# Overactivation of the Endocannabinoid System in Adolescence Disrupts Adult Adipose Organ Function in Mice

## TL;DR

Adolescent THC exposure in mice leads to long-term changes in fat tissue function, resulting in a lean but metabolically unhealthy state in adulthood.

## Contribution

The study proposes that adolescent THC exposure causes lasting adipocyte dysfunction, not just receptor desensitization.

## Key findings

- Adolescent THC exposure in mice reduces adult fat mass and increases resistance to obesity and dyslipidemia.
- THC exposure leads to impaired thermogenesis and lipolysis in adulthood, linked to overexpression of myocyte proteins in adipose tissue.
- The observed metabolic state resembles healthy leanness but is associated with adipocyte dysfunction.

## Abstract

Cannabis use stimulates calorie intake, but epidemiological studies show that people who regularly use it are leaner than those who don’t. Two explanations have been proposed for this paradoxical finding. One posits that Δ9-tetrahydrocannabinol (THC) in cannabis desensitizes adipose CB1 cannabinoid receptors, stopping their stimulating effects on lipogenesis and adipogenesis. Another explanation is that THC exposure in adolescence, when habitual cannabis use typically starts, produces lasting changes in the developing adipose organ, which impacts adult systemic energy use. Here, we consider these possibilities in the light of a study which showed that daily THC administration in adolescent mice produces an adult metabolic phenotype characterized by reduced fat mass, partial resistance to obesity and dyslipidemia, and impaired thermogenesis and lipolysis. The phenotype, whose development requires activation of CB1 receptors in differentiated adipocytes, is associated with overexpression of myocyte proteins in the adipose organ with unchanged CB1 expression. We propose that adolescent exposure to THC causes lasting adipocyte dysfunction and the consequent emergence of a metabolic state that only superficially resembles healthy leanness. A corollary of this hypothesis, which should be addressed in future studies, is that CB1 receptors and their endocannabinoid ligands may contribute to the maintenance of adipocyte differentiation during adolescence.