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Sebastien G. Bouret

Associate Professor of Pediatrics

Sebastien G. Bouret

Research Topics

  • Hypothalamus
  • Development
  • Hormones
  • Neuroendocrinology
  • Obesity
  • Diabetes
  • Neurobiology

Research Images

Confocal image of a coronal section through a mouse hypothalamus showing axons from the arcuate nucleus (red fluorescence) innervating the paraventricular nucleus. These axons contain various neuropeptides involved in feeding and metabolism such as the anorexigenic neuropeptide alpha-MSH (green fluorescence) and the orexigenic neuropeptide beta-endorphin (blue fluorescence). These neural projections are known to convey signals from the adipocyte-derived hormone leptin to the paraventricular nucleus, which functions to regulate food intake and body weight throughout life.
Confocal image of a coronal section through a mouse hypothalamus showing axons from the arcuate nucleus (red fluorescence) innervating the paraventricular nucleus. These axons contain various neuropeptides involved in feeding and metabolism such as the anorexigenic neuropeptide alpha-MSH (green fluorescence) and the orexigenic neuropeptide beta-endorphin (blue fluorescence). These neural projections are known to convey signals from the adipocyte-derived hormone leptin to the paraventricular nucleus, which functions to regulate food intake and body weight throughout life.
Neuron proliferation in the embyonic hypothalamus. Both perinatal hormones (such as leptin) and nutrition appear to influence this biological process. This confocal image shows newly generated BrdU-positive cells (green fluorescence) in the neuroepithelium of an E12.5 embryo. Nuclei are depicted in blue, nestin-positive cell progenitors are shown in red.
Neuron proliferation in the embyonic hypothalamus. Both perinatal hormones (such as leptin) and nutrition appear to influence this biological process. This confocal image shows newly generated BrdU-positive cells (green fluorescence) in the neuroepithelium of an E12.5 embryo. Nuclei are depicted in blue, nestin-positive cell progenitors are shown in red.
DEXA scans of wild-type (left) and leptin-deficient (right) mice (see 2010 Lasker Award).  
Leptin is not only involved in body weight regulation, but also plays a key role, during both pre- and postnatal life, in the development of appetite-regulated pathways.
DEXA scans of wild-type (left) and leptin-deficient (right) mice (see 2010 Lasker Award). Leptin is not only involved in body weight regulation, but also plays a key role, during both pre- and postnatal life, in the development of appetite-regulated pathways.
Bouret's lab
Bouret's lab

Research Overview

The long-range goal of the Bouret's lab is to study the hormonal and molecular signals that direct development of hypothalamic feeding circuits. Our research has directly led to several breakthroughs in the understanding of the complex hormonal signals and neurodevelopmental substrates responsible for appetite regulation. Most notably, we found that metabolic hormones (such as leptin and ghrelin) influence the development and architecture of hypothalamic circuits involved in energy balance regulation. More recently, our lab has discovered a role for autophagy (a cellular process that degrades cytoplasmic materials, including organelles and misfolded proteins) in hypothalamic development and metabolic regulation. Our current research projects aim at determining the role of miRNAs and axon guidance molecules in hypothalamic development and how these biological processes contribute to lifelong metabolic regulation. Our current research goal is also to study the molecular signals that link postnatal overnutrition and the abnormal development of hypothalamic feeding circuits.

Contact Information

Mailing Address The Saban Research Institute
Children's Hospital of Los Angeles
Developmental Neuroscience Program
4650 Sunset Boulevard
MS 135
Los Angeles, CA 90027
Office Location CHLA 321
Office Phone (323) 361-8743
Lab Location The Saban Research Institute
Lab Phone
Fax (323) 361-1549
Office Location CHLA 321

Websites

Education

  • PhD 2001 Neuroscience - University of Lille, France
  • Postdoc fellow 2005 Neuroscience - Oregon Health and Science University

Selected Publications

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  • Coupe B, Ishii Y, Dietrich MO, Komatsu M, Horvath TL, Bouret SG. Loss of autophagy in proopiomelanocortin neurons perturbs axon growth and causes metabolic dysregulation. Cell Metabolism, 15(2):247-255, 2012
  • Bouret SG, Draper SJ, Simerly RB. Trophic action of leptin on hypothalamic neurons that regulate feeding. Science, 304(5667):108-110, 2004.
  • Caron E, Ciofi P, Prevot V, Bouret SG. Alteration in neonatal nutrition causes perturbations in hypothalamic neural circuits controlling reproductive function. The Journal of Neuroscience, 32(33): 1186-11494, 2012 (also This week in The Journal p. i)
  • Steculorum MS, Bouret SG. Maternal diabetes compromises the organization of hypothalamic feeding circuits and impairs leptin sensitivity in offspring. Endocrinology, 152(11): 4171-4179, 2011 (also News & Views p. 4007-4009)
  • Bouret SG, Bates SH, Chen S, Myers MG Jr., Simerly RB. Distinct roles for specific leptin receptor signals in the development of hypothalamic feeding circuits. The Journal of Neuroscience, 32(4):1244-1252, 2012 
  • Balland E, Dam J, Langlet F, Caron E, Steculorum S, Messina A, Rasika S, Falluel-Morel A, Anouar Y, Dehouck B, Trinquet E, Jockers R, Bouret SG, Prevot V. Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain. Cell Metabolism, 19(2):293-301 (also Cell Metabolism (Preview), 2014, 19(2): 173-175)., 2014.
  • Langlet F, Levin BE, Luquet S, Dunn-Meynell AA, Balland E, Lacombe E, Mazur D, Bouret SG, Prevot V, Dehouck B. Glucose and VEGF signaling promote blood-hypothalamus barrier plasticity and increase access of blood-borne molecules to the arcuate nucleus in response to fasting. Cell Metabolism, 2013, 17(4):607-617 (also Cell Metabolism (Preview), 2013, 17(4): 467-468). 
  • Coupe B, Bouret SG. Development of the hypothalamic melanocortin system. Frontiers in Endocrinology (Lausane), 4:38, 2013.
  • Bouret SG. Role of early hormonal and nutritional experiences in shaping feeding behavior and hypothalamic development. Journal of Nutrition, 140(3):653-657, 2010. 


  • Bouret SG. Organizational actions of metabolic hormones. Frontiers in Neuroendocrinology, 34(1):18-26, 2013 (cover article).