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Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose.

Kos K, Wong S, Tan B, Gummesson A, Jernas M, Franck N, Kerrigan D, Nystrom FH, Carlsson LM, Randeva HS, Pinkney JH, Wilding JP - Diabetes (2009)

Bottom Line: Adipose tissue collagen has recently been found to be linked with metabolic dysregulation.In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein.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.

View Article: PubMed Central - PubMed

Affiliation: Diabetes and Endocrinology Research Unit, Clinical Sciences Centre, University Hospital Aintree, Liverpool, 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.

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Related in: MedlinePlus

SPARC and relation to fat mass, HOMA-IR, and adipokine expression. A: Depot expression of SPARC and its correlation with fat mass. B: VAT and SCAT-SPARC expression and HOMA-IR. C: VAT expression of adiponectin and SPARC. D: The correlation of SPARC expression with leptin. Values are expressed in signal units.
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Figure 2: SPARC and relation to fat mass, HOMA-IR, and adipokine expression. A: Depot expression of SPARC and its correlation with fat mass. B: VAT and SCAT-SPARC expression and HOMA-IR. C: VAT expression of adiponectin and SPARC. D: The correlation of SPARC expression with leptin. Values are expressed in signal units.

Mentions: We did not find a sex difference in expression of BMI-matched men and women. Both SCAT- and VAT-derived SPARC showed a positive correlation with fat mass (Fig. 2) and with waist circumference (Table 4) in the depot study. SPARC was strongly correlated with high-sensitivity C-reactive protein but not with circulating tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6). SPARC was correlated with local adipose tissue expression of the macrophage-migration inhibitory factor (MMIF; r = 0.3, P < 0.05), but only SCAT expression of SPARC correlated with local IL-6 expression (r = −0.3, P < 0.05). TNF-α, macrophage inflammatory protein-1 (MIP-1), monocyte chemoattractant protein-1 (MCP-1), or regulated upon activation normal T-cell expressed and secreted expression showed no association with SPARC expression (Table 4).


Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose.

Kos K, Wong S, Tan B, Gummesson A, Jernas M, Franck N, Kerrigan D, Nystrom FH, Carlsson LM, Randeva HS, Pinkney JH, Wilding JP - Diabetes (2009)

SPARC and relation to fat mass, HOMA-IR, and adipokine expression. A: Depot expression of SPARC and its correlation with fat mass. B: VAT and SCAT-SPARC expression and HOMA-IR. C: VAT expression of adiponectin and SPARC. D: The correlation of SPARC expression with leptin. Values are expressed in signal units.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2712789&req=5

Figure 2: SPARC and relation to fat mass, HOMA-IR, and adipokine expression. A: Depot expression of SPARC and its correlation with fat mass. B: VAT and SCAT-SPARC expression and HOMA-IR. C: VAT expression of adiponectin and SPARC. D: The correlation of SPARC expression with leptin. Values are expressed in signal units.
Mentions: We did not find a sex difference in expression of BMI-matched men and women. Both SCAT- and VAT-derived SPARC showed a positive correlation with fat mass (Fig. 2) and with waist circumference (Table 4) in the depot study. SPARC was strongly correlated with high-sensitivity C-reactive protein but not with circulating tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6). SPARC was correlated with local adipose tissue expression of the macrophage-migration inhibitory factor (MMIF; r = 0.3, P < 0.05), but only SCAT expression of SPARC correlated with local IL-6 expression (r = −0.3, P < 0.05). TNF-α, macrophage inflammatory protein-1 (MIP-1), monocyte chemoattractant protein-1 (MCP-1), or regulated upon activation normal T-cell expressed and secreted expression showed no association with SPARC expression (Table 4).

Bottom Line: Adipose tissue collagen has recently been found to be linked with metabolic dysregulation.In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein.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.

View Article: PubMed Central - PubMed

Affiliation: Diabetes and Endocrinology Research Unit, Clinical Sciences Centre, University Hospital Aintree, Liverpool, 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.

Show MeSH
Related in: MedlinePlus