Obesity Is a major public health problem worldwide and recent work has suggested that exposure to a suboptimal eariy environment may increase the risk of becoming obese. Epidemiological data show that an unfavorable intrauterine environment has long-term consequences in offspring including hypertension, cardiovascular disease, type 2 diabetes, obesity and neuropsychiatric disease. Specifically, prenatal stress and/or consumption of a high fat dieL characteristics of modern day human lifestyle, have been shown to lead to metabolic disorders such as obesity and Insulin resistance in offspring. However, the mechanisms involved are not well understood. The overall goal of this proposal is to characterize the short- and long-tenn effects of changes in the prenatal environment - stress and nutrition - on the behavioral and physiological development of offspring and to explore the possible neuropeptide and epigenetic mechanisms involved using a rat animal model.
Specific aims are: 1) To detemiine the developmental time course of behavioral and endocrine alterations resulting from prenatal stress. We will also test the hypothesis that prenatal stress will accentuate diet-induced obesity, Timepoints during lactation, adolescence, and adulthood will be examined to characterize the phenotype and to direct examination of possible mechanisms;2) To test the hypothesis that prenatal stress, high fat diet, or both result in alterations in neuropeptide systems regulating energy homeostasis that are consistent with other rodent models of obesity;and 3) To test the hypothesis that prenatal stress and nutrition results in obesity in offspring through epigenetic modifications via differential DNA methylation of genes that are critical to energy homeostasis. These experiments will enhance our understanding of the etiology of obesity and metabolic disease ultimately allowing the development of rational clinical interventions for such conditions.

Public Health Relevance

The prenatal environment plays a significant role in determining the health and well-being of offspring. This project will determine the effects of prenatal stress and maternal high fat diet on the metabolic phenotype of offspring. These studies will enable determination of the possible disease mechanisms involved in development of disease such as obesity and diabetes and provide information for establishment of more effective treatment ahd prevention strategies.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Transition Award (R00)
Project #
5R00HD055030-04
Application #
7754852
Study Section
Special Emphasis Panel (NSS)
Program Officer
Grave, Gilman D
Project Start
2007-10-01
Project End
2012-02-28
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
4
Fiscal Year
2010
Total Cost
$246,510
Indirect Cost
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Cordner, Zachary A; Tamashiro, Kellie L K (2015) Effects of high-fat diet exposure on learning & memory. Physiol Behav 152:363-71
Tamashiro, Kellie L K (2015) Developmental and environmental influences on physiology and behavior--2014 Alan N. Epstein Research Award. Physiol Behav 152:508-15
Lee, R S; Pirooznia, M; Guintivano, J et al. (2015) Search for common targets of lithium and valproic acid identifies novel epigenetic effects of lithium on the rat leptin receptor gene. Transl Psychiatry 5:e600
Boersma, Gretha J; Moghadam, Alexander A; Cordner, Zachary A et al. (2014) Prenatal stress and stress coping style interact to predict metabolic risk in male rats. Endocrinology 155:1302-12
Treesukosol, Yada; Boersma, Gretha J; Oros, Heather et al. (2014) Similarities and differences between ""proactive"" and ""passive"" stress-coping rats in responses to sucrose, NaCl, citric acid, and quinine. Chem Senses 39:333-42
Treesukosol, Yada; Sun, Bo; Moghadam, Alexander A et al. (2014) Maternal high-fat diet during pregnancy and lactation reduces the appetitive behavioral component in female offspring tested in a brief-access taste procedure. Am J Physiol Regul Integr Comp Physiol 306:R499-509
Ewald, Erin R; Wand, Gary S; Seifuddin, Fayaz et al. (2014) Alterations in DNA methylation of Fkbp5 as a determinant of blood-brain correlation of glucocorticoid exposure. Psychoneuroendocrinology 44:112-22
Boersma, G J; Bale, T L; Casanello, P et al. (2014) Long-term impact of early life events on physiology and behaviour. J Neuroendocrinol 26:587-602
Boersma, Gretha J; Lee, Richard S; Cordner, Zachary A et al. (2014) Prenatal stress decreases Bdnf expression and increases methylation of Bdnf exon IV in rats. Epigenetics 9:437-47
Sun, Bo; Liang, Nu-Chu; Ewald, Erin R et al. (2013) Early postweaning exercise improves central leptin sensitivity in offspring of rat dams fed high-fat diet during pregnancy and lactation. Am J Physiol Regul Integr Comp Physiol 305:R1076-84

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