Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members

Abstract

Adiponutrin and a related protein, adipocyte triglyceride lipase (ATGL; also known as Desnutrin), were recently described as adipocyte-specific proteins with lipid hydrolase activity. Using bioinformatics, we identified three additional Adiponutrin family members (GS2, GS2-Like, and PNPLA1). Here, we report on the expression, regulation, and activity of GS2 and GS2-Like compared with Adiponutrin and Desnutrin/ATGL. GS2-Like is expressed and regulated in a manner similar to Adiponutrin; however, the absolute levels of mRNA are significantly lower than those of Adiponutrin or Desnutrin/ATGL. GS2 transcripts were identified only in humans and are highly expressed in adipose as well as other tissues. All four proteins show lipase activity in vitro, which is dependent on the presence of the active site serine for Adiponutrin, Desnutrin/ATGL, and GS2. Overexpression of Desnutrin/ATGL, GS2, and GS2-Like, but not Adiponutrin, decreases intracellular triglyceride levels. This is consistent with a function for Desnutrin/ATGL, GS2, and GS2-Like in lipolysis, but not for Adiponutrin. Consistent with previously reported data, Desnutrin/ATGL is upregulated by fasting in adipose tissue, whereas Adiponutrin is downregulated. Additionally, Adiponutrin and GS2-Like, but not Desnutrin/ATGL, are strongly induced in the liver of ob/ob mice.Our data support distinct functions for Adiponutrin and Desnutrin/ATGL and raise the possibility that GS2 may contribute significantly to lipolysis in human adipose tissue.

PPARγ agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control

“…A fairly robust correlation was found between basal rates of release of lipolytic products and mRNA levels of ATGL. This correlation obviously does not establish a cause and effect relationship; however, the importance of the expression level of ATGL in WAT lipolysis is highlighted by recent studies in which ATGL overexpression in 3T3-L1 adipocytes enhanced both fasting basal and isoproterenolstimulated lipolysis, whereas the opposite effects were found with inhibition of ATGL through antisense technology [12,16,27]. The functional importance of lipase .…”

PNPLA3 gene in liver diseases

“…PNPLA3 exhibits predominantly hydrolase (lipase) activity in vitro against triglycerides (TG) and retinyl esters in hepatic stellate cells [76,[78][79][80] (Fig. 1).…”

Les protéines à domaine patatine

“…Aucune information sur la relevance fonctionnelle physiologique de PNPLA1 n'a pu être apportée jusqu'à présent, l'expression du gène étant extrêmement faible dans tous les tissus testés [28,29]. Cette observation est renforcée par le très faible nombre d'EST (expressed sequence tag) trouvé dans les banques de séquences.…”

“…Le gène codant pour GS2 (PNPLA4) est absent chez la souris mais présent chez l'homme et le rat. Il est fortement exprimé dans nombre de tissus actifs sur le plan métabolique comme le tissu adipeux, le muscle cardiaque, le foie et la peau [28,29]. Des travaux menés sur les kératinocytes humains ont permis la mise en évi-dence des activités rétinol lipase et transacylase susceptibles de participer à la morphogenèse de l'épiderme [30].…”

“…Le gène GS2-like (codant PNPLA5) est localisé à proximité du gène de l'adiponutrine suggérant une duplication ancestrale. Bien que faible, son expression est néanmoins détectée dans de nombreux tissus comme les poumons, les tissus adipeux et le cerveau [28,29]. Induite au cours de la différenciation adipocytaire chez la souris, cette expression est très sensible à l'état nutritionnel : dans le tissu adipeux, la prise alimentaire la stimule et le jeûne la réprime.…”