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 Ramirez-Lopez, Maria T.
A1 Arco, Rocio
A1 Decara, Juan
A1 Vazquez, Mariam
A1 Rivera, Patricia
A1 Noemi Blanco, Rosario
A1 Alen, Francisco
A1 Gomez de Heras, Raquel
A1 Suarez, Juan
A1 Rodriguez de Fonseca, Fernando
K1 maternaldiet
K1 CB1receptor
K1 beta-oxidation
K1 lipoproteins
K1 lipogenesis
K1 hypothalamus
K1 liver
K1 adipose tissue
K1 Monoglyceride lipase deficiency
K1 Moderate caloric restriction
K1 Maternal dietary restriction
K1 Ppar-alpha agonist
K1 Low birth-weight
K1 Low-protein diet
K1 Cb1 receptors
K1 Body-weight
K1 Periconceptional period
K1 Developmental origins
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, Dagl alpha, Mgll) and several key regulators of fatty-acid beta-oxidation (Cptl b, Acox1), mitochondrial respiration (Cox4i1), and lipid flux (Pear gamma) 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, Ppar alpha, Ppar gamma, the eCBs-degrading enzymes Faah and Mg11, the de novo lipogenic enzymes Acaca and Fasn, and the liver-specific cholesterol biosynthesis regulators insigl and Hrngcr. Our results suggest that the long-lasting adaptive responses to maternal caloric restriction affected cannabinoid-regulated mechanisms involved in feeding behavior, adipose beta-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 http://hdl.handle.net/10668/19229
UL http://hdl.handle.net/10668/19229
LA en
DS RISalud
RD Apr 6, 2025