Regulation of the Fibrosis and Angiogenesis Promoter SPARC/Osteonectin in Human Adipose Tissue by Weight Change, Leptin, Insulin, and Glucose

  1. Katrina Kos1,
  2. Steve Wong1,
  3. Bee Tan2,
  4. Anders Gummesson3,
  5. Margareta Jernas3,
  6. Niclas Franck4,
  7. David Kerrigan5,
  8. Fredrik H. Nystrom4,
  9. Lena M.S. Carlsson3,
  10. Harpal S. Randeva2,
  11. Jonathan H. Pinkney6 and
  12. John P.H. Wilding1
  1. 1Diabetes and Endocrinology Research Unit, Clinical Sciences Centre, University Hospital Aintree, Liverpool, U.K.;
  2. 2Endocrinology and Metabolism Group, Warwick Medical School, University of Warwick, U.K.;
  3. 3Department of Molecular and Clinical Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;
  4. 4Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Linköping University, Linköping, Sweden;
  5. 5Department of Surgery, University Hospital Aintree, Liverpool, U.K.;
  6. 6Unit of Diabetes, Peninsula Medical School, Truro, U.K.
  1. Corresponding author: John P.H. Wilding, j.p.h.wilding{at}liv.ac.uk.

Abstract

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.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received February 16, 2009.
    • Accepted April 26, 2009.
  • Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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  1. Diabetes vol. 58 no. 8 1780-1788
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