Exposure to a Highly Caloric Palatable Diet during the Perinatal Period Affects the Expression of the Endogenous Cannabinoid System in the Brain, Liver and Adipose Tissue of Adult Rat Offspring

Ramírez-López, María Teresa; Arco, Raquel; Decara, Juan; Vázquez, Margarita González; Blanco, Rosario Noemí; Alén, Francisco; Suárez, Juan; Heras, Raquel Gómez de; Fonseca, Fernando Rodrı́guez de

doi:10.1371/journal.pone.0165432

Cited by 25 publications

(25 citation statements)

References 92 publications

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“…However, this increase in body weight was not accompanied by an increase in inflammatory responses. Hepatic Cnr1 expression was not affected, whereas hepatic faah mRNA expression was decreased in the female offspring that were exposed prenatally to a HFD in a rodent model (67). In agreement with these data, FAAH protein expression was decreased in the fetal liver of HFD dams in our study.…”

Section: Fetal Hepatic Ecbs and Maternal Consumption Of Hfdsupporting

confidence: 91%

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

Gandhi

German

et al. 2018

American Journal of Physiology-Endocrinology and Metabolism

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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.

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Section: Fetal Hepatic Ecbs and Maternal Consumption Of Hfdsupporting

confidence: 91%

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

Gandhi

German

et al. 2018

American Journal of Physiology-Endocrinology and Metabolism

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“…Based on the results in this study, the reduction in fetal growth are likely attributable to impaired placental function, however, as Δ9-THC has been shown to cross the placenta, it is worth considering that Δ9-THC binding to the CB1R/CB2R in the fetal liver and brain may also have an impact 12,82,100,108 . The current study is limited in its scope and independent studies will need to be conducted to evaluate the post-natal onset of MetS along with an in-depth evaluation of the placenta vascular pathology.…”

Section: Discussionmentioning

confidence: 92%

Δ9-tetrahydrocannabinol exposure during rat pregnancy leads to symmetrical fetal growth restriction and labyrinth-specific vascular defects in the placenta

Natale

Gustin

Lee

et al. 2020

Sci Rep

145

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1 in 5 women report cannabis use during pregnancy, with nausea cited as their primary motivation. Studies show that (-)-△9-tetrahydrocannabinol (Δ9-THC), the major psychoactive ingredient in cannabis, causes fetal growth restriction, though the mechanisms are not well understood. Given the critical role of the placenta to transfer oxygen and nutrients from mother, to the fetus, any compromise in the development of fetal-placental circulation significantly affects maternal-fetal exchange and thereby, fetal growth. The goal of this study was to examine, in rats, the impact of maternal Δ9-THC exposure on fetal development, neonatal outcomes, and placental development. Dams received a daily intraperitoneal injection (i.p.) of vehicle control or Δ9-THC (3 mg/kg) from embryonic (E)6.5 through 22. Dams were allowed to deliver normally to measure pregnancy and neonatal outcomes, with a subset sacrificed at E19.5 for placenta assessment via immunohistochemistry and qPCR. Gestational Δ9-THC exposure resulted in pups born with symmetrical fetal growth restriction, with catch up growth by postnatal day (PND)21. During pregnancy there were no changes to maternal food intake, maternal weight gain, litter size, or gestational length. E19.5 placentas from Δ9-THC-exposed pregnancies exhibited a phenotype characterized by increased labyrinth area, reduced Epcam expression (marker of labyrinth trophoblast progenitors), altered maternal blood space, decreased fetal capillary area and an increased recruitment of pericytes with greater collagen deposition, when compared to vehicle controls. Further, at E19.5 labyrinth trophoblast had reduced glucose transporter 1 (GLUT1) and glucocorticoid receptor (GR) expression in response to Δ9-THC exposure. In conclusion, maternal exposure to Δ9-THC effectively compromised fetal growth, which may be a result of the adversely affected labyrinth zone development. These findings implicate GLUT1 as a Δ9-THC target and provide a potential mechanism for the fetal growth restriction observed in women who use cannabis during pregnancy. Over the last decade, cannabis use has progressively increased in pregnant women, in part due to the perception that its usage poses no risk in perinatal life 1,2. In the United States, the rates of self-reported or screened cannabis use in pregnant mothers (18-24 years) varies from 6 to 22%, with some women admitting to daily use 2,3. Of great concern is that cannabis use in pregnancy is more prevalent in young, urban, socially disadvantaged women 4,5 .

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“…Similarly, Ramirez-Lopez and colleagues reported reductions at birth in levels of the eCBs, AEA and 2-AG, in the hypothalamus of male rats born from mothers maintained on a high-calorie test diet versus standard chow during the pregestational and gestational periods [ 54 ]. Furthermore, rats born to mothers maintained on either a palatable chocolate diet in combination with standard chow (ad-libitum access to both) or control rats given access to only standard chow for 8 weeks displayed very small decreases in body weight gain over a period of nineteen weeks [ 16 ]. The authors then analyzed expression of eCB system components in brain, liver, and adipose tissue in these rats at nineteen weeks postnatal and found a variety of sex-specific changes in expression of mRNA for several components of the eCB system (see for details [ 16 ]).…”

Section: Discussionmentioning

confidence: 99%

Impact of maternal western diet-induced obesity on offspring mortality and peripheral endocannabinoid system in mice

Perez

DiPatrizio

2018

PLoS ONE

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Over two-thirds of adults in the United States are obese or overweight, which is largely due to chronic overconsumption of diets high in fats and sugars (i.e., Western diet). Recent studies reveal that maternal obesity may predispose offspring to development of obesity and other metabolic diseases; however, the molecular underpinnings of these outcomes are largely unknown. The endocannabinoid system is an important signaling pathway that controls feeding behavior and energy homeostasis, and its activity becomes upregulated in the upper small intestinal epithelium of Western diet-induced obese mice, which drives overeating. In the current investigation, we examined the impact of chronic maternal consumption of Western diet on the expression and function of the endocannabinoid system in several peripheral organs important for food intake and energy homeostasis in offspring. Female C57BL/6Tac mice were fed a Western diet or low-fat/no-sucrose control chow for 10 weeks, then males were introduced for mating. Dams were maintained on their respective diets through weaning of pups, at which time pups were maintained on low-fat/no-sucrose chow for 10 weeks. Neonates born from dams fed Western diet, when compared to those born from mice fed control chow, unexpectedly displayed increases in mortality that occurred exclusively within six days following birth (greater than 50% mortality). Males comprised a larger fraction of surviving offspring from obese dams. Furthermore, surviving offspring displayed transient increases in body mass for first two days post weaning, and no marked changes in feeding patterns and endocannabinoid levels in upper small intestinal epithelium, pancreas, and plasma, or in expression of key endocannabinoid system genes in the upper small intestinal epithelium and pancreas at 10 weeks post-weaning. Collectively, these results suggest that maternal diet composition greatly influences survival of neonate C57BL/6Tac mice, and that surviving offspring from dams chronically fed a Western diet do not display marked changes in body mass, eating patterns, or expression and function of the endocannabinoid system in several peripheral organs important for feeding behavior and energy homeostasis.

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Exposure to a Highly Caloric Palatable Diet during the Perinatal Period Affects the Expression of the Endogenous Cannabinoid System in the Brain, Liver and Adipose Tissue of Adult Rat Offspring

Cited by 25 publications

References 92 publications

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

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

Δ9-tetrahydrocannabinol exposure during rat pregnancy leads to symmetrical fetal growth restriction and labyrinth-specific vascular defects in the placenta

Impact of maternal western diet-induced obesity on offspring mortality and peripheral endocannabinoid system in mice

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