Prader-Willi syndrome (PWS) is a genetic disease characterized by an insatiable appetite and a variety or behavioral dysregulations. It is known that the brain, and particularly a region of the brain called the hypothalamus, is important to regulating appetite and body weight. We also know that many key physiological processes, including appetite regulation, are established during the perinatal period, that time just prior to and soon after birth. We previously found that the development of neurons that cause satiety is attenuated in a mouse model for PWS. Using mouse models, this research project will investigate the specific cellular mechanisms that are responsible for the loss of satiety signals in PWS. We will also test whether intervening with this cellular pathway will ameliorate the nerve cell deficits observed PWS. Understanding of the impairments in the brain cells that cause satiety is critical for designing treatments and cures for PWS. The knowledge we gain from this project may therefore help identify therapeutic targets to reduce the insatiable appetite associated with PWS.
This project is in loving memory of baby Violet Ai Xin Hasenmyer, a life that was lost too soon, but a life that was not without purpose or joy.
Research Outcomes:Wired for eating: how is an active feeding circuitry established in the postnatal brain? Muscatelli F, Bouret SGC. Current Opinion in Neurobiology. Volume 52: 165-171, 2018.
Sex and gender differences in developmental programming of metabolism. Dearden L, Bouret SG, Ozanne SE. Molecular Metabolism. 15: 8–19, 2018.
A Transcriptomic Signature of the Hypothalamic Response to Fasting and BDNF Deficiency in Prader-Willi Syndrome. Bochukova EG, Lawler K, Croizier S, Keogh JM, Patel N, Strohbehn G, Lo KK, Humphrey J, Hokken-Koelega A, Damen L, Donze S, Bouret SG, Plagnol V, Farooqi IS. Cell Reports. 2018 Mar 27; 22(13): 3401–3408.
Loss of Magel2 Impairs the Development of Hypothalamic Anorexigenic Circuits. Maillard J, Park S, Croizier S, Vanacker C, Cook JH, Prevot V, Tauber M, Bouret SG. Human Molecular Genetics. 2016 Aug 1;25(15):3208-3215.
Obesity Impairs the Action of the Neuroendocrine Ghrelin System. Zigman JM, Bouret SG, Andrews ZB. Trends Endocrinol Metab. 2016 Jan;27(1):54-63.
Neonatal ghrelin programs development of hypothalamic feeding circuits. Steculorum SM, Collden G, Coupe B, Croizier S, Lockie S, Andrews ZB, Jarosch F, Klussmann S, Bouret SG. Journal of Clinical Investigation. 2015 Feb 2;125(2):846-58.
Gene-Environment Interactions Controlling Energy and Glucose Homeostasis and the Developmental Origins of Obesity. Bouret S, Levin BE, Ozanne SE. Physiol Rev. 2015 Jan;95(1):47-82.
Neonatal overnutrition causes early alterations in the central response to peripheral ghrelin. Collden G, Balland E, Parkash J, Caron E, Langlet F, Prevot V, Bouret SG. Mol Met. 2015 Jan 4(1):15–24.
Development of the hypothalamic melanocortin system. Coupe B, Bouret SG. Frontiers in Endocrinology (Lausanne). 2013;4:38.
Sebastien Bouret, PhD
Children’s Hospital Los Angeles