Rosiglitazone reverses inflammation in epididymal white adipose tissue in hormone-sensitive lipase-knockout mice.

Hormone-sensitive lipase (HSL) plays a crucial role in intracellular lipolysis, and loss of HSL leads to diacylglycerol (DAG) accumulation, reduced fatty acid mobilization, and impaired peroxisome proliferator-activated receptor (PPAR) γ signaling. HSL knock-out mice exhibit adipose tissue inflammation, but the underlying mechanisms are still not clear. Here we investigated if and to what extent HSL loss contributes to endoplasmic reticulum (ER) stress and adipose tissue inflammation in HSL knock-out mice. Further, we were interested in how impaired PPARγ signaling affects the development of inflammation in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT) of HSL knock-out mice, and if DAG and ceramide (Cer) accumulation contribute to adipose tissue inflammation and ER stress. Ultrastructural analysis showed a markedly dilated ER in both eWAT and iWAT upon loss of HSL. In addition, HSL knock-out mice exhibited macrophage infiltration and increased F4/80 mRNA expression, a marker of macrophage activation, in eWAT, but not in iWAT. We show treatment with rosiglitazone, a PPARγ agonist, attenuated macrophage infiltration and ameliorated inflammation of eWAT, but expression of ER stress markers remained unchanged, as did DAG and Cer levels in eWAT. Taken together, we show HSL loss promoted ER stress in both eWAT and iWAT of HSL knock-out mice, but inflammation and macrophage infiltration occurred mainly in eWAT. Also, PPARγ activation reversed inflammation, but not ER stress and DAG accumulation. These data indicate that neither reduction of DAG levels nor ER stress contribute to the reversal of eWAT inflammation in HSL knock-out mice.