Expression of Functional Cannabinoid Type-1 (CB₁) Receptor in Mitochondria of White Adipocytes

Via activation of the cannabinoid type-1 (CB₁) receptor, endogenous and exogenous cannabinoids modulate important biochemical and cellular processes in adipocytes. Several pieces of evidence suggest that alterations of mitochondrial physiology might be a possible mechanism underlying cannabinoids' effects on adipocyte biology. Many reports suggest the presence of CB₁ receptor mRNA in both white and brown adipose tissue, but the detailed subcellular localization of CB₁ protein in adipose cells has so far been scarcely addressed. In this study, we show the presence of the functional CB₁ receptor at different subcellular locations of adipocytes from epididymal white adipose tissue (eWAT) depots. We observed that CB₁ is located at different subcellular levels, including the plasma membrane and in close association with mitochondria (mtCB₁). Functional analysis in tissue homogenates and isolated mitochondria allowed us to reveal that cannabinoids negatively regulate complex-I-dependent oxygen consumption in eWAT. This effect requires mtCB₁ activation and consequent regulation of the intramitochondrial cAMP-PKA pathway. Thus, CB₁ receptors are functionally present at the mitochondrial level in eWAT adipocytes, adding another possible mechanism for peripheral regulation of energy metabolism.