%A Ramírez-López,María T. %A Arco,Rocío %A Decara,Juan %A Vázquez,Mariam %A Rivera,Patricia %A Blanco,Rosario Noemi %A Alén,Francisco %A Gómez de Heras,Raquel %A Suárez,Juan %A Rodríguez de Fonseca,Fernando %D 2016 %J Frontiers in Behavioral Neuroscience %C %F %G English %K maternal diet,food restriction,CB1 receptor,β-oxidation,Lipoproteins,Lipogenesis,Hypothalamus,Liver,Adipose Tissue,Feeding Behavior %Q %R 10.3389/fnbeh.2016.00241 %W %L %M %P %7 %8 2016-December-27 %9 Original Research %+ Dr Juan Suárez,Instituto de Investigación Biomédica de Málaga (IBIMA), Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga,Málaga, Spain,juan.suarez@uma.es %+ Dr Juan Suárez,Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA), Facultad de Ciencias, Universidad de Málaga,Málaga, Spain,juan.suarez@uma.es %+ Prof Fernando Rodríguez de Fonseca,Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid,Madrid, Spain,fernando.rodriguez@ibima.eu %+ Prof Fernando Rodríguez de Fonseca,Instituto de Investigación Biomédica de Málaga (IBIMA), Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga,Málaga, Spain,fernando.rodriguez@ibima.eu %# %! IMPACT OF MATERNAL UNDERNUTRITION ON THE ENDOGENOUS CANNABINOID SYSTEM %* %< %T 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 %U https://www.frontiersin.org/articles/10.3389/fnbeh.2016.00241 %V 10 %0 JOURNAL ARTICLE %@ 1662-5153 %X 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.