Figure 2.

Cartoon models of potential mechanisms underlying the altered adipocyte metabolism in HSL KO mice. Panel A. Since HSL is the key diacylglycerol lipase in adipose tissue, diacylglycerol accumulates in HSL null mice leading to the activation of protein kinase C family members and their downstream targets such as MAPK, thus affecting cell proliferation, apoptosis, and differentiation. Panel B. Since HSL is the key neutral cholesteryl ester hydrolase in adipose tissue, a regulatory pool of free cholesterol might be depleted in HSL null mice leading to an increase in the transcription factor SREBP2 (sterol regulatory element binding protein 2) and a subsequent up-regulation of its transcriptional targets such as UCP2 (uncoupling protein 2). Panel C. Since HSL mediates the mobilization of fatty acids, the release of specific fatty acids by HSL might be required for the production of ligands that are preferentially utilized by PPARγ. A relative lack of PPARγ ligands might suppress the mutual activation of PPARγ and C/EBPα, the 2 most important transcription factors required for adipocyte differentiation.