Faculty

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Sebastien G. Bouret, PhD
Associate Professor of Pediatrics
Pediatrics
CHL Mail Stop 135 Off Campus Los Angeles
+1 323 361 8743

Overview

The long-range goal of the Bouret's lab is to study the hormonal and molecular signals that direct development of brain feeding circuits. Research in the Bouret’s lab 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 examining the cellular (e.g., ER stress and autophagy) and molecular (e.g., miRNAs, axon guidance cues) events involved in hypothalamic development and lifelong metabolic regulation. Our current research goal is also to study the molecular signals that link nmaternal obesity and the abnormal development of hypothalamic feeding circuits.

Publications

Loss of Magel2 impairs the development of hypothalamic Anorexigenic circuits. Hum Mol Genet. 2016 Aug 01; 25(15):3208-3215. View in: PubMed

Correction to 'Obesity Impairs the Action of the Neuroendocrine Ghrelin System': [Trends in Endocrinology and Metabolism, 27 (2016) 54-63]. Trends Endocrinol Metab. 2016 May; 27(5):348. View in: PubMed

Leptin Controls Parasympathetic Wiring of the Pancreas during Embryonic Life. Cell Rep. 2016 Apr 5; 15(1):36-44. View in: PubMed

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016 Jan 2; 12(1):1-222. View in: PubMed

Obesity Impairs the Action of the Neuroendocrine Ghrelin System. Trends Endocrinol Metab. 2016 Jan; 27(1):54-63. View in: PubMed

Neonatal ghrelin programs development of hypothalamic feeding circuits. J Clin Invest. 2015 Feb 2; 125(2):846-58. View in: PubMed

Neonatal overnutrition causes early alterations in the central response to peripheral ghrelin. Mol Metab. 2015 Jan; 4(1):15-24. View in: PubMed

Gene-environment interactions controlling energy and glucose homeostasis and the developmental origins of obesity. Physiol Rev. 2015 Jan; 95(1):47-82. View in: PubMed

Perinatal Overnutrition Exacerbates Adipose Tissue Inflammation Caused by High-Fat Feeding in C57BL/6J Mice. PLoS One. 2015; 10(3):e0121954. View in: PubMed

Leptin-dependent neuronal NO signaling in the preoptic hypothalamus facilitates reproduction. J Clin Invest. 2014 Jun 2; 124(6):2550-9. View in: PubMed

Hypothalamic Tanycytes Are an ERK-Gated Conduit for Leptin into the Brain. Cell Metab. 2014 Feb 4; 19(2):293-301. View in: PubMed

Tanycyte-like cells form a blood-cerebrospinal fluid barrier in the circumventricular organs of the mouse brain. J Comp Neurol. 2013 Oct 15; 521(15):3389-405. View in: PubMed

The obesogenic effect of high fructose exposure during early development. Nat Rev Endocrinol. 2013 Aug; 9(8):494-500. View in: PubMed

Tanycytic VEGF-A boosts blood-hypothalamus barrier plasticity and access of metabolic signals to the arcuate nucleus in response to fasting. Cell Metab. 2013 Apr 2; 17(4):607-17. View in: PubMed

Organizational actions of metabolic hormones. Front Neuroendocrinol. 2013 Jan; 34(1):18-26. View in: PubMed

Development of the hypothalamic melanocortin system. Front Endocrinol (Lausanne). 2013; 4:38. View in: PubMed

Nutritional programming of hypothalamic development: critical periods and windows of opportunity. Int J Obes Suppl. 2012 Dec; 2(Suppl 2):S19-24. View in: PubMed

RIPping off GABA release in hypothalamic circuits causes obesity. Cell Metab. 2012 Nov 7; 16(5):557-8. View in: PubMed

Anxiety-like behaviour and associated neurochemical and endocrinological alterations in male pups exposed to prenatal stress. Psychoneuroendocrinology. 2012 Oct; 37(10):1646-58. View in: PubMed

Alteration in neonatal nutrition causes perturbations in hypothalamic neural circuits controlling reproductive function. J Neurosci. 2012 Aug 15; 32(33):11486-94. View in: PubMed

Embryonic birthdate of hypothalamic leptin-activated neurons in mice. Endocrinology. 2012 Aug; 153(8):3657-67. View in: PubMed

Weighing on autophagy: A novel mechanism for the CNS regulation of energy balance. Cell Cycle. 2012 Apr 15; 11(8):1477-8. View in: PubMed

Loss of Autophagy in Pro-opiomelanocortin Neurons Perturbs Axon Growth and Causes Metabolic Dysregulation. Cell Metab. 2012 Feb 8; 15(2):247-55. View in: PubMed

Distinct roles for specific leptin receptor signals in the development of hypothalamic feeding circuits. J Neurosci. 2012 Jan 25; 32(4):1244-52. View in: PubMed

Maternal diabetes compromises the organization of hypothalamic feeding circuits and impairs leptin sensitivity in offspring. Endocrinology. 2011 Nov; 152(11):4171-9. View in: PubMed

Developmental effects of ghrelin. Peptides. 2011 Nov; 32(11):2362-6. View in: PubMed

Astrocytes modulate distribution and neuronal signaling of leptin in the hypothalamus of obese A vy mice. J Mol Neurosci. 2011 Mar; 43(3):478-84. View in: PubMed

Neurodevelopmental actions of leptin. Brain Res. 2010 Sep 2; 1350:2-9. View in: PubMed

Large litter rearing enhances leptin sensitivity and protects selectively bred diet-induced obese rats from becoming obese. Endocrinology. 2010 Sep; 151(9):4270-9. View in: PubMed

Differential distribution of tight junction proteins suggests a role for tanycytes in blood-hypothalamus barrier regulation in the adult mouse brain. J Comp Neurol. 2010 Apr 1; 518(7):943-62. View in: PubMed

Role of early hormonal and nutritional experiences in shaping feeding behavior and hypothalamic development. J Nutr. 2010 Mar; 140(3):653-7. View in: PubMed

Distribution of leptin-sensitive cells in the postnatal and adult mouse brain. J Comp Neurol. 2010 Feb 15; 518(4):459-76. View in: PubMed

Leptin, nutrition, and the programming of hypothalamic feeding circuits. Nestle Nutr Workshop Ser Pediatr Program. 2010; 65:25-35; discussion 35-9. View in: PubMed

Development of hypothalamic neural networks controlling appetite. Forum Nutr. 2010; 63:84-93. View in: PubMed

Early life origins of obesity: role of hypothalamic programming. J Pediatr Gastroenterol Nutr. 2009 Mar; 48 Suppl 1:S31-8. View in: PubMed

Three weeks of postweaning exercise in DIO rats produces prolonged increases in central leptin sensitivity and signaling. Am J Physiol Regul Integr Comp Physiol. 2009 Mar; 296(3):R537-48. View in: PubMed

Crossing the border: developmental regulation of leptin transport to the brain. Endocrinology. 2008 Mar; 149(3):875-6. View in: PubMed

Hypothalamic neural projections are permanently disrupted in diet-induced obese rats. Cell Metab. 2008 Feb; 7(2):179-85. View in: PubMed

Development of leptin-sensitive circuits. J Neuroendocrinol. 2007 Aug; 19(8):575-82. View in: PubMed

Neuronal-glial-endothelial interactions and cell plasticity in the postnatal hypothalamus: implications for the neuroendocrine control of reproduction. Psychoneuroendocrinology. 2007 Aug; 32 Suppl 1:S46-51. View in: PubMed

Developmental programming of hypothalamic feeding circuits. Clin Genet. 2006 Oct; 70(4):295-301. View in: PubMed

Cord blood leptin and IGF-I in relation to birth weight differences and head circumference in monozygotic twins. J Pediatr Endocrinol Metab. 2006 Jan; 19(1):3-9. View in: PubMed

Minireview: Leptin and development of hypothalamic feeding circuits. Endocrinology. 2004 Jun; 145(6):2621-6. View in: PubMed

Trophic action of leptin on hypothalamic neurons that regulate feeding. Science. 2004 Apr 2; 304(5667):108-10. View in: PubMed

Transforming growth factor beta1 may directly influence gonadotropin-releasing hormone gene expression in the rat hypothalamus. Endocrinology. 2004 Apr; 145(4):1794-801. View in: PubMed

Formation of projection pathways from the arcuate nucleus of the hypothalamus to hypothalamic regions implicated in the neural control of feeding behavior in mice. J Neurosci. 2004 Mar 17; 24(11):2797-805. View in: PubMed

Galanin modulates the activity of proopiomelanocortin neurons in the isolated mediobasal hypothalamus of the male rat. Neuroscience. 2002; 112(2):475-85. View in: PubMed

Evidence that TGF beta may directly modulate POMC mRNA expression in the female rat arcuate nucleus. Endocrinology. 2001 Sep; 142(9):4055-65. View in: PubMed

Evidence that TGFß May Directly Modulate POMC mRNA Expression in the Female Rat Arcuate Nucleus. Endocrinology. 2001 Sep 01; 142(9):4055-4065. View in: PubMed

Microwave strategy for improving the simultaneous detection of estrogen receptor and galanin receptor mRNA in the rat hypothalamus. J Histochem Cytochem. 2001 Jul; 49(7):901-10. View in: PubMed

Comparative distribution of mRNA encoding the growth hormone secretagogue-receptor (GHS-R) in Microcebus murinus (Primate, lemurian) and rat forebrain and pituitary. J Comp Neurol. 2001 Jan 15; 429(3):469-89. View in: PubMed

Median eminence nitric oxide signaling. Brain Res Brain Res Rev. 2000 Nov; 34(1-2):27-41. View in: PubMed

Mu opioid receptor mRNA expression in neuronal nitric oxide synthase-immunopositive preoptic area neurons. Brain Res Mol Brain Res. 2000 Aug 14; 80(1):46-52. View in: PubMed

Evidence that members of the TGFbeta superfamily play a role in regulation of the GnRH neuroendocrine axis: expression of a type I serine-threonine kinase receptor for TGRbeta and activin in GnRH neurones and hypothalamic areas of the female rat. J Neuroendocrinol. 2000 Jul; 12(7):665-70. View in: PubMed

Growth-associated protein-43 messenger ribonucleic acid expression in gonadotropin-releasing hormone neurons during the rat estrous cycle. Endocrinology. 2000 May; 141(5):1648-57. View in: PubMed

Expression of GalR1 and GalR2 galanin receptor messenger ribonucleic acid in proopiomelanocortin neurons of the rat arcuate nucleus: effect of testosterone. Endocrinology. 2000 May; 141(5):1780-94. View in: PubMed

Evidence for expression of galanin receptor Gal-R1 mRNA in certain gonadotropin releasing hormone neurones of the rostral preoptic area. J Neuroendocrinol. 1999 Oct; 11(10):805-12. View in: PubMed

Mu-opioid receptor mRNA expression in proopiomelanocortin neurons of the rat arcuate nucleus. Brain Res Mol Brain Res. 1999 Jun 18; 70(1):155-8. View in: PubMed

Expression of the galanin receptor subtype Gal-R2 mRNA in the rat hypothalamus. J Chem Neuroanat. 1999 Jun; 16(4):265-77. View in: PubMed

Definitive evidence for the existence of morphological plasticity in the external zone of the median eminence during the rat estrous cycle: implication of neuro-glio-endothelial interactions in gonadotropin-releasing hormone release. Neuroscience. 1999; 94(3):809-19. View in: PubMed

Effects of estrous cyclicity on the expression of the galanin receptor Gal-R1 in the rat preoptic area: a comparison with the male. Endocrinology. 1998 Oct; 139(10):4127-39. View in: PubMed

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