1. Adolescent exposure to low-dose THC disrupts energy balance and adipose organ homeostasis in adulthood
- Author
-
Lin, Lin, Jung, Kwang-Mook, Lee, Hye-Lim, Le, Johnny, Colleluori, Georgia, Wood, Courtney, Palese, Francesca, Squire, Erica, Ramirez, Jade, Su, Shiqi, Torrens, Alexa, Fotio, Yannick, Tang, Lingyi, Yu, Clinton, Yang, Qin, Huang, Lan, DiPatrizio, Nicholas, Jang, Cholsoon, Cinti, Saverio, and Piomelli, Daniele
- Subjects
Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Cannabinoid Research ,Drug Abuse (NIDA only) ,Nutrition ,Obesity ,Substance Misuse ,Pediatric ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Mice ,Male ,Animals ,Dronabinol ,Adiposity ,Energy Intake ,Homeostasis ,2-arachidonoylglycerol ,adipocyte ,anandamide ,cannabis ,endocannabinoids ,Biochemistry and Cell Biology ,Medical Biochemistry and Metabolomics ,Endocrinology & Metabolism ,Biochemistry and cell biology ,Medical biochemistry and metabolomics - 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.
- Published
- 2023