Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose
Kos, Katarina, Wong, Steve, Tan, Bee K., Gummesson, Anders, Jernas, Margareta, Franck, Niclas, Kerrigan, David, Nystrom, Fredrik H., Carlsson, Lena M. S., Randeva, Harpal S., Pinkney, Jonathan H. and Wilding, John P. H. (2009) Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose. In: 69th Annual Meeting of the American Diabetes Association, New Orleans, LA, June 05-09, 2009. Published in: Diabetes, Vol.58 (No.8). pp. 1780-1788.Full text not available from this repository.
Official URL: http://dx.doi.org/10.2337/db09-0211
OBJECTIVE-Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines.
RESEARCH DESIGN AND METHODS-Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ (450 kcal)/day for 16 weeks and serial subcutaneous-abdominal-adipose tissue (SCAT) biopsies (weight loss: 28 +/- 3.7 kg). Another six lean subjects underwent fast-food-based hyperalimentation for 4 weeks (weight gain: 7.2 +/- 1.6 kg). Finally, visceral adipose tissue explants were cultured with recombinant leptin, insulin, and glucose, and SPARC mRNA and protein expression determined by Western blot analyses.
RESULTS-SPARC expression in human adipose tissue correlated with fat mass and was higher in SCAT. Weight, loss induced by very-low-calorie diet lowered SPARC expression by 33% and increased by 30% in adipose tissue of subjects gaining weight after a fast-food diet. SPARC expression was correlated with leptin independent of fat mass and correlated with homeostasis model assessment-insulin resistance. In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein.
CONCLUSIONS-Our data suggest that SPARC Expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose. The profibrotic effects of SPARC may contribute to metabolic dysregulation in obesity. Diabetes 58:1780-1788, 2009
|Item Type:||Conference Item (Paper)|
|Subjects:||R Medicine > RC Internal medicine|
|Divisions:||Faculty of Medicine > Warwick Medical School > Translational & Systems Medicine > Metabolic and Vascular Health
Faculty of Medicine > Warwick Medical School
|Journal or Publication Title:||Diabetes|
|Publisher:||American Diabetes Association|
|Official Date:||August 2009|
|Number of Pages:||9|
|Page Range:||pp. 1780-1788|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Diabetes UK, Swedish Research Council, University Hospital of Linkoping Research Funds, Diabetes Research Centre of Linkoping University, Gamla Tjaenarinnor Foundation|
|Conference Paper Type:||Paper|
|Title of Event:||69th Annual Meeting of the American Diabetes Association|
|Type of Event:||Conference|
|Location of Event:||New Orleans, LA|
|Date(s) of Event:||June 05-09, 2009|
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