Zabri_2026_Compr.Physiol_16_e70106

Adipose tissue ATGL has emerged as an important player in cardiovascular disease. Myocardial infarction is accompanied by sympathetic stimulation and activation of white adipose tissue and peripheral lipolysis. We therefore investigate here the role of adipocyte ATGL in a murine model of cardiac ischemia and reperfusion (I/R) by using an inducible, adipocyte specific KO of ATGL (iatATGL-KO). Notably this led to successfully inhibited lipolysis during cardiac ischemia, and KO mice exhibited aggravated cardiac dysfunction and enhanced scar formation after 28 days I/R. This phenotype went along with multiple structural and molecular alterations mainly in the subcutaneous white adipose tissue depot (iWAT) and brown adipose tissue (BAT). The iatATGL-KO mainly reduced BAT activation as well as adiponectin-secretion. In the heart spatial transcriptomic analysis suggested higher mechanical stress in the remote myocardium, which went along with higher oxygen consumption rates (OCR) and higher dependency on glucose as substrate after 24 h I/R. Taken together, iatATGL-KO hearts after I/R seem to be affected in multiple ways, such as a reduction in cardioprotective factors from iWAT and BAT as well as an oxygen wasting effect in the remote zone of the heart, which contribute to the worse outcome. This indicates a time and depot-specific role of adipocyte ATGL in cardiac ischemia and reperfusion injury.