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Sex differences in the effects of maternal voluntary oral cannabis consumption on the metabolic outcomes of high fat diet in adult offspring
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  • Nada Sallam,
  • Colleen Peterson,
  • Samaa Kamar,
  • Camile Saenz,
  • Frank Visser,
  • Stephanie Borgland
Nada Sallam
Cairo University Faculty of Pharmacy
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Colleen Peterson
University of Calgary Cumming School of Medicine
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Samaa Kamar
Cairo University
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Camile Saenz
University of Calgary Cumming School of Medicine
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Frank Visser
University of Calgary Cumming School of Medicine
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Stephanie Borgland
University of Calgary Cumming School of Medicine

Corresponding Author:[email protected]

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Abstract

Background and Purpose: Given the recent rise in cannabis legalization, accessibility and consumption by pregnant individuals, there are unintended developmental consequences considering the key role that the endocannabinoid system plays in fetal development and later-life energy homeostasis. Whether perinatal cannabis exposure (PCE) affects energy homeostasis positively or adversely in adulthood is unknown. We explored the long-term effects of maternal voluntary oral cannabis consumption on the metabolic outcomes of high fat diet (HFD) in adult offspring. Experimental Approach: Pregnant mice voluntarily consumed cannabis from gestational day 1.5 until postnatal day (PD) 10. Pregnancy and pup outcomes and active maternal behavior were recorded. Male and female offspring (PD49) were placed on a 12-week HFD or control diet; their weight gain, adiposity, glucose tolerance, insulin sensitivity, circulating hormones, and pancreas structure were measured. Key Results: PCE pup weight was reduced but was restored by PD16. PCE did not influence weight gain or metabolic characteristics of male mice on a HFD. However, PCE female offspring on a HFD had reduced accumulation of adipose tissue and lower insulin, leptin, and resistin independent of body weight and while PCE females on control diet showed altered basal insulin sensitivity likely due to increased glucagon levels in parallel with reduced islets of Langerhans size and enhanced gene expression of cannabinoid 2 receptors in white adipose tissue. Conclusion and Implications: PCE influences metabolic outcomes in female offspring; it adversely affected glycemic control in female offspring on control diet while it mitigated HFD-induced metabolic dysfunction. This raises concerns about the long-term effects of PCE on the metabolic health of offspring.
Submitted to British Journal of Pharmacology
Assigned to Editor
Reviewer(s) Assigned
Submission Checks Completed
23 Jun 2024Review(s) Completed, Editorial Evaluation Pending
29 Jun 2024Reviewer(s) Assigned
23 Aug 2024Editorial Decision: Revise Minor