title: 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.
abstract: 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.
authors.affiliation: Departamento de Psicobiología. Facultad de Psicología, Universidad Complutense de Madrid. Campus de Somosaguas s/n, Pozuelo de Alarcón, Madrid, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Ramírez-López
authors.affiliation: Departamento de Psicobiología. Facultad de Psicología, Universidad Complutense de Madrid. Campus de Somosaguas s/n, Pozuelo de Alarcón, Madrid, Spain.|IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
authors.forename: Mariam
authors.initials: M
authors.lastname: Vázquez
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.
authors.forename: Ermelinda
authors.initials: E
authors.lastname: Lomazzo
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.
authors.forename: Clementine
authors.initials: C
authors.lastname: Hofmann
authors.affiliation: Departamento de Psicobiología. Facultad de Psicología, Universidad Complutense de Madrid. Campus de Somosaguas s/n, Pozuelo de Alarcón, Madrid, Spain.
authors.forename: Rosario Noemi
authors.initials: RN
authors.lastname: Blanco
authors.affiliation: Departamento de Psicobiología. Facultad de Psicología, Universidad Complutense de Madrid. Campus de Somosaguas s/n, Pozuelo de Alarcón, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Alén
authors.affiliation: Departamento de Psicobiología. Facultad de Psicología, Universidad Complutense de Madrid. Campus de Somosaguas s/n, Pozuelo de Alarcón, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Antón
authors.affiliation: IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Decara
authors.affiliation: IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Arco
authors.affiliation: Departamento de Psicobiología. Facultad de Psicología, Universidad Complutense de Madrid. Campus de Somosaguas s/n, Pozuelo de Alarcón, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Orio
authors.affiliation: IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.|Departamento de Biología Celular, Genética y Fisiología. IBIMA. Facultad de Ciencias, Universidad de Malaga. Campus de Teatinos s/n, Malaga, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Suárez
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.affiliation: Departamento de Psicobiología. Facultad de Psicología, Universidad Complutense de Madrid. Campus de Somosaguas s/n, Pozuelo de Alarcón, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Gómez de Heras
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Bindila
authors.affiliation: Departamento de Psicobiología. Facultad de Psicología, Universidad Complutense de Madrid. Campus de Somosaguas s/n, Pozuelo de Alarcón, Madrid, Spain.|IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
authors.forename: Fernando
authors.identifier: http://orcid.org/0000-0002-4516-5795
authors.initials: F
authors.lastname: Rodríguez de Fonseca
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D031204:Caloric Restriction / Q000379:methods; D063388:Endocannabinoids / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000254:growth & development*; D007031:Hypothalamus / Q000254:growth & development*; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D008297:Male; D009830:Olfactory Bulb / Q000254:growth & development*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D063388:Endocannabinoids; D008055:Lipids