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Animal Models

Effects of prenatal THC vapor exposure on body weight, glucose metabolism, and feeding behaviors in chow and high-fat diet fed rats

International Journal of Obesity (2024)Cite this article

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Abstract

Background

4−20% of people report using cannabis during pregnancy, thereby it is essential to assess the associated risks. There is some evidence that prenatal cannabis exposure (PCE) may be associated with increased risk for developing of obesity and diabetes later in life, however this has not been well explored under controlled conditions. The aim of this study was to use a translational THC vapor model in rodents to characterize the effects of PCE on adiposity, glucose metabolism, and feeding patterns in adulthood, with focus on potential sex differences.

Methods

Pregnant Sprague Dawley rats were exposed to vaporized THC (100 mg/ml) or control (polyethylene glycol vehicle) across the entire gestational period. Adult offspring from PCE (n = 24) or control (n = 24) litters were subjected to measures of adiposity, glucose metabolism and feeding behavior. Rats were then placed onto special diets (60% high-fat diet [HFD] or control 10% low fat diet [LFD]) for 4-months, then re-subjected to adiposity, glucose metabolism and feeding behavior measurements.

Results

PCE did not influence maternal weight or food consumption but was associated with transient decreased pup weight. PCE did not initially influence bodyweight or adiposity, but PCE did significantly reduce the rate of bodyweight gain when on HFD/LFD, regardless of which diet. Further, PCE had complex effects on glucose metabolism and feeding behavior that were both sex and diet dependent. No effects of PCE were found on plasma leptin or insulin, or white adipose tissue mass.

Conclusions

PCE may not promote obesity development but may increase risk for diabetes and abnormal eating habits under certain biological and environmental conditions. Overall, this data enhances current understanding of the potential impacts of PCE.

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Fig. 1: In chow-fed offspring, PCE has no effect on bodyweight gain, but improves glucose tolerance and increases 24-hr chow intake.
Fig. 2: In chow-fed offspring, PCE increases acute (2-h) high-carbohydrate food intake when given a food choice, an effect that is prolonged by stress.
Fig. 3: With HFD or LFD access, PCE reduces bodyweight gain over time irrespective of diet but has no effect on energy intake.
Fig. 4: In HFD/LFD-fed offspring, PCE has bi-directional, sex-dependent effects on glucose metabolism, further disrupting glucose metabolism in males and improving glucose metabolism in females.
Fig. 5: In HFD/LFD-fed offspring, PCE has no effect on energy intake patterns or food choice but reduces sucrose preference.

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Data availability

The datasets generated and/or analysed in this manuscript are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to acknowledge that Indigenous peoples are the original and current caretakers of the land we live, work, learn, and play on. Specifically, our research was conducted on the traditional territories of the people of the Treaty 7 region in Southern Alberta, which includes the Blackfoot Confederacy (comprising the Siksika, Piikani, and Kainai First Nations), as well as the Tsuut’ina First Nation, and the Stoney Nakoda (including the Chiniki, Bearspaw, and Wesley First Nations). The City of Calgary is also home to Métis Nation of Alberta (District 5 and 6). As an academic community, we must recognize that their land was taken through coercive and violent acts, and we must support their authority and rights over this stolen land. We must acknowledge our responsibility to establish and maintain relationships with Indigenous peoples and we must include their voices in our teaching and research. We would also like to thank Dr Lauren Seabrook for advice and assistance with data analysis and glucose tolerance testing; Dr Georgia Balsevich for experimental design advice; and finally Andrei (Sabin) Nastase, Dr Robert Aukema and Dr Gavin Petrie for data collection help.

Funding

This research is funded by operating funds from the Canadian Institutes of Health Research (CIHR) held by MNH. CH received salary support from a Hotchkiss Brain Institute (HBI) Harley Hotchkiss - Samuel Weiss Postdoctoral Fellowship, Alberta Children’s Hospital Research Institute (ACHRI) Postdoctoral Fellowship and Cumming School of Medicine Postdoctoral Fellowship. SLB received salary support from an ACHRI Graduate Scholarship, Brain Canada Rising Stars Trainee Award: CCIC Neuroscience Fellowship in Cannabis and Cannabinoid Research and Alberta Graduate Excellence Scholarship (AGES) – Indigenous. LJ received salary support from an Alberta Innovates Summer Research Studentship. SHML received salary support from a HBI Harley N Hotchkiss Graduate Scholarship in Neuroscience and AGES – Indigenous. JS received salary support from a CIHR Canada Graduate Scholarship – Master’s and HBI Graduate Scholarship in Neuroscience.

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Author notes

  1. These authors contributed equally: Catherine Hume, Samantha L. Baglot.

Authors and Affiliations

  1. Hotchkiss Brain Institute | Mathison Centre for Mental Health Research & Education | Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada

    Catherine Hume, Samantha L. Baglot, Lucia Javorcikova, Savannah H. M. Lightfoot, Jessica Scheufen & Matthew N. Hill

  2. Department of Cell Biology & Anatomy | Department of Psychiatry, University of Calgary, Calgary, AB, Canada

    Catherine Hume & Matthew N. Hill

  3. Graduate Program in Neuroscience, University of Calgary, Calgary, AB, Canada

    Samantha L. Baglot, Lucia Javorcikova, Savannah H. M. Lightfoot & Jessica Scheufen

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  1. Catherine Hume
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Contributions

Conceptualization and experimental design were carried out by CH, SLB and MNH. Breeding and PCE was carried out by SLB and SHML, with help from LJ and CH. Feeding behavior experiments were carried out by CH with help from LJ, SLB and JS. Glucose tolerance tests were carried out by CH and SLB with help from LJ, JS and SHML. WAT measurements, blood sampling and ELISA’s were carried out by CH and SLB. CH and SLB analyzed data and wrote the manuscript with help from LJ and MNH. All authors read and approved the manuscript.

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Correspondence to Catherine Hume or Matthew N. Hill.

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Hume, C., Baglot, S.L., Javorcikova, L. et al. Effects of prenatal THC vapor exposure on body weight, glucose metabolism, and feeding behaviors in chow and high-fat diet fed rats. Int J Obes (2024). https://doi.org/10.1038/s41366-024-01512-8

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