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Article

In Utero Exposure to Δ9-Tetrahydrocannabinol Leads to Postnatal Catch-Up Growth and Dysmetabolism in the Adult Rat Liver

1
Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street, London, ON N6A 5C1, Canada
2
The Children’s Health Research Institute, The Lawson Health Research Institute, London, ON N6A 5C1, Canada
3
Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street, London, ON N6A 5C1, Canada
4
Department of Obstetrics and Gynaecology, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street, London, ON N6A 5C1, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Deanne H. Hryciw
Int. J. Mol. Sci. 2021, 22(14), 7502; https://doi.org/10.3390/ijms22147502
Received: 29 June 2021 / Revised: 10 July 2021 / Accepted: 11 July 2021 / Published: 13 July 2021
The rates of gestational cannabis use have increased despite limited evidence for its safety in fetal life. Recent animal studies demonstrate that prenatal exposure to Δ9-tetrahydrocannabinol (Δ9-THC, the psychoactive component of cannabis) promotes intrauterine growth restriction (IUGR), culminating in postnatal metabolic deficits. Given IUGR is associated with impaired hepatic function, we hypothesized that Δ9-THC offspring would exhibit hepatic dyslipidemia. Pregnant Wistar rat dams received daily injections of vehicular control or 3 mg/kg Δ9-THC i.p. from embryonic day (E) 6.5 through E22. Exposure to Δ9-THC decreased the liver to body weight ratio at birth, followed by catch-up growth by three weeks of age. At six months, Δ9-THC-exposed male offspring exhibited increased visceral adiposity and higher hepatic triglycerides. This was instigated by augmented expression of enzymes involved in triglyceride synthesis (ACCα, SCD, FABP1, and DGAT2) at three weeks. Furthermore, the expression of hepatic DGAT1/DGAT2 was sustained at six months, concomitant with mitochondrial dysfunction (i.e., elevated p66shc) and oxidative stress. Interestingly, decreases in miR-203a-3p and miR-29a/b/c, both implicated in dyslipidemia, were also observed in these Δ9-THC-exposed offspring. Collectively, these findings indicate that prenatal Δ9-THC exposure results in long-term dyslipidemia associated with enhanced hepatic lipogenesis. This is attributed by mitochondrial dysfunction and epigenetic mechanisms. View Full-Text
Keywords: Δ9-tetrahydrocannabinol; intrauterine growth restriction; liver; metabolism; triglycerides; oxidative stress; mitochondria; miR-203a-3p; miR-29a/b/c Δ9-tetrahydrocannabinol; intrauterine growth restriction; liver; metabolism; triglycerides; oxidative stress; mitochondria; miR-203a-3p; miR-29a/b/c
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MDPI and ACS Style

Oke, S.L.; Lee, K.; Papp, R.; Laviolette, S.R.; Hardy, D.B. In Utero Exposure to Δ9-Tetrahydrocannabinol Leads to Postnatal Catch-Up Growth and Dysmetabolism in the Adult Rat Liver. Int. J. Mol. Sci. 2021, 22, 7502. https://doi.org/10.3390/ijms22147502

AMA Style

Oke SL, Lee K, Papp R, Laviolette SR, Hardy DB. In Utero Exposure to Δ9-Tetrahydrocannabinol Leads to Postnatal Catch-Up Growth and Dysmetabolism in the Adult Rat Liver. International Journal of Molecular Sciences. 2021; 22(14):7502. https://doi.org/10.3390/ijms22147502

Chicago/Turabian Style

Oke, Shelby L., Kendrick Lee, Rosemary Papp, Steven R. Laviolette, and Daniel B. Hardy 2021. "In Utero Exposure to Δ9-Tetrahydrocannabinol Leads to Postnatal Catch-Up Growth and Dysmetabolism in the Adult Rat Liver" International Journal of Molecular Sciences 22, no. 14: 7502. https://doi.org/10.3390/ijms22147502

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