Effect of maternal high-fat diet on key components of the placental and hepatic endocannabinoid system

Abstract

Maternal obesity in pregnancy has been linked to a spectrum of adverse developmental changes. Involvement of eCBs in obesity is well characterized. However, information regarding eCB physiology in obesity associated with pregnancy is sparse. This study evaluated fetomaternal hepatic, systemic, and placental eCB molecular changes in response to maternal consumption of a HFD. From ≥9 mo before conception, nonpregnant baboons ( Papio spp.) were fed a diet of either 45 (HFD; n = 11) or 12% fat or a control diet (CTR; n = 11), and dietary intervention continued through pregnancy. Maternal and fetal venous plasma samples were evaluated using liquid chromatography-mass spectrometry to quantify AEA and 2-AG. Placental, maternal and fetal hepatic tissues were analyzed using RT-PCR, Western blot, and immunohistochemistry. mRNA and protein expression of endocannabinoid receptors (CB1R and CB2R), FAAH, DAGL, MAGL, and COX-2 were determined. Statistical analyses were performed with the nonparametric Scheirer-Ray-Hare extension of the Kruskal-Wallis test to analyze the effects of diet (HFD vs. CTR), fetal sex (male vs. female), and the diet × sex interaction. Fetal weight was influenced by fetal sex but not by maternal diet. The increase in maternal weight in animals fed the HFD vs. the CTR diet approached significance ( P = 0.055). Maternal circulating 2-AG concentrations increased, and fetal circulating concentrations decreased in the HFD group, independently of fetal sex. CB1R receptor expression was detected in syncytiotrophoblasts (HFD) and the fetal endothelium (CTR and HFD). Placental CB2R protein expression was higher in males and lower in female fetuses in the HFD group. Fetal hepatic CB2R, FAAH, COX-2 (for both fetal sexes), and DAGLα (in male fetuses) protein expression decreased in the HFD group compared with the CTR group. We conclude that consumption of a HFD during pregnancy results in fetal systemic 2-AG and hepatic eCB deficiency.

Maternal high-fat diet consumption induces sex-dependent alterations of the endocannabinoid system and redox homeostasis in liver of adult rat offspring

“…However, of note, the present study focused on the regulation of the protein content of ECS components instead of transcript levels. Another study recently published by Gandhi et al ., showed that maternal HF diet in baboons decreases CB2 and FAAH protein content in fetal liver, but the impact of ECS changes on liver morphology and function was not investigated 48 . The different profiles found in liver ECS among these studies may arise from different ages and species used in the experiments.…”

Analysis of Both Lipid Metabolism and Endocannabinoid Signaling Reveals a New Role for Hypothalamic Astrocytes in Maternal Caloric Restriction-Induced Perinatal Programming

“…Despite the evident role of the ECS in neurodevelopment, there are few studies on the implication of the endocannabinoid system in perinatal programming, most of which have focused on a hypercaloric diet and the alteration of cannabinoid receptors in the short and long term in offspring, specifically in the brain and peripheral tissues [13,[44][45][46][47][48].…”

Quality of Life and a Surveillant Endocannabinoid System

“…The tonus of the ECS in the brain and peripheral tissues may be modulated by unappropriated parental life style and environmental conditions (nutrition, toxicant exposure, and stress) during the perinatal period and adolescence, predisposing offspring to metabolic and behavioral disorders throughout life (Figure 6; Lopez-Gallardo et al, 2012;Stringer et al, 2013;Ramirez-Lopez et al, 2015, 2016aRomano-Lopez et al, 2016;Almeida et al, 2017Almeida et al, , 2019Almeida et al, , 2020Dias-Rocha et al, 2018;Gandhi et al, 2018;Miranda et al, 2018;de Oliveira et al, 2019;Soares et al, 2019;Rivera et al, 2020). This phenomenon is known as "metabolic programming" or "ontogenetic plasticity" and involves epigenetic regulation of gene expression (Brenseke et al, 2013;Lillycrop and Burdge, 2015;Gluckman et al, 2019).…”

“…Maternal high-fat (45% fat) diet decreases serum levels of eCBs in baboon offspring at birth (Gandhi et al, 2018). In rats, a maternal hypercaloric-low protein diet (6% protein, 24% fat) decreases hypothalamic endocannabinoid levels only in newborn male offspring, while decreases the preference for a chocolate diet and induces anxiety-like behavior in these animals in adulthood (Ramirez-Lopez et al, 2015, 2016a.…”