The incidence of preventable metabolic diseases in children has increased markedly over the past 2 decades. Currently, there is little information to determine the underlying causes or whether therapeutic or dietary interventions might be successful at preventing or reducing metabolic health risks in children from obese pregnancies. While studies in rodents have demonstrated that both maternal and perinatal nutritional environment is critical for normal development of the offspring, these are a short lived species with a different developmental pattern than primates. These studies will use a nonhuman primate (NHP) model to investigate the impact of poor maternal metabolic health and diet on the long-term health of the offspring up to adolescence. This will be the first study use a NHP model to investigate the long-term susceptibility to diet induced obesity and diabetes caused by poor maternal metabolic health and diet. For these studies, breeding NHPs will be chronically maintained on a diet high in fats and calories (HFD), similar to the typical American diet. The NHP is a critical model as it shares developmental features similar to human fetuses, especially in relationship to the brain. This proposal will focus on the impact on brain neurocircuitry that are critical for regulating energy expenditure as well as homeostatic and hedonic (reward) based feeding behavior. The hypothesis is that abnormalities in the development of this neurocircuitry lead to inappropriate metabolic compensatory responses to various metabolic challenges. Furthermore, we expect that HFD offspring will have a more potent drive to consume palatable and calorically dense foods. It is also hypothesized that these HFD offspring will display accelerated weight gain and insulin resistance when maintained chronically on a HFD during adolesecence, resulting in an early onset of metabolic complications (i.e., obesity and insulin resistance). Consumption of tasty and calorie dense foods is a major underlying cause of childhood obesity. These studies will determine if the drive to consume these foods is programmed during fetal development by the diet that the mother is consuming during pregnancy. Furthermore, these studies will identify potential long- term metabolic risks caused by this early reprogramming.

Public Health Relevance

Poor maternal health and nutrition are associated with an increased risk of metabolic diseases in children. However, the underlying complications and mechanisms that lead to the increase in obesity and diabetes in children are poorly understood. The NHP is a critical model to identify these mechanisms because of the similarities in development, as well as the structure and function of metabolic systems.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Integrative Physiology of Obesity and Diabetes Study Section (IPOD)
Program Officer
Silva, Corinne M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Oregon Health and Science University
Other Basic Sciences
Primate Centers
United States
Zip Code
True, Cadence; Arik, Anam; Lindsley, Sarah et al. (2018) Early High-Fat Diet Exposure Causes Dysregulation of the Orexin and Dopamine Neuronal Populations in Nonhuman Primates. Front Endocrinol (Lausanne) 9:508
True, Cadence; Dean, Tyler; Takahashi, Diana et al. (2018) Maternal High-Fat Diet Effects on Adaptations to Metabolic Challenges in Male and Female Juvenile Nonhuman Primates. Obesity (Silver Spring) 26:1430-1438
True, C; Takahashi, D; Kirigiti, M et al. (2017) Arcuate nucleus neuropeptide coexpression and connections to gonadotrophin-releasing hormone neurones in the female rhesus macaque. J Neuroendocrinol 29:
Kjaergaard, M; Nilsson, C; Secher, A et al. (2017) Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink. Nutr Diabetes 7:e242
Chadderdon, S M; Belcik, J T; Bader, L et al. (2016) Vasoconstrictor eicosanoids and impaired microvascular function in inactive and insulin-resistant primates. Int J Obes (Lond) 40:1600-1603
Chadderdon, Scott M; Belcik, J Todd; Bader, Lindsay et al. (2016) Temporal Changes in Skeletal Muscle Capillary Responses and Endothelial-Derived Vasodilators in Obesity-Related Insulin Resistance. Diabetes 65:2249-57
Juan De Solis, Alain; Baquero, Arian F; Bennett, Camdin M et al. (2016) Postnatal undernutrition delays a key step in the maturation of hypothalamic feeding circuits. Mol Metab 5:198-209
Rivera, Heidi M; Christiansen, Kelly J; Sullivan, Elinor L (2015) The role of maternal obesity in the risk of neuropsychiatric disorders. Front Neurosci 9:194
Sullivan, Elinor L; Holton, Kathleen F; Nousen, Elizabeth K et al. (2015) Early identification of ADHD risk via infant temperament and emotion regulation: a pilot study. J Child Psychol Psychiatry 56:949-57
Sullivan, Elinor L; Riper, Kellie M; Lockard, Rachel et al. (2015) Maternal high-fat diet programming of the neuroendocrine system and behavior. Horm Behav 76:153-61

Showing the most recent 10 out of 42 publications