Anti-obesity medications (AOMs) have become one of the most prescribed drugs in human medicine. While AOMs are known to impact adult neurogenesis in the hypothalamus, their effects on the functional maturation of hypothalamic neurons remain unexplored. Given that AOMs target neurons in the Medial Basal Hypothalamus (MBH), which play a crucial role in regulating energy homeostasis, we hypothesized that AOMs might influence the functional maturation of these neurons, potentially rewiring the MBH. To investigate this, we exposed hypothalamic neurons derived from human induced pluripotent stem cells (hiPSCs) to Semaglutide and lipidized prolactin-releasing peptide (LiPR), two anti-obesity compounds. Contrary to our expectations, treatment with Semaglutide or LiPR during neuronal maturation did not affect the proportion of anorexigenic, Pro-opiomelanocortin-expressing (POMC+) neurons. Additionally, LiPR did not alter the morphology of POMC+ neurons or the expression of selected genes critical for the metabolism or development of anorexigenic neurons. Furthermore, LiPR did not impact the proportion of adult-generated POMC+ neurons in the mouse MBH. Taken together, these results suggest that AOMs do not influence the functional maturation of anorexigenic hypothalamic neurons.

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Prague Czech Republic

School of Biosciences Cardiff University Cardiff Wales United Kingdom

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