Dependence of Brown Adipose Tissue Function on CD36-Mediated Coenzyme Q Uptake

Abstract

Summary Brown adipose tissue (BAT) possesses the inherent ability to dissipate metabolic energy as heat through uncoupled mitochondrial respiration. An essential component of the mitochondrial electron transport chain is coenzyme Q (CoQ). While cells mostly synthesize CoQ endogenously, exogenous supplementation with CoQ has been successful as a therapy for patients with CoQ deficiency. However, which tissues depend on exogenous CoQ uptake as well as the mechanism by which CoQ is taken up by cells and the role of this process in BAT function is not well understood. Here we report that the scavenger receptor CD36 drives the uptake of CoQ by BAT and is required for normal BAT function. BAT from mice lacking CD36 displays CoQ deficiency, impaired CoQ uptake, hypertrophy, altered lipid metabolism, mitochondrial dysfunction, and defective non-shivering thermogenesis. Together, these data reveal an important new role for the systemic transport of CoQ to BAT and its function in thermogenesis.

Impaired thermogenesis and sharp increases in plasma triglyceride levels in GPIHBP1-deficient mice during cold exposure

“…A deficiency of CD36, a putative fatty acid transporter, also leads to cold intolerance (13,14). In the current study, we had hoped to determine whether a combined deficiency of GPIHBP1 and CD36 would cause an exaggerated cold intolerance phenotype.…”

“…For example, a deficiency in fatty acid binding protein 3 (FABP3) or a combined deficiency of FABP4 and FABP5 impairs fatty acid oxidation in brown adipose tissue (BAT), leading to cold intolerance (11,12). A deficiency of CD36, a putative fatty acid transporter, also causes cold intolerance (13,14).…”

Resveratrol and para-coumarate serve as ring precursors for coenzyme Q biosynthesis

“…3C ). These results suggest that although pABA is prenylated and can be further modifi ed by UbiD, UbiX, and UbiI, E. coli may not be able to process the aniline-containing ring intermediates to later intermediates or to Q 8 .…”

“…Additional ring modifi cations catalyzed by UbiH, UbiE, UbiF, and UbiG form the fi nal product Q 8 H 2 . UbiB and UbiJ are required for Q 8 biosynthesis, but their function is yet to be determined. Boxed compounds designate the aromatic ring precursors tested in this study.…”

“…UbiI adds the fi rst hydroxyl group at the C5 position, followed by O-methylation catalyzed by UbiG, the homolog of yeast Coq3. Additional ring modifi cations catalyzed by UbiH, UbiE, UbiF, and UbiG generate the fi nal product of Q 8 . UbiB, an atypical protein kinase similar animal cells (15)(16)(17).…”