The overweight and obesity pandemics and associated diseases such as type 2 diabetes, are major public health concerns. In the lab, we aim to decipher the role of the interplay between environmental changes and genetics in the onset of these pathologies. As commonly thought, obesity is not simply defined as carrying too much fat, but results from complex interactions between lifestyle factors, including daily stress and regulation of gene expression. Stress and feeding are closely intertwined, and show gender specificities with women being at higher risk to develop binge-eating behavior, and consequently obesity. While sex differences in gene expression has been described, their role in shaping sex differences in obesity etiology has not been fully explored. By employing cutting-edge techniques including transcriptomics, in vivo calcium (Ca²⁺) fiber photometry, optogenetics, electrophysiology, and super-resolution microscopy, in parallel with neurodevelopmental, histological, and behavioral approaches, our goal is to contribute to the genetic and anatomic characterization of novel sexually dimorphic brain feeding-circuits.

Several brain areas are known to control energy metabolism, and accumulating evidence converges towards a central role of the hypothalamus. A particularly important metabolic function has been given to the hypothalamic arcuate nucleus (ARH) which contains two functionally antagonistic neuronal populations, the pro-opiomelanocortin (POMC)- and the agouti-related peptide/neuropeptide Y (AgRP/NPY)-expressing neurons that suppress and stimulate feeding, respectively. These neurons, often seen as first-order neurons which maintain energy balance through downstream hypothalamic and extra-hypothalamic targets, are actually integrated in more complex neuronal networks. Indeed, they receive central information through GABAergic (inhibitory) and glutamatergic (excitatory) inputs coming from a plethora of brain areas including telencephalic, and hypothalamic structures. However, how these synaptic contacts develop, and how they control POMC- and AgRP-related functions has not been thoroughly explored.

Our goal is to better delineate and characterize POMC- and AgRP-dependent feeding circuits, and to assess how environmental factors directly impinge on their development, and function potentially leading to the onset of metabolic disorders.

Keywords

• obesity
• maternal obesity
• stress
• hypothalamus
• feeding
• wiring
• synaptic plasticity