Glucocorticoids (GC) have potent actions upon human adipose tissue, promoting adipocyte differentiation, inhibiting preadipocyte proliferation and inducing lipolysis to generate free fatty acids (FFA) and glycerol through a putative action upon hormone sensitive lipase (HSL). FFA have been strongly implicated in the pathogenesis of insulin resistance, yet the molecular mechanisms that cause GC induced lipolysis are not clear. Recently, several novel lipases have been identified (ATGL/desnutrin, GS-2 and adiponutrin) although their role in human adipose tissue has not been fully elucidated. We have characterized the expression and GC regulation of these novel lipases in human subcutaneous (sc) and omental (om) adipose tissue and in a novel human sc cell line, chub-S7 cells.
Using real-time PCR, HSL, ATGL/desnutrin, GS-2 and adipnutrin were all expressed in sc and om adipose tissue (n=6). Expression of all lipases was similar in both depots, however, adiponutrin was most abundantly expressed. Relative levels of expression are shown in Table 1 (*P<0.05 vs. HSL expression)
In chub-s7 cells, differentiated in chemically defined media to obtain a mature adipocyte phenotype, expression of all novel lipases increased significantly across differentiation (ATGL/desnutrin 223.6 fold, GS-2 253.6 fold and adiponutrin 3080.6 fold, all P<0.05) In agreement with our whole tissue data, adiponutrin was more abundantly expressed than GS2 and Desnutrin. Dexamethasone treatment (1 uM, 24 hrs) failed to regulate mRNA expression of any novel lipase, however we observed a significant increase in glycerol release following Dex treatment (Ctrl 100% vs. Dex 176%±34% P<0.05).
In conclusion, all novel lipases are highly expressed in human adipose tissue and expression increases during adipocyte differentiation. In chub-S7 cells, GCs regulate lipolytic activity although do not regulate novel lipase mRNA expression. Further exploration of the role of these lipases and the impact of GC treatment in human adipose tissue is now warranted.