Differential transcriptional modulation of biological processes in adipocyte triglyceride lipase and hormone-sensitive lipase-deficient mice.
Adipocyte triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are intracellular lipases that mobilize triglycerides, the main energy source in mammals. Deletion of genes encoding ATGL (Pnpla2) or HSL (Lipe) in mice results in striking phenotypic differences, suggesting distinct roles for these lipases. The goal of the present study was to identify the biological processes that are modulated in the metabolic tissues of ATGL- and HSL-deficient mice. DNA microarrays were employed to provide full genome coverage concerning the types of genes that are differentially expressed in wild-type and mutant mice. For both mouse models, transcript signatures were identified in white adipose tissue, brown adipose tissue (BAT), skeletal muscle (SM), cardiac muscle (CM), and liver. Genetic ablation of ATGL and HSL alters the transcript levels of a large number of genes in metabolic tissues. The genes affected in the two models are, however, largely different ones. Indeed, only one biological process was modulated in the same way in both mouse models, namely the down-regulation of fatty acid metabolism in BAT. The most pronounced modulation of biological processes was observed in ATGL-/- CM, in which a concerted down-regulation of transcripts associated with oxidative pathways was observed. In HSL-/- mice, in contrast, the most marked changes were seen in SM, namely, alterations in transcript levels reflecting a change of energy source from lipid to carbohydrate. The transcript signatures also provided novel insights into the metabolic derangements that are characteristic of ATGL-/- mice. Our findings suggest that ATGL and HSL differentially modulate biological processes in metabolic tissues. We hypothesize that the intermediary metabolites of the lipolytic pathways are signaling molecules and activators of a wide range of biochemical and cellular processes in mammals.
Pinent
Montserrat
M
Institute for Genomics and Bioinformatics, Graz University of Technology, 8010 Graz, Austria.
Hackl
Hubert
H
Burkard
Thomas Rainer
TR
Prokesch
Andreas
A
Papak
Christine
C
Scheideler
Marcel
M
Hämmerle
Günter
G
Zechner
Rudolf
R
Trajanoski
Zlatko
Z
Strauss
Juliane Gertrude
JG
D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000235:genetics*; D015536:Down-Regulation; D004734:Energy Metabolism / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D008049:Lipase; D050356:Lipid Metabolism / Q000235:genetics*; D008066:Lipolysis / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D002787:Sterol Esterase / Q000235:genetics*; D022722:Thermogenesis / Q000235:genetics; D014018:Tissue Distribution; D014158:Transcription, Genetic; D000217:Acyltransferases
D002265:Carboxylic Ester Hydrolases; D008049:Lipase; D002787:Sterol Esterase; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases