Jörgensen Sara K M, Surridge-Smith May, Jones Kimberley, Maletínská Lenka, Allen Nicholas D, Petrik David
School of Biosciences, Cardiff University, Cardiff, Wales, United Kingdom.
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic.
PLoS One. 2025 Aug 13;20(8):e0329268. doi: 10.1371/journal.pone.0329268. eCollection 2025.
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.
抗肥胖药物（AOMs）已成为人类医学中处方量最大的药物之一。虽然已知AOMs会影响下丘脑的成年神经发生，但其对下丘脑神经元功能成熟的影响仍未得到探索。鉴于AOMs作用于内侧基底下丘脑（MBH）中的神经元，而这些神经元在调节能量平衡中起关键作用，我们推测AOMs可能会影响这些神经元的功能成熟，从而可能重塑MBH。为了对此进行研究，我们将源自人类诱导多能干细胞（hiPSCs）的下丘脑神经元暴露于两种抗肥胖化合物司美格鲁肽和脂质化催乳素释放肽（LiPR）中。与我们的预期相反，在神经元成熟过程中用司美格鲁肽或LiPR处理并未影响表达厌食性促阿片黑素细胞皮质素（POMC+）的神经元比例。此外，LiPR并未改变POMC+神经元的形态或对厌食性神经元的代谢或发育至关重要的选定基因的表达。此外，LiPR并未影响小鼠MBH中成年生成的POMC+神经元的比例。综上所述，这些结果表明AOMs不会影响厌食性下丘脑神经元的功能成熟。
