RT Journal Article T1 Maternal Caloric Restriction Implemented during the Preconceptional and Pregnancy Period Alters Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Overweight and Increased Adiposity at Adulthood in Male Rat Offspring A1 Ramírez López, María Teresa A1 Vázquez, Mariam A1 Bindila, Laura A1 Lomazzo, Ermelinda A1 Hofmann, Clementine A1 Blanco, Rosarío Noemí A1 Alén Fariñas, Francisco A1 Antón, María A1 Decara, Juan A1 Arco, Rocío A1 Ouro, Daniel A1 Orio Ortiz, Laura A1 Suárez, Juan A1 Lutz, Beat A1 Gómez De Heras, María Raquel A1 Rodríguez De Fonseca, Fernando Antonio AB Exposure to inadequate nutritional conditions in critical windows of development has been associated to disturbances on metabolism and behavior in the offspring later in life. The role of the endocannabinoid system, a known regulator of energy expenditure and adaptive behaviors, in the modulation of these processes is unknown. In the present study, we investigated the impact of exposing rat dams to diet restriction (20% less calories than standard diet) during pre-gestational and gestational periods on: (a) neonatal outcomes; (b) endocannabinoid content in hypothalamus, hippocampus and olfactory bulb at birth; (c) metabolism-related parameters; and (d) behavior in adult male offspring. We found that calorie-restricted dams tended to have a reduced litter size, although the offspring showed normal weight at birth. Pups from calorie-restricted dams also exhibited a strong decrease in the levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), arachidonic acid (AA) and palmitoylethanolamide (PEA) in the hypothalamus at birth. Additionally, pups from diet-restricted dams displayed reduced levels of AEA in the hippocampus without significant differences in the olfactory bulb. Moreover, offspring exhibited increased weight gain, body weight and adiposity in adulthood as well as increased anxiety-related responses. We propose that endocannabinoid signaling is altered by a maternal caloric restriction implemented during the preconceptional and pregnancy periods, which might lead to modifications of the hypothalamic and hippocampal circuits, potentially contributing to the long-term effects found in the adult offspring. PB Frontiers Media SA SN 1662-5153 YR 2016 FD 2016-11-01 LK https://hdl.handle.net/20.500.14352/121790 UL https://hdl.handle.net/20.500.14352/121790 LA eng NO Ramírez-López MT, Vázquez M, Bindila L, Lomazzo E, Hofmann C, Blanco RN, et al. Maternal caloric restriction implemented during the preconceptional and pregnancy period alters hypothalamic and hippocampal endocannabinoid levels at birth and induces overweight and increased adiposity at adulthood in male rat offspring. Frontiers in Behavioral Neuroscience. 2016;10(NOV). NO Este trabajo fue financiado por el Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (PI13/0226 a FRF, CP12/03109 a JS y PSI-2012-35388 a RGH), la Red de Trastornos Adictivos (RD12/0028/0001 a FRF), CIBERobn, la Consejería de Economía, Innovación y Ciencia de la Junta de Andalucía, UE/FEDER (PI45403, CTS-8221, CTS-433 a FRF), la Consejería de Salud de la Junta de Andalucía (SAS111224 a JS y FRF), y la Fundación Alemana para la Investigación Científica DFG (FOR926, proyecto CP1 a BL). MTR-L ha sido financiada mediante una beca predoctoral FPU del Ministerio de Educación, Cultura y Deporte (AP-2009-0225); JS tiene un contrato de investigación “Miguel Servet” del Sistema Nacional de Salud, ISCIII (número de subvención CP12/03109). Los autores también agradecen a Claudia Schwitter por su ayuda y apoyo durante la extracción lipídica y el análisis BCA. DS Docta Complutense RD 26 jun 2025