Dr. Sebastien Bouret at Children’s Hospital Los Angeles is interested in how levels of hormones that regulate appetite impact brain function. Specifically, his group is exploring how levels of these hormones early in life influence brain development and ultimately impact appetite regulation and metabolic health in adulthood.
His lab works on this question as it relates to typically developing individuals, and, with FPWR support, in individual with PWS. He’s been using mouse models to understand how the high levels of ghrelin that are characteristic of PWS affect brain development and neuronal cell function in the hypothalamus, the part of the brain that is key in controlling appetite.
This finding is particularly important in light of another recent study by Dr. Driscoll’s group and earlier studies by Dr. Tauber and colleagues, all showing that infants and young children with PWS have abnormally high levels of ghrelin very early in life, well before the onset of obesity.
With continued funding from FPWR, (Development of appetite-related neural circuits in a mouse model for PWS , year 2) Dr. Bouret is currently examining treatments that may help rescue the impaired neuronal function caused by exposure to high ghrelin levels. An additional summary of the article can be found here.
In work recently published in the highly regarded Journal of Clinical Investigation, Dr. Bouret’s group shows that abnormal levels of circulating ghrelin during the newborn period negatively impacts hypothalamic brain development, setting the groundwork that leads to abnormal appetite regulation and obesity in adulthood. [Neonatal ghrelin programs development of hypothalamic feeding circuits].
