Figure 2.

ATGL-Mediated Lipolysis Is Required for PPAR Signaling and OXPHOS

Fatty acids from exogenous or endogenous sources are activated to acyl-CoAs, which are subject to mitochondrial oxidation or TG formation. ATGL-mediated lipolysis of TG generates lipolytic products (FA and DG), which may act directly (e.g., FA) or after conversion (e.g., DG to phospholipids) as ligands for nuclear receptors (for details see text). Activation of nuclear receptor PPARα via lipolytic cleavage of TGs is required for normal mitochondrial function and OXPHOS. In ATGL-deficient mice, defective PPARα activation and OXPHOS can be restored by treatment with PPARα agonists. ATGL, adipose triglyceride lipase; CD36, cluster of differentiation 36; DG, diacylglycerol; FA, fatty acid; FATP, fatty acid transport protein; LPL, lipoprotein lipase; OXPHOS, oxidative phosphorylation; PPARα/δ, peroxisome proliferator-activated receptor alpha/delta; RA, retinoic acid; RXR, retinoid X receptor; TG, triacylglycerol.