Adolescent exposure to low-dose THC disrupts energy balance and adipose organ homeostasis in adulthood

Cell Metab. 2023 Jul 11;35(7):1227-1241.e7. doi: 10.1016/j.cmet.2023.05.002. Epub 2023 Jun 1.

Abstract

One of cannabis' most iconic effects is the stimulation of hedonic high-calorie eating-the "munchies"-yet habitual cannabis users are, on average, leaner than non-users. We asked whether this phenotype might result from lasting changes in energy balance established during adolescence, when use of the drug often begins. We found that daily low-dose administration of cannabis' intoxicating constituent, Δ9-tetrahydrocannabinol (THC), to adolescent male mice causes an adult metabolic phenotype characterized by reduced fat mass, increased lean mass and utilization of fat as fuel, partial resistance to diet-induced obesity and dyslipidemia, enhanced thermogenesis, and impaired cold- and β-adrenergic receptor-stimulated lipolysis. Further analyses revealed that this phenotype is associated with molecular anomalies in the adipose organ, including ectopic overexpression of muscle-associated proteins and heightened anabolic processing. Thus, adolescent exposure to THC may promote an enduring "pseudo-lean" state that superficially resembles healthy leanness but might in fact be rooted in adipose organ dysfunction.

Keywords: 2-arachidonoylglycerol; adipocyte; anandamide; cannabis; endocannabinoids.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adiposity
  • Animals
  • Dronabinol* / pharmacology
  • Energy Intake
  • Homeostasis
  • Male
  • Mice
  • Obesity*

Substances

  • Dronabinol