Exposure to a Highly Caloric Palatable Diet during the Perinatal Period Affects the Expression of the Endogenous Cannabinoid System in the Brain, Liver and Adipose Tissue of Adult Rat Offspring.
Recent studies have linked gestational exposure to highly caloric diets with a disrupted endogenous cannabinoid system (ECS). In the present study, we have extended these studies by analyzing the impact of the exposure to a palatable diet during gestation and lactation on a) the adult expression of endocannabinoid-related behaviors, b) the metabolic profile of adult offspring and c) the mRNA expression of the signaling machinery of the ECS in the hypothalamus, the liver and the adipose tissue of adult offspring of both sexes. Exposure to a palatable diet resulted in a) sex-dimorphic and perinatal diet specific feeding behaviors, including the differential response to the inhibitory effects of the cannabinoid receptor inverse agonist AM251, b) features of metabolic syndrome including increased adiposity, hyperleptinemia, hypertriglyceridemia and hypercholesterolemia and c) tissue and sex-specific changes in the expression of both CB1 and CB2 receptors and in that of the endocannabinoid-degrading enzymes FAAH and MAGL, being the adipose tissue the most affected organ analyzed. Since the effects were observed in adult animals that were weaned while consuming a normal diet, the present results indicate that the ECS is one of the targets of maternal programming of the offspring energy expenditure. These results clearly indicate that the maternal diet has long-term effects on the development of pups through multiple alterations of signaling homeostatic pathways that include the ECS. The potential relevance of these alterations for the current obesity epidemic is discussed.
Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, Campus de Somosaguas s/n, 28223 Pozuelo de Alarcón, Madrid, Spain.
María Teresa
MT
Ramírez-López
Instituto de Investigación Biomédica de Málaga (IBIMA), Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga, 29010, Málaga, Spain.
Raquel
R
Arco
Instituto de Investigación Biomédica de Málaga (IBIMA), Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga, 29010, Málaga, Spain.
Juan
J
Decara
Instituto de Investigación Biomédica de Málaga (IBIMA), Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga, 29010, Málaga, Spain.
Mariam
M
Vázquez
Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, Campus de Somosaguas s/n, 28223 Pozuelo de Alarcón, Madrid, Spain.
Rosario
R
Noemí Blanco
Instituto de Investigación Biomédica de Málaga (IBIMA), Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga, 29010, Málaga, Spain.
Francisco
F
Alén
Instituto de Investigación Biomédica de Málaga (IBIMA), Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga, 29010, Málaga, Spain.
Juan
J
Suárez
Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, Campus de Somosaguas s/n, 28223 Pozuelo de Alarcón, Madrid, Spain.
Raquel
R
Gómez de Heras
Instituto de Investigación Biomédica de Málaga (IBIMA), Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga, 29010, Málaga, Spain.
Fernando
http://orcid.org/0000-0002-4516-5795
F
Rodríguez de Fonseca
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D063388:Endocannabinoids / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011247:Pregnancy; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction / Q000187:drug effects
D063388:Endocannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C103505:AM 251