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

Via activation of the cannabinoid type-1 (CB(1)) 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 CB(1) receptor mRNA in both white and brown adipose tissue, but the detailed subcellular localization of CB(1) protein in adipose cells has so far been scarcely addressed. In this study, we show the presence of the functional CB(1) receptor at different subcellular locations of adipocytes from epididymal white adipose tissue (eWAT) depots. We observed that CB(1) is located at different subcellular levels, including the plasma membrane and in close association with mitochondria (mtCB(1)). 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 mtCB(1) activation and consequent regulation of the intramitochondrial cAMP-PKA pathway. Thus, CB(1) receptors are functionally present at the mitochondrial level in eWAT adipocytes, adding another possible mechanism for peripheral regulation of energy metabolism.