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 T
A1 Arco, Rocío
A1 Decara, Juan
A1 Vázquez, Mariam
A1 Rivera, Patricia
A1 Blanco, Rosario Noemi
A1 Alén, Francisco
A1 Gómez de Heras, Raquel
A1 Suárez, Juan
A1 Rodríguez de Fonseca, Fernando
K1 CB1 receptor
K1 adipose tissue
K1 hypothalamus
K1 lipogenesis
K1 lipoproteins
K1 liver
K1 maternal diet
K1 β-oxidation
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.
SN 1662-5153
YR 2016
FD 2016-12-27
LK https://hdl.handle.net/10668/27727
UL https://hdl.handle.net/10668/27727
LA en
DS RISalud
RD Apr 4, 2025