Sex differences in the effects of maternal voluntary oral cannabis
consumption on the metabolic outcomes of high fat diet in adult
offspring
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.