Novel Communication Between Myocyte Lipid Storage and Fat Burning Unveiled

Abstract

### ATGL-Mediated Fat Catabolism Regulates Mitochondrial Function Via PPAR-α and PGC-1 Haemmerle et al Nature . 2011:17:1076–1085. A recent study unveils a fascinating role for an intracellular lipase in cardiac myocytes. The new results demonstrate that liberation of lipid species from myocyte neutral lipid stores results in activation of the nuclear receptor peroxisome proliferator-activated receptor α (PPARα) and the transcriptional coactivators, PPARγ coactivator 1 (PGC-1) α and β, chief regulators of cardiac mitochondrial fat burning capacity. Deficiency of this lipase in mice causes a cardiomyopathy with myocyte lipid accumulation and mitochondrial dysfunction. The adult mammalian heart burns enormous quantities of fatty acids (FA) to meet its high energy demand. FA import, storage, and oxidation must be tightly coordinated to maintain cardiac myocyte lipid balance while yielding sufficient fuel supply. Significant progress has been made in the delineation of gene regulatory networks involved in the coordinate control of myocyte FA uptake and oxidation. The PPARs, which belong to a family of nuclear receptor transcription factors,1 have been shown to regulate the expression of almost every protein and enzyme involved in cellular FA import and oxidation pathways, the latter taking place in the mitochondria, and to a lesser extent in peroxisomes. The PPARs are activated by endogenous lipid ligands, the identity of which remains unknown in the myocyte. However, little is known about the regulatory mechanisms that link myocyte lipid storage with downstream pathways involved in FA catabolism. A recent study by Haemmerle et al2 sheds light on how the myocyte neutral lipid storage depot communicates with downstream FA utilization pathways. The results of this study suggest that in contrast to the commonly held dogma, myocyte lipid storage is not simply an inert reservoir but actually serves to instruct downstream FA oxidation pathways within the mitochondrion. Previously, this group found that mice lacking adipose triglyceride lipase (ATGL) develop a cardiomyopathy characterized by dramatic myocyte lipid accumulation.3 …