RT Journal Article T1 Maternal hypercaloric diet affects factors involved in lipid metabolism and the endogenous cannabinoid systems in the hypothalamus of adult offspring: sex-specific response of astrocytes to palmitic acid and anandamide A1 Rivera, Patricia A1 Guerra Cantera, Santiago A1 Vargas, Antonio A1 Díaz, Francisca A1 García Úbeda, Rocío A1 Tovar, Rubén A1 Ramírez López, María Teresa A1 Argente, Jesús A1 Rodríguez De Fonseca, Fernando Antonio A1 Suárez, Juan A1 Chowen, Julie A AB Aim: We aimed to investigate whether maternal malnutrition during gestation/lactation induces long-lasting changes on inflammation, lipid metabolism and endocannabinoid signaling in the adult offspring hypothalamus and the role of hypothalamic astrocytes in these changes.Methods: We analyzed the effects of a free-choice hypercaloric palatable diet (P) during (pre)gestation, lactation and/or post-weaning on inflammation, lipid metabolism and endogenous cannabinoid signaling in the adult offspring hypothalamus. We also evaluated the response of primary hypothalamic astrocytes to palmitic acid and anandamide.Results: Postnatal exposure to a P diet induced factors involved in hypothalamic inflammation (Tnfa and Il6) and gliosis (Gfap, vimentin and Iba1) in adult offspring, being more significant in females. In contrast, maternal P diet reduced factors involved in astrogliosis (vimentin), fatty acid oxidation (Cpt1a) and monounsaturated fatty acid synthesis (Scd1). These changes were accompanied by an increase in the expression of the genes for the cannabinoid receptor (Cnr1) and Nape-pld, an enzyme involved in endocannabinoid synthesis, in females and a decrease in the endocannabinoid degradation enzyme Faah in males. These changes suggest that the maternal P diet results in sex-specific alterations in hypothalamic endocannabinoid signaling and lipid metabolism. This hypothesis was tested in hypothalamic astrocyte cultures, where palmitic acid (PA) and the polyunsaturated fatty acid N-arachidonoylethanolamine (anandamide or AEA) were found to induce similar changes in the endocannabinoid system (ECS) and lipid metabolism.Conclusion: These results stress the importance of both maternal diet and sex in long term metabolic programming and suggest a possible role of hypothalamic astrocytes in this process. PB Taylor & Francis SN 1028-415X YR 2022 FD 2022-05-25 LK https://hdl.handle.net/20.500.14352/116615 UL https://hdl.handle.net/20.500.14352/116615 LA eng NO Rivera P, Guerra-Cantera S, Vargas A, Díaz F, García-Úbeda R, Tovar R, Ramírez-López MT, Argente J, de Fonseca FR, Suárez J, Chowen JA. Maternal hypercaloric diet affects factors involved in lipid metabolism and the endogenous cannabinoid systems in the hypothalamus of adult offspring: sex-specific response of astrocytes to palmitic acid and anandamide. Nutr Neurosci. 2022 May;25(5):931-944. doi: 10.1080/1028415X.2020.1821519. Epub 2020 Sep 21. PMID: 32954972. NO La dieta materna impacta en la gliosis y en los factores inflamatorios en el hipotálamo así como en los componentes del sistema endocannabinoide en la descendencia, habiendo diferencias en función del sexo. Estos aspectos podrían estar implicados en la programación metabólica y conductual a largo plazo y sugieren un posible papel de los astrocitos hipotalámicos en este proceso. Este trabajo aporta información valiosa para el conocimiento de la patogenia de la obesidad y trastornos del neurodesarrollo. Permite estudiar mecanismos implicados en dicha patología. NO Instituto de Salud Carlos III: [Grant Number PI16/01374, PI16/00485, PI16/01698, CPII17/00024, CD19/00068, CP19/00068, PI16/01374, PI19/ 00343, PI19/00166) NO CIBEROBN and Ministerio de Economía y Competitividad: [Grant Number BFU2017-82565-C2-1-R]. DS Docta Complutense RD 12 abr 2025