Ramírez-López, María TeresaVázquez, MariamLomazzo, ErmelindaHofmann, ClementineBlanco, Rosario NoemiAlén, FranciscoAntón, MaríaDecara, JuanArco, RocíoOrio, LauraSuárez, JuanLutz, BeatGómez de Heras, RaquelBindila, LauraRodríguez de Fonseca, Fernando2017-05-302017-05-302017-03-27Ramírez-López MT,Vázquez M, Lomazzo E, Hofmann C, Blanco RN, Alén F, et al. 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;12(3):e0174307.http://hdl.handle.net/10668/2687Existe para su consulta material suplementario aportado por el editor.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.enAn error occurred on the license name.An error occurred getting the license - uri.DesnutriciónEmbarazoEndocannabinoidesÁcido AraquidónicoEncéfaloAnimales recién nacidosRatas wistarFemeninoMasculinoEmocionesCogniciónRestricción calóricaHipotálamoHipocampoBulbo olfatorioPeso al nacerMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::MalnutritionMedical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::PregnancyMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::EndocannabinoidsMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Arachidonic AcidsMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::BrainMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, NewbornMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, WistarMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::EmotionsMedical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::CognitionMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet::Energy Intake::Caloric RestrictionMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::HypothalamusMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::HippocampusMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Olfactory Pathways::Olfactory BulbMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Anthropometry::Body Weights and Measures::Body Size::Body Weight::Birth Weightresearch article28346523open access10.1371/journal.pone.01743071932-6203PMC5367805