This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The escalating prevalence of childhood obesity has profound health implications as it increases the risk of developing a number of serious diseases and decreases life expectancy. This laboratory has developed a primate model of high-fat diet (HFD) induced maternal obesity in which juvenile offspring have increased body weight, adiposity and evidence of fatty liver disease. Juvenile offspring also exhibit differences in food preference and heightened anxiety. In addition, we observe an increase in circulating and hypothalamic cytokines in fetal offspring during critical periods of development, suggesting that chronic maternal HFD consumption causes broad fetal lipotoxicity. Finally, we observe abnormalities in the development of the hypothalamic melanocortin system, a critical system for the regulation of energy homeostasis, in the fetal HFD offspring which likely contributes to the early onset obesity in these animals. As the serotonin (5-HT) system regulates energy balance primarily through modulation of the melanocortin system and is sensitive to early exposure to inflammatory cytokines, the overall hypothesis of this proposal is that maternal HFD consumption leads to early onset obesity due to perturbations in serotonergic signaling. This project determines that female offspring from HFD mothers have suppression of serotonergic tone which could contribute to increased risk for behavioral disorders such as anxiety and depression.
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