RT Journal Article T1 A moderate diet restriction during pregnancy alters the levels of endocannabinoids and endocannabinoid-related lipids in the hypothalamus, hippocampus and olfactory bulb of rat offspring in a sex-specific manner A1 Ramírez López, María Teresa A1 Vázquez, Mariam A1 Lomazzo, Ermelinda A1 Hofmann, Clementine A1 Blanco Velilla, Rosario Noemí A1 Alén Fariñas, Francisco A1 Antón, María A1 Decara, Juan A1 Arco, Rocío A1 Orio Ortiz, Laura A1 Suárez, Juan A1 Lutz, Beat A1 Gómez De Heras, María Raquel A1 Bindila, Laura A1 Rodríguez De Fonseca, Fernando Antonio AB Undernutrition during pregnancy has been associated to increased vulnerability to develop metabolic and behavior alterations later in life. The endocannabinoid system might play an important role in these processes. Therefore, we investigated the effects of a moderate maternal calorie-restricted diet on the levels of the endocannabinoid 2-arachidonoyl glycerol (2-AG), arachidonic acid (AA) and the N-acylethanolamines (NAEs) anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) in the brain of newborn rat offspring. We focused on brain structures involved in metabolism, feeding behavior, as well as emotional and cognitive responses. Female Wistar rats were assigned during the entire pregnancy to either control diet (C) or restriction diet (R), consisting of a 20% calorie-restricted diet. Weight gain and caloric intake of rat dams were monitored and birth outcomes were assessed. 2-AG, AA and NAE levels were measured in hypothalamus, hippocampus and olfactory bulb of the offspring. R dams displayed lower gain weight from the middle pregnancy and consumed less calories during the entire pregnancy. Offspring from R dams were underweight at birth, but litter size was unaffected. In hypothalamus, R male offspring displayed decreased levels of AA and OEA, with no change in the levels of the endocannabinoids 2-AG and AEA. R female exhibited decreased 2-AG and PEA levels. The opposite was found in the hippocampus, where R male displayed increased 2-AG and AA levels, and R female exhibited elevated levels of AEA, AA and PEA. In the olfactory bulb, only R female presented decreased levels of AEA, AA and PEA. Therefore, a moderate diet restriction during the entire pregnancy alters differentially the endocannabinoids and/or endocannabinoid-related lipids in hypothalamus and hippocampus of the underweight offspring, similarly in both sexes, whereas sex-specific alterations occur in the olfactory bulb. Consequently, endocannabinoid and endocannabinoid-related lipid signaling alterations might be involved in the long-term and sexual dimorphism effects commonly observed after undernutrition and low birth weight. PB PLOS ONE YR 2017 FD 2017-03-27 LK https://hdl.handle.net/20.500.14352/116625 UL https://hdl.handle.net/20.500.14352/116625 LA eng NO Ramírez-López MT, Vázquez M, Lomazzo E, Hofmann C, Blanco RN, Alén F, Antón M, Decara J, Arco R, Orio L, Suárez J, Lutz B, Gómez de Heras R, Bindila L, Rodríguez de Fonseca F. A moderate diet restriction during pregnancy alters the levels of endocannabinoids and endocannabinoid-related lipids in the hypothalamus, hippocampus and olfactory bulb of rat offspring in a sex-specific manner. PLoS One. 2017 Mar 27;12(3):e0174307. doi: 10.1371/journal.pone.0174307. PMID: 28346523; PMCID: PMC5367805. NO Una restricción moderada de la dieta durante todo el embarazo altera diferencialmente los endocannabinoides y/o los lípidos relacionados con los endocannabinoides en el hipotálamo y el hipocampo de la descendencia con bajo peso, de manera similar en ambos sexos, mientras que las alteraciones específicas del sexo ocurren en el bulbo olfatorio. En consecuencia, las alteraciones de la señalización de los lípidos relacionados con los endocannabinoides y los endocannabinoides podrían estar involucrados en los efectos del dimorfismo sexual a largo plazo que se observan comúnmente después de la desnutrición y el bajo peso al nacer. NO Ministerio de Economía y Competitividad (PI12/02261, PI16/11698, PI16/01374, PSI2012-35388 y CP12/03109) NO Red de Trastornos Adictivos UE/ERDF (RD12/0028/0001) NO CIBERobn NO Consejería de Economía, Innovación y Ciencia, Junta de Andalucía NO UE/ERDF (PI45403, CTS-8221, CTS-433 ) NO Consejería de Salud, Junta de Andalucía (SAS111224) NO German Research Foundation DFG (FOR926, project CP1 ; CRC1080, subproject B08) NO Beca FPU del Ministerio de Educación y Ciencia DS Docta Complutense RD 18 abr 2025