Bouret Lab

RESEARCH TOPICS

Cellular and hormonal mechanisms underlying hypothalamic development
Early life determinants of obesity and diabetes

RESEARCH OVERVIEW

Neuron proliferation in the embryonic hypothalamus. Confocal image showing newly generated cells (BrdU-positive, green fluorescence) in the embryonic hypothalamus. Nuclei are depicted in blue, nestin-positive cell progenitors are red.
The incidence of childhood obesity is increasing at an alarming rate and this worldwide epidemic represents an ominous predictor of increases in diseases such as type 2 diabetes and metabolic syndrome. Epidemiological and animals studies suggest that maternal obesity and alterations in postnatal nutrition are associated with increased risks for obesity, hypertension, and type 2 diabetes in the offspring. Furthermore, there is also growing appreciation that developmental programming of neuroendocrine systems by the perinatal environment represents a possible cause for these diseases.

Currently, we are exploring the role of perinatal hormones in influencing the development of hypothalamic pathways involved in appetite regulation. We are also examining the cellular and molecular mechanisms underlying hypothalamic development.

KEY FINDINGS

The loss of autophagy in POMC neurons causes metabolic defects and causes abnormal maturation of hypothalamic axonal projections (Coupe et al., Cell Metabolism, 2012)
Offspring of diabetic mothers display marked differences in the organization of appetite-regulating hypothalamic neural circuits (Steculorum et al., Endocrinology, 2011)

CURRENT FUNDING

RO1 National Institute of Health (NIDDK), Hormonal and nutritional regulation of hypothalamic neurogenesis. $1,057,000 TDC

PUBLICATIONS

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, in press, 2012
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, in press, 2012
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)
Caron E, Sachot C, Prevot V, Bouret SG. Distribution of leptin-sensitive cells in the postnatal and adult mouse brain. Journal of Comparative Neurology, 518(4):459-476, 2010
Patterson C, Bouret SG, Park S, Dunn-Meynell, Levin BE. Large litter rearing enhances leptin sensitivity and protects selectively bred diet-induced obese rats from becoming obese. Endocrinology, 151(9), 4270-4279, 2010
Bouret SG, Gorski JN, Kirigiti MA, Levin BE, Simerly RB. Neural Projections from the arcuate nucleus of the hypothalamus are permanently disrupted in diet-induced obese rats. Cell Metabolism, 7(2):179-185, 2008 (cover article)
Bouret SG, Draper SJ, Simerly RB. Trophic action of leptin on hypothalamic neurons that regulate feeding. Science, 304(5667):108-110, 2004.
Bouret SG, Draper SJ, Simerly RB. Formation of projection pathways from the arcuate nucleus of the hypothalamus to hypothalamic regions implicated in the neural control of feeding behavior in mice. Journal of Neuroscience, 24(11):2797-2805, 2004.