Principal Investigator, MPI for Metabolism Research
The general interest of the Steculorum Lab is to decipher the exact neuronal networks that govern fundamental behavioral and physiological processes such as feeding or maintenance of steady body weight and glycemia. Dr. Steculorum and her research group notably aim to uncover the developmental wiring of neurocircuits controlling energy and glucose homeostasis as well as their precise functions with the intent of furthering our understanding of the pathophysiology of obesity and Type 2 Diabetes Mellitus.
Our research: Despite the fact that metabolic disorders are indisputably associated with aging, they are increasingly diagnosed in childhood and have recognized roots in very early life. Indeed, compelling evidence from animals and epidemiological studies reveal that abnormal changes in the maternal, fetal, and neonatal environment substantially contribute to the onset of these metabolic diseases. Notably, changes in the nutritional and/or hormonal environment during gestation and/or lactation (e.g. maternal obesity/malnutrition or diabetes) can permanently alter the development of “brain-metabolic” pathways, which directly impinges on their life-long functions and predisposes individuals to develop metabolic diseases later in life.
In this context, our team is pursuing two main lines of research. On the one hand, we aim at defining the architecture and the functional principles of neuronal-based circuits controlling energy and glucose homeostasis in adults. By doing so, we hope to better understand how the brain controls metabolic processes and to identify the exact neurocircuits involved in these events. On the other hand, we also focus on uncovering new mechanisms underlying the developmental programming of metabolic neuronal networks. Altogether, we intend to pinpoint novel brain-metabolic pathways sensitive to abnormal perinatal milieus that could ultimately contribute to the onset of metabolic dysfunctions.
Our successes: We are implementing various approaches to decipher novel neurocircuits controlling feeding behavior in mice and novel mechanisms underlying the perinatal neuro-programming of metabolic diseases. Our current projects are notably based on previous discoveries of Dr. Steculorum demonstrating a key role for metabolic hormones such as ghrelin in the ontogeny of brain-metabolic pathways, as well as on recent findings highlighting novel neuronal players and networks controlling energy and glucose homeostasis.
Our goals: Our group is keen to deepen our understanding of the fundamental principles of the central control of metabolism from embryo to adult, and aim to answer central questions such as: How does the organism sense and integrate its environment to adapt its behavior according to its physiological and nutritional needs?Which are the precise mechanisms and factors triggering abnormal brain wiring and consequent metabolic programming? Could we bypass the unfortunate “metabolic destiny” of an individual?
Our methods/techniques: We are using genetic mouse models and modern technologies in systems neuroscience such as optogenetics, chemogenetics, and in vivo calcium imaging, in concert with a broad range of tests assessing metabolism (i.e. in vivo physiology), behavior, and development of neurocircuit.
Figure: Fluorescent microphotograph showing orexigenic neurons expressing the neuropeptide-Y in the arcuate nucleus of the hypothalamus of a mouse expressing the green fluorescent protein under the transcriptional control of the Npy-promoter.