PVAT encompassing thoracic aortas of wild-type (WT) and ATGL(−/−) mice was isolated, characterized, and analyzed for protein and mRNA expression of different adipokines, inflammation markers, and sources of oxidative stress using real-time PCR and Western blot analysis, respectively. Knockout of ATGL caused a 7-fold increase in PVAT wet weight. While mRNA expression of adiponectin was reduced to about 50%, leptin mRNA was increased about 4-fold in ATGL deficiency. Adipose mRNA levels of the inflammation markers tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6) were about 5-fold higher in ATGL-deficient PVAT. In addition, the NOX2/p67phox complex was significantly upregulated at protein level. Heme oxygenase-1, which has been described protective against oxidative and inflammatory stress, was increased about 5-fold in ATGL deficiency. To distinguish between direct PVAT-mediated effects and those originating from the cardiac dysfunctional phenotype of the animals, we additionally analyzed tissue isolated from ATGL(−/−) mice with cardiomyocyte-specific overexpression of ATGL (rescued cardiac phenotype). Interestingly, the effect of ATGL knockout on TNF-α and leptin expression was reversible. By contrast, increased adipose NOX2/p67phox, MCP-1 and IL-6 expression persisted even upon restoration of cardiac function.