Classical brown adipose tissue (BAT) is a unique type of adipose tissue that is composed of adipocytes with multilocular lipid droplets and a large amount of mitochondria, making it a highly metabolically active organ that is responsible for nonshivering thermogenesis both in neonate and adult humans. Brown adipocytes possess an unparalleled ability to generate heat due to the dissociation of electron transport chain respiration from ATP production through uncoupling protein 1 (UCP1). Brown adipocyte mitochondria also display an elevated capacity for substrate utilization. A major source of substrate is the β-oxidation of long chain fatty acids (LCFA), which can be taken up from the circulation via fatty acid transport proteins (FATPs) or can be generated from endocytosed lipoproteins through a process mediated in part by the scavenger receptors. The scavenger receptor (SR) family of transmembrane glycoproteins mediates the binding and uptake of a broad range of ligands in a variety of tissues. A defining member of the SR-B receptors is CD36, which has been shown to be required in a variety of tissues for the uptake of several hydrophobic molecules, including LCFA and the carotenoid lycopene. More recently, it was demonstrated that CD36 is required for the endocytosis of lipoproteins by both macrophages and BAT.
The lipid coenzyme Q (CoQ; also known as ubiquinone) is an essential component of the mitochondrial electron transport chain. Low CoQ levels are associated with cardiomyopathies, aging, and statin-induced myopathies. There are also several genetic mutations directly affecting proteins involved in the synthesis of CoQ, resulting in primary CoQ deficiencies. Therefore, increasing CoQ levels could be therapeutically beneficial for a variety of metabolic diseases. Many tissues endogenously synthesize CoQ, and the contribution of dietary CoQ is thought to be comparatively small. However, exogenous uptake of CoQ from the circulation can be significant in situations where CoQ levels are already low, such as in genetic deficiencies, myopathies, and aging. Exactly how tissues take up CoQ and which tissues primarily depend on exogenous CoQ has not been well studied, posing a considerable challenge to the therapeutic use of CoQ in metabolic diseases, aging, and mitochondrial function. We have identified BAT as a major destination for exogenous CoQ, and that this uptake is dependent on CD36. We are currently examining the precise mechanism of CoQ uptake by CD36, the synthesis rate of CoQ in BAT lacking CD36, and the effect of exogenous CoQ on BAT function as a possible therapy for metabolic diseases.