Title | Thrombospondin-1 is an adipokine associated with obesity, adipose inflammation, and insulin resistance. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Varma V, Yao-Borengasser A, Bodles AM, Rasouli N, Phanavanh B, Nolen GT, Kern EM, Nagarajan R, Spencer HJ, Lee M-J, Fried SK, McGehee RE, Peterson CA, Kern PA |
Journal | Diabetes |
Volume | 57 |
Issue | 2 |
Pagination | 432-9 |
Date Published | 2008 Feb |
ISSN | 1939-327X |
Keywords | Adipocytes, Adipose Tissue, Cell Culture Techniques, Cell Line, Gene Expression Regulation, Humans, Inflammation, Insulin Resistance, Macrophages, Obesity, Reference Values, RNA, Messenger, Stem Cells, Thrombospondin 1 |
Abstract | 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. RESEARCH DESIGN AND 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. |
DOI | 10.2337/db07-0840 |
Alternate Journal | Diabetes |
PubMed ID | 18057090 |
PubMed Central ID | PMC2877915 |
Grant List | R01 DK039176 / DK / NIDDK NIH HHS / United States R01 DK071346-01 / DK / NIDDK NIH HHS / United States R37 DK039176 / DK / NIDDK NIH HHS / United States R01 DK071346-02 / DK / NIDDK NIH HHS / United States R01 DK071349 / DK / NIDDK NIH HHS / United States R01 DK071346 / DK / NIDDK NIH HHS / United States DK 71346 / DK / NIDDK NIH HHS / United States DK 71349 / DK / NIDDK NIH HHS / United States R01 DK052398 / DK / NIDDK NIH HHS / United States R01 DK071346-04 / DK / NIDDK NIH HHS / United States DK 52398 / DK / NIDDK NIH HHS / United States DK 39176 / DK / NIDDK NIH HHS / United States DK 71277 / DK / NIDDK NIH HHS / United States R01 DK071277 / DK / NIDDK NIH HHS / United States R01 DK071346-03 / DK / NIDDK NIH HHS / United States UL1 TR001998 / TR / NCATS NIH HHS / United States M01 RR014288 / RR / NCRR NIH HHS / United States M01RR14288 / RR / NCRR NIH HHS / United States R01 HD034522-04 / HD / NICHD NIH HHS / United States |