Differential expression of plasminogen activator inhibitor-1, tumor necrosis factor-alpha,TNF-alpha converting enzyme and ADAMTS family members in murine fat territories

Our objective was to investigate expression of A disintegrin and metalloproteinase (ADAM) and ADAM proteins with a thrombospondin (TS) motif (ADAMTS) family members in adipose tissue of lean and obese mice. Five-week-old male mice were kept on standard chow (SFD) or on high fat diet (HFD) for 15 weeks, and subcutaneous (SC) and gonadal (GON) adipose tissue, as well as mature adipocytes and stromal-vascular (S-V) cells were harvested. mRNA levels of plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-alpha (TNF-alpha), ADAM-17 (TACE or TNF-alpha converting enzyme), ADAMTS-1 and ADAMTS-8 were quantified in isolated adipose tissues and cell fractions, and during differentiation of murine preadipocytes. The HFD resulted in a significantly enhanced weight of isolated SC and GON fat pads, and in enhanced blood levels of glucose, cholesterol and PAI-1. ADAM-17, TNF-alpha, PAI-1, ADAMTS-1 and ADAMTS-8 mRNA were detected in both SC and GON adipose tissue of lean mice (SFD). In SC adipose tissue of obese mice (HFD), the expression of ADAM-17 and PAI-1 was enhanced and that of ADAMTS-1 reduced, whereas in GON adipose tissue expression of TNF-alpha was enhanced and that of ADAMTS-8 reduced. In lean and obese mice, expression of ADAM-17, ADAMTS-1 and ADAMTS-8 was higher in the S-V cell fraction than in mature adipocytes. During differentiation of murine 3T3-F442A preadipocytes, expression of ADAM-17 and ADAMTS-1 remained virtually unaltered, whereas that of ADAMTS-8 decreased as adipocytes matured. Several ADAM and ADAMTS family members are expressed in adipose tissue and during differentiation of preadipocytes. Modulation of their expression upon development of obesity is adipose tissue-dependent.