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Am J Physiol Endocrinol Metab. 2018 Apr 1;314(4):E322-E333. doi: 10.1152/ajpendo.00119.2017. Epub 2017 Nov 14.

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

Author information

1
School of Medicine, Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center at the Permian Basin , Odessa, Texas.
2
Department of Animal Science, University of Wyoming , Laramie, Wyoming.
3
Texas Biomedical Research Institute and Southwest National Primate Research Center , San Antonio, Texas.
4
School of Pharmacy, Texas Tech University Health Sciences Center , Amarillo, Texas.
5
University of Alabama at Birmingham , Birmingham, Alabama.
6
Clinical Research Institute, Texas Tech University Health Sciences , Lubbock, Texas.

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.

KEYWORDS:

endogenous cannabinoids; high-fat diet; liver; placenta; pregnancy

PMID:
29138223
PMCID:
PMC5966752
[Available on 2019-04-01]
DOI:
10.1152/ajpendo.00119.2017
[Indexed for MEDLINE]

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