabetes Association (ADA) estimates that the total cost to the nation of diabetes in 2012 was $245 billion: $176 billion in medical costs and $69 billion in reduced productivity– a 41% increase in 5 years.

Read more about the economic and personal cost of obesity and diabetes on the ADA website.

We are studying the function of the heart and appetite in baboons whose mothers were obese during pregnancy. The TPLH is a multi-institutional, multi-disciplinary program that makes available our unique nonhuman primate colony for collaborations with colleagues worldwide to evaluate:

  1. effects of obesity on health of mothers and complications of pregnancy;
  2. outcomes of developmental programming by maternal over-nutrition,
  3. how offspring of obese mothers live shorter lives.

If you have an interest in participating, contact the Director, Peter W Nathanielsz, at ude.o1495467524ywu@z1495467524slein1495467524ahtaN1495467524.rete1495467524P1495467524.

Selected Publications:

  1. Long, N. M., Rule, D. C., Tuersunjiang, N., Nathanielsz, P. W., & Ford, S. P. (2015) Maternal obesity in sheep increases fatty acid synthesis, upregulates nutrient transporters, and increases adiposity in adult male offspring after a feeding challenge. PloS One 10(4): e0122152. PMID 25875659.
  2. Rodríguez-González, G. L., Vega, C. C., Boeck, L., Vázquez, M., Bautista, C. J., Reyes-Castro, L. A., Saldaña O., Lovera, D., Nathanielsz, P. W., Zambrano, E. (2015) Maternal obesity and overnutrition increase oxidative stress in male rat offspring reproductive system and decrease fertility. Int J Obes (Lond) 39(4): 549–556. PMID 25504042.
  3. Shasa, D. R., Odhiambo, J. F., Long, N. M., Tuersunjiang, N., Nathanielsz, P. W., & Ford, S. P. (2015) Multigenerational impact of maternal overnutrition/obesity in the sheep on the neonatal leptin surge in granddaughters. Int J Obes (Lond) 39(4): 695–701. PMID 25354845.
  4. Dong, M., Zheng, Q., Ford, S. P., Nathanielsz, P. W., & Ren, J. (2013) Maternal obesity, lipotoxicity and cardiovascular diseases in offspring. J Mol Cell Cardiol 55, 111–116. PMID 22982026.
  5. Li C, McDonald TJ, Wu G, Nijland MJ, Nathanielsz PW. Intrauterine growth restriction alters term fetal baboon hypothalamic appetitive peptide balance. J Endocrinol2013;217(3):275-282. PMID 23482706.
  6. Maloyan, A., Muralimanoharan, S., Huffman, S., Cox, L.A., Nathanielsz, P.W., Myatt, L., Nijland, M.J. (2013) Identification and Comparative Analyses of Myocardial miRNAs Involved in the Fetal Response to Maternal Obesity. Physiol Genomics 45(19): 889-900. PMID 23922128.
  7. Nathanielsz, P.W., Ford, S.P., Long, N.M., Vega, C.C., Reyes-Castro, L.A. and Zambrano, E. (2013) Interventions to prevent adverse fetal programming due to maternal obesity during pregnancy. Nutr Rev 71 Suppl 1, S78-S87. PMID 24147928.
  8. Zambrano, E., Nathanielsz, P.W. (2013) Mechanisms by which maternal obesity programs offspring for obesity: evidence from animal studies. Nutr Rev 71(Suppl 1): S42-S54. PMID 24147924.
  9. Huang, Y., Zhao, J.X., Yan, X., Zhu, M.J., Long, N.M., McCormick, R.J., Ford, S.P., Nathanielsz, P.W., Du, M. (2012) Maternal obesity enhances collagen accumulation and cross-linking in skeletal muscle of ovine offspring. PLoS One 7: e31691. PMID 22348119.
  10. Long, N.M., Nathanielsz, P.W., Ford, S.P. (2012) The impact of maternal overnutrition and obesity on hypothalamic-pituitary-adrenal axis response of offspring to stress. Domest Anim Endocrinol 42(4): 195–202. PMID 22264661.
  11. Long, N.M., Rule, D.C., Zhu, M.J., Nathanielsz, P.W., Ford, S.P. (2012) Maternal obesity upregulates fatty acid and glucose transporters and increases expression of enzymes mediating fatty acid biosynthesis in fetal adipose tissue depots. J Anim Sci 90(7): 2201-2210. PMID 22266999.
  12. Rodriguez, J.S., Rodríguez-González, G.L., Reyes-Castro, L.A., Ibáñez, C., Ramírez, A., Chavira, R., Larrea, F., Nathanielsz, P.W. and Zambrano, E. (2012) Maternal obesity in the rat programs male offspring exploratory, learning and motivation behavior: prevention by dietary intervention pre-gestation or in gestation. Int J Dev Neurosci 30: 75-81. PMID 22239918.
  13. Yan, X., Huang, Y., Zhao, J.X., Rogers, C.J., Zhu, M.J., Ford, S.P., Nathanielsz, P.W., Du, M. (2012) Maternal obesity downregulates microRNA let-7g expression, a possible mechanism for enhanced adipogenesis during ovine fetal skeletal muscle development. Int J Obes (Lond) 37(4): 568-575. PMID 22614057.
  14. Long NM, Ford SP, Nathanielsz PW. (2011) Maternal obesity eliminates the neonatal lamb plasma leptin peak. J Physiol 589(6): 1455–1462. PMID 21262878.
  15. Yan X, Huang Y, Wang H, Du M, Hess BW, Ford SP, Nathanielsz PW, Zhu MJ. (2011) Maternal obesity induces sustained inflammation in both fetal and offspring large intestine of sheep. Inflamm Bowel Dis 17(7): 1513-22. PMID 21674707.
  16. Yan, X, Huang Y, Zhao JX, Long NM, Uthlaut AB, Zhu MJ, Ford SP, Nathanielsz PW, Du M (2011) Maternal Obesity-Impaired Insulin Signaling in Sheep and Induced Lipid Accumulation and Fibrosis in Skeletal Muscle of Offspring. Biol Reprod 85(1): 172-178. PMID 21349823.
  17. Zhang L, Long NM, Hein SM, Ma Y, Nathanielsz PW, Ford SP. (2011) Maternal obesity in ewes results in reduced fetal pancreatic β-cell numbers in late gestation and decreased circulating insulin concentration at term. Domest Anim Endocrinol 40(1): 30-9. PMID 20933362.
  18. Farley D.M., Choi J., Dudley D.J., Li C., Jenkins S.L., Myatt L., Nathanielsz P.W. (2010) Placental amino acid transport and placental leptin resistance in pregnancies complicated by maternal obesity. Placenta 31(8): 718-24. PMID 20609473.
  19. Huang Y, Yan X, Zhao JX, Zhu MJ, McCormick RJ, Ford SP, Nathanielsz PW, Ren J, Du M. (2010) Maternal obesity induces fibrosis in fetal myocardium of sheep. Am J Physiol Endocrinol Metab 299(6): E968-75. PMID 20876759.
  20. Long NM, George LA, Uthlaut AB, Smith DT, Nijland MJ, Nathanielsz PW, Ford SP. (2010) Maternal obesity and increased nutrient intake before and during gestation in the ewe results in altered growth, adiposity and glucose tolerance in adult offspring. J Anim Sci 88(11): 3546-53. PMID 20622177.