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


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.
Kos
Katrina
K
Diabetes and Endocrinology Research Unit, Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK.
Wong
Steve
S
Tan
Bee
B
Gummesson
Anders
A
Jernas
Margareta
M
Franck
Niclas
N
Kerrigan
David
D
Nystrom
Fredrik H
FH
Carlsson
Lena M S
LM
Randeva
Harpal S
HS
Pinkney
Jonathan H
JH
Wilding
John P H
JP
D000273:Adipose Tissue / Q000502:physiology*; D000328:Adult; D050110:Bariatric Surgery; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology*; D004038:Diet, Reducing; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000097:blood*; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000235:genetics; D009765:Obesity / Q000097:blood* / Q000178:diet therapy / Q000503:physiopathology; D009767:Obesity, Morbid / Q000097:blood* / Q000503:physiopathology / Q000601:surgery; D015676:Osteonectin / Q000235:genetics* / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D015676:Osteonectin