Thrombospondin-1 is an adipokine associated with obesity, adipose inflammation, and insulin resistance.
OBJECTIVE
We examined the relationship between the expression of thrombospondin (TSP)1, an antiangiogenic factor and regulator of transforming growth factor-beta activity, obesity, adipose inflammation, and insulin resistance.


METHODS
TSP1 gene expression was quantified in subcutaneous adipose tissue (SAT) of 86 nondiabetic subjects covering a wide range of BMI and insulin sensitivity, from visceral adipose (VAT) and SAT from 14 surgical patients and from 38 subjects with impaired glucose tolerance randomized to receive either pioglitazone or metformin for 10 weeks. An adipocyte culture system was also used to assess the effects of pioglitazone and coculture with macrophages on TSP1 gene expression.


RESULTS
TSP1 mRNA was significantly associated with obesity (BMI) and insulin resistance (low insulin sensitivity index). Relatively strong positive associations were seen with markers of inflammation, including CD68, macrophage chemoattractant protein-1, and plasminogen activator inhibitor (PAI)-1 mRNA (r >/= 0.46, P = 0.001 for each), that remained significant after controlling for BMI and S(i). However, TSP1 mRNA was preferentially expressed in adipocyte fraction, whereas inflammatory markers predominated in stromal vascular fraction. Coculture of adipocytes and macrophages augmented TSP1 gene expression and secretion from both cell types. Pioglitazone (not metformin) treatment resulted in a 54% decrease (P < 0.04) in adipose TSP gene expression, as did in vitro pioglitazone treatment of adipocytes.


CONCLUSIONS
TSP1 is a true adipokine that is highly expressed in obese, insulin-resistant subjects; is highly correlated with adipose inflammation; and is decreased by pioglitazone. TSP1 is an important link between adipocytes and macrophage-driven adipose tissue inflammation and may mediate the elevation of PAI-1 that promotes a prothrombotic state.
Varma
Vijayalakshmi
V
Central Arkansas Veterans Healthcare System, 598/151 LR, 4300 West 7th St., Little Rock, AR 72205, USA.
Yao-Borengasser
Aiwei
A
Bodles
Angela M
AM
Rasouli
Neda
N
Phanavanh
Bounleut
B
Nolen
Greg T
GT
Kern
Emily M
EM
Nagarajan
Radhakrishnan
R
Spencer
Horace J
HJ
Lee
Mi-Jeong
MJ
Fried
Susan K
SK
McGehee
Robert E
RE
Peterson
Charlotte A
CA
Kern
Philip A
PA
D017667:Adipocytes / Q000502:physiology; D000273:Adipose Tissue / Q000502:physiology; D018929:Cell Culture Techniques; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007333:Insulin Resistance; D008264:Macrophages / Q000502:physiology; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D019700:Thrombospondin 1 / Q000235:genetics*
D012333:RNA, Messenger; D019700:Thrombospondin 1