Sebastien G. Bouret
Lille Neuroscience & Cognition
Development and Plasticity of the Neuroendocrine Brain
Inserm, University of Lille, CHU Lille
Agnès Nadjar (Magendie) and Xavier Fioramonti (NutriNeuro)
The not-so-sweet effect of maternal nutrition on metabolic programming and brain development
The growing prevalence of obesity and associated diseases such as type II diabetes is an important health concern, including among children and pregnant women. Epidemiological and pre-clinical studies suggested that alterations of the metabolic and hormonal environments during critical periods of development are associated with increased risks for obesity and type 2 diabetes in later life. There is general recognition that the developing brain is more susceptible to environmental insults than the adult brain. In particular, there is growing appreciation that developmental programming of hypothalamic neuroendocrine systems by the perinatal environment represents a possible cause for these diseases. This lecture will summarize the major stages of hypothalamic development and discuss potential periods of vulnerability for the development of hypothalamic neurons involved in energy balance and glucose regulation. It will also provide an overview of evidence concerning the action of hormones (including leptin and ghrelin) in programming the development and organization of hypothalamic melanocortin circuits. Recent data on the impact of maternal nutrition and low-calorie sweeteners consumption in the development and organization of hypothalamic circuits that regulate feeding and glucose homeostasis will also be presented.
Bouret SG, Draper SJ, & Simerly RB. Trophic action of leptin on hypothalamic neurons that regulate feeding. Science, 304(5667):108-110, 2004 (News & Views, p. 63-64; Science Editor’s Choice; also Nature Medicine, 12(1):52-53, 2006; and NIH 2004 Strategic Plan for NIH Obesity Research)
Bouret SG, Gorski JN, Kirigiti MA, Levin BE, & Simerly RB. Hypothalamic neural projections are permanently disrupted in diet-induced obese rats. Cell Metabolism, 7(2):179-185, 2008 (cover illustration; also 2009 Dana Alliance’s top findings in brain research)
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)
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 (also Cell Cycle (Perspective), 2012, 11(8): 1477-1478).
Steculorum SM, Collden G, Coupe B, Croizier S, Lockie S, Andrews Z, Jarosch F, Klussmann S, & Bouret SG. Ghrelin programs development of hypothalamic feeding circuits. The Journal of Clinical Investigation, 125(2), 846-858, 2015 (also J Clin Invest (commentary), 490-492, 2015).
Collden G, Balland E, Parkash J, Caron E, Langlet F, Prevot V, & Bouret SG. Neonatal overnutrition causes early alterations in the central response to peripheral ghrelin. Molecular Metabolism, 4(1):15-24, 2015.
Croizier SM, Prevot V, Bouret SG. Leptin controls parasympathetic wiring of the pancreas during embryonic life. Cell Reports, 15(1):36-44, 2016
van der Klaauw A, Croizier S, Mendes de Oliveira E, Banton M, Stadler L, Kong Y, Hendricks A, Tandon P, Keogh J, Park S, Papadia S, Henning E, Bounds R, Bochukova E, Mistry V, O’Rahilly S, Simerly RB, INTERVAL, UK10K consortium, Minchin JEN, Barroso I, Jones Y, Bouret SG*, Farooqi IS*. * co-senior/corresponding authors. Semaphorin 3 signaling directs the development of hypothalamic melanocortin circuits involved in mammalian energy homeostasis. Cell, 176(4):729-742, 2019 (also Nat Rev Endocrinol (research highlight), 15:191, 2019 and Trends Neurosci (spotlight), 42(7):439-440, 2019)
Park S, Aintablian A, Coupe B, Bouret SG. The endoplasmic reticulum stress-autophagy pathway controls hypothalamic development and energy balance regulation in leptin-deficient neonates. Nature Communications, 11:1914, 2020
Park S, Jang A*, Bouret SG. Maternal obesity-induced endoplasmic reticulum stress causes metabolic alterations and abnormal hypothalamic development in the offspring. PLoS Biol, 18(3): e3000296, 2020 (also Nat Rev Endocrinol (research highlight), 2020)
Coupe B, Leloup C, Asiedu K, Maillard J, Penicaud L, Horvath TL, Bouret SG. Defective autophagy in Sf1 neurons perturbs the metabolic response to fasting and causes mitochondrial dysfunction, Molecular Metabolism, 47:101186, 2021