Expression of aggrecan(ases) during murine preadipocyte differentiation and adipose tissue development.
The expression and potential functional role of aggrecan in adipogenesis and adipose tissue development was investigated in murine models of obesity. Aggrecan, as well as the two aggrecanases ADAMTS-4 and ADAMTS-5 (A Disintegrin And Metalloproteinase with Thrombospondin motif) mRNAs, are expressed in subcutaneous (SC) and gonadal (GON) adipose tissues of mice. Their presence was confirmed by western blotting using adipose tissue extracts. In mice with nutritionally induced obesity (high fat diet) as well as in lean controls, aggrecan mRNA expression was downregulated whereas ADAMTS-4 and ADAMTS-5 were upregulated with time. In mice with genetically determined obesity (ob/ob), ADAMTS-5 mRNA was upregulated in both SC and GON adipose tissues, as compared to wild-type (WT) mice (p<0.001). Enhanced aggrecanase expression levels in these tissues were associated with significantly elevated levels of G1-NITEGE, a degradation product of aggrecan. Thus, aggrecan levels were high at the early stages of adipose tissue development in mice, whereas its production decreased and its degradation increased during development of obesity. A functional role of aggrecan in promoting early stages of adipogenesis is supported by the findings that it stimulated the in vitro differentiation of 3T3-F442A preadipocytes and the de novo in vivo accumulation of fat in Matrigel plaques injected into WT mice. Proteoglycans in the extracellular matrix of adipose tissue, such as aggrecan, may contribute to the regulation of lipid uptake and obesity in mice.
Voros
Gabor
G
Center for Molecular and Vascular Biology, KU Leuven, Campus Gasthuisberg, O&N, Herestraat 49, Leuven, Belgium.
Sandy
John D
JD
Collen
Désiré
D
Lijnen
H Roger
HR
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D000273:Adipose Tissue / Q000166:cytology / Q000254:growth & development*; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D017931:DNA Primers; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011348:Procollagen N-Endopeptidase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053674:Aggrecans; D017931:DNA Primers; D012333:RNA, Messenger; D010450:Endopeptidases; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C498489:Adamts5 protein, mouse; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603919:Adamts4 protein, mouse; C083641:aggrecanase