Mitochondria: a possible nexus for the regulation of energy homeostasis by the endocannabinoid system?. Am J Physiol Endocrinol Metab 307: E1–E13, 2014. First published May 6, 2014; doi:10.1152/ajpendo.00100.2014.—The endocannabinoid system (ECS) regulates numerous cellular and physiological processes through the activation of receptors targeted by endogenously produced ligands called endocannabinoids. Importantly, this signaling system is known to play an important role in modulating energy balance and glucose homeostasis. For example, current evidence indicates that the ECS becomes overactive during obesity whereby its central and peripheral stimulation drives metabolic processes that mimic the metabolic syndrome. Herein, we examine the role of the ECS in modulating the...