Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA 92697, USA.
Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Cell Metab. 2023 Jul 11;35(7):1227-1241.e7. doi: 10.1016/j.cmet.2023.05.002. Epub 2023 Jun 1.
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, Δ-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.
大麻最具标志性的影响之一是促进愉悦的高热量食物摄入,即“饥饿感”,然而习惯性大麻使用者的平均体脂率比非使用者低。我们想知道,这种表型是否可能是由于在青少年时期(此时通常开始使用大麻)建立的能量平衡的持久变化导致的。我们发现,每天给青春期雄性小鼠低剂量施用大麻的致醉成分Δ-四氢大麻酚(THC),会导致成年后的代谢表型,其特征是体脂减少、瘦体重增加和脂肪作为燃料的利用增加、对饮食诱导的肥胖和血脂异常部分有抵抗力、产热增强以及冷和β-肾上腺素能受体刺激的脂肪分解受损。进一步的分析表明,这种表型与脂肪组织中的分子异常有关,包括肌肉相关蛋白的异位过表达和升高的合成代谢处理。因此,青少年时期接触 THC 可能会促进一种持久的“假性瘦”状态,这种状态表面上类似于健康的消瘦,但实际上可能是由脂肪组织功能障碍引起的。