RT Journal Article T1 Exposure to a Highly Caloric Palatable Diet During Pregestational and Gestational Periods Affects Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Adiposity and Anxiety-Like Behaviors in Male Rat Offspring A1 Ramírez López, María Teresa A1 Vázquez, Mariam A1 Bindila, Laura A1 Lomazzo, Ermelinda A1 Hofmann, Clementine A1 Blanco, Rosario Noemí A1 Alén Fariñas, Francisco A1 Antón, María A1 Decara, Juan A1 Ouro, Daniel A1 Orio Ortiz, Laura A1 Suarez, Juan A1 Lutz, Beat A1 Rodríguez De Fonseca, Fernando Antonio A1 Gómez De Heras, María Raquel AB Exposure to unbalanced diets during pre-gestational and gestational periods may result in long-term alterations in metabolism and behavior. The contribution of the endocannabinoid system to these long-term adaptive responses is unknown. In the present study, we investigated the impact of female rat exposure to a hypercaloric-hypoproteic palatable diet during pre-gestational, gestational and lactational periods on the development of male offspring. In addition, the hypothalamic and hippocampal endocannabinoid contents at birth and the behavioral performance in adulthood were investigated. Exposure to a palatable diet resulted in low weight offspring who exhibited low hypothalamic contents of arachidonic acid and the two major endocannabinoids (anandamide and 2-arachidonoylglycerol) at birth. Palmitoylethanolamide, but not oleoylethanolamide, also decreased. Additionally, pups from palatable diet-fed dams displayed lower levels of anandamide and palmitoylethanolamide in the hippocampus. The low-weight male offspring, born from palatable diet exposed mothers, gained less weight during lactation and although they recovered weight during the post-weaning period, they developed abdominal adiposity in adulthood. These animals exhibited anxiety-like behavior in the elevated plus-maze and open field test and a low preference for a chocolate diet in a food preference test, indicating that maternal exposure to a hypercaloric diet induces long-term behavioral alterations in male offspring. These results suggest that maternal diet alterations in the function of the endogenous cannabinoid system can mediate the observed phenotype of the offspring, since both hypothalamic and hippocampal endocannabinoids regulate feeding, metabolic adaptions to caloric diets, learning, memory, and emotions. PB Frontiers Media SA SN 1662-5153 YR 2016 FD 2016-01-06 LK https://hdl.handle.net/20.500.14352/121857 UL https://hdl.handle.net/20.500.14352/121857 LA eng NO Ramírez-López MT, Vázquez M, Bindila L, Lomazzo E, Hofmann C, Blanco RN, et al. Exposure to a Highly Caloric Palatable Diet During Pregestational and Gestational Periods Affects Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Adiposity and Anxiety-Like Behaviors in Male Rat Offspring. Frontiers in Behavioral Neuroscience. 2015;9. NO Este trabajo fue financiado por el Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (PI13/0226 para FR, CP12/03109 para JS y PSI-2012-35388 para RG), Red de Trastornos Adictivos (RD12/0028/0001 para FR), CIBERobn, Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, UE/FEDER (PI45403, CTS-8221, CTS-433 para FR), Consejería de Salud, Junta de Andalucía (PI0232/2008, PI0029/2008 y SAS111224 para JS y FR), y la Fundación Alemana para la Investigación (DFG, FOR926, proyecto CP1 para BL). MT RL ha sido financiado mediante una beca predoctoral FPU del Ministerio de Educación, Cultura y Deporte de España (AP-2009-0225); JS tiene un contrato de investigación “Miguel Servet” del Sistema Nacional de Salud, ISCIII (número de subvención CP14/00173). Los autores también agradecen a Claudia Schwitter por su ayuda y apoyo durante la extracción lipídica y el análisis BCA. DS Docta Complutense RD 27 jun 2025