Philipp Hammerschmidt, Sophie M Steculorum, Cécile L Bandet, Almudena Del Río-Martín, Lukas Steuernagel, Vivien Kohlhaas, Marvin Feldmann, Luis Varela, Adam Majcher, Marta Quatorze Correia, Rhena F U Klar, Corinna A Bauder, Ecem Kaya, Marta Porniece, Nasim Biglari, Anna Sieben, Tamas L Horvath, Thorsten Hornemann, Susanne Brodesser, Jens C Brüning
Dysregulation of hypothalamic ceramides has been associated with disrupted neuronal pathways in control of energy and glucose homeostasis. However, the specific ceramide species promoting neuronal lipotoxicity in obesity have remained obscure. Here, we find increased expression of the C16:0 ceramide-producing ceramide synthase (CerS)6 in cultured hypothalamic neurons exposed to palmitate in vitro and in the hypothalamus of obese mice. Conditional deletion of CerS6 in hypothalamic neurons attenuates high-fat diet (HFD)-dependent weight gain and improves glucose metabolism...
November 29, 2023: Nature Communications