RT Journal Article
T1 Long-Term Effects of Prenatal Exposure to Undernutrition on Cannabinoid Receptor-Related Behaviors: Sex and Tissue-Specific Alterations in the mRNA Expression of Cannabinoid Receptors and Lipid Metabolic Regulators
A1 Ramírez López, María Teresa
A1 Arco, Rocío
A1 Decara, Juan
A1 Vázquez, Mariam
A1 Rivera, Patricia
A1 Blanco, Rosario Noemi
A1 Alén Fariñas, Francisco
A1 Gómez De Heras, María Raquel
A1 Suárez, Juan
A1 Rodríguez de Fonseca, Fernando
AB Maternal malnutrition causes long-lasting alterations in feeding behavior and energy homeostasis in offspring. It is still unknown whether both, the endocannabinoid (eCB) machinery and the lipid metabolism are implicated in long-term adaptive responses to fetal reprogramming caused by maternal undernutrition. We investigated the long-term effects of maternal exposure to a 20% standard diet restriction during preconceptional and gestational periods on the metabolically-relevant tissues hypothalamus, liver, and perirenal fat (PAT) of male and female offspring at adulthood. The adult male offspring from calorie-restricted dams (RC males) exhibited a differential response to the CB1 antagonist AM251 in a chocolate preference test as well as increased body weight, perirenal adiposity, and plasma levels of triglycerides, LDL, VLDL, bilirubin, and leptin. The gene expression of the cannabinoid receptors Cnr1 and Cnr2 was increased in RC male hypothalamus, but a down-expression of most eCBs-metabolizing enzymes (Faah, Daglα, Daglβ, Mgll) and several key regulators of fatty-acid β-oxidation (Cpt1b, Acox1), mitochondrial respiration (Cox4i1), and lipid flux (Pparγ) was found in their PAT. The female offspring from calorie-restricted dams exhibited higher plasma levels of LDL and glucose as well as a reduction in chocolate and caloric intake at post-weaning periods in the feeding tests. Their liver showed a decreased gene expression of Cnr1, Pparα, Pparγ, the eCBs-degrading enzymes Faah and Mgll, the de novo lipogenic enzymes Acaca and Fasn, and the liver-specific cholesterol biosynthesis regulators Insig1 and Hmgcr. Our results suggest that the long-lasting adaptive responses to maternal caloric restriction affected cannabinoid-regulated mechanisms involved in feeding behavior, adipose β-oxidation, and hepatic lipid and cholesterol biosynthesis in a sex-dependent manner.
PB Frontiers Media SA
SN 1662-5153
YR 2016
FD 2016-12-27
LK https://hdl.handle.net/20.500.14352/121784
UL https://hdl.handle.net/20.500.14352/121784
LA eng
NO Ramírez-López MT, Arco R, Decara J, Vázquez M, Rivera P, Blanco RN, et al. Long-term effects of prenatal exposure to undernutrition on cannabinoid receptor-related behaviors: Sex and tissue-specific alterations in the mRNA expression of cannabinoid receptors and lipid metabolic regulators. Frontiers in Behavioral Neuroscience. 2016;10(DEC).
NO Este trabajo fue financiado por el Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, cofinanciado por el programa UE-FEDER (CP12/03109 y PI16/01374 a JS, PI12/02261 a FR, y PSI-2012-35388 a RG), la Red de Trastornos Adictivos (RD12/0028/0001 a FR), CIBERobn, la Consejería de Economía, Innovación y Ciencia de la Junta de Andalucía, UE/FEDER (PI45403, CTS-8221, CTS-433 a FR), la Consejería de Salud de la Junta de Andalucía, UE/FEDER (SAS111224 a JS y FR). MTRL ha sido financiado por 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).
DS Docta Complutense
RD 19 dic 2025