Differential Expression of Matrix Metalloproteinase 3 (MMP3) in Preadipocytes/Stromal Vascular Cells From Nonobese Nondiabetic Versus Obese Nondiabetic Pima Indians

• Published in: Diabetes (New York, N.Y.) Vol. 55; no. 11; pp. 3160 - 3165
• Main Authors: TRAURIG, Michael T, PERMANA, Paska A, NAIR, Saraswathy, KOBES, Sayuko, BOGARDUS, Clifton, BAIER, Leslie J
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-11-2006
• Subjects: Adipocytes - enzymology; Adult; Arizona; Biological and medical sciences; Blood Vessels - enzymology; Body fat; Body Mass Index; Butter; Care and treatment; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 11; Diabetes; Diabetes mellitus; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Genetic aspects; Genetic Variation; Humans; Indians, North American - genetics; Male; Matrix Metalloproteinase 3 - genetics; Matrix metalloproteinase inhibitors; Medical sciences; Metabolic diseases; Obesity; Obesity - genetics; Polymerase Chain Reaction; Risk factors; Sex Characteristics; Stromal Cells - enzymology; Thinness - genetics; Arizona; United States > US; Endocrinopathy; Peptidases; Obesity; Stromelysin 1; Enzyme; Diabetes mellitus; Nutrition disorder; Hydrolases; Metalloendopeptidases; Indian; Preadipocyte; Nutritional status
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db06-0373

Differential Expression of Matrix Metalloproteinase 3 ( MMP3 ) in Preadipocytes/Stromal Vascular Cells From Nonobese Nondiabetic Versus Obese Nondiabetic Pima Indians
Michael T. Traurig ,
Paska A. Permana ,
Saraswathy Nair ,
Sayuko Kobes ,
Clifton Bogardus and
Leslie J. Baier
From the Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes
and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona
Address correspondence and reprint requests to Leslie J. Baier, PhD, NIDDK, NIH, 445 North 5th St., Phoenix, AZ 85004. E-mail:
lbaier{at}phx.niddk.nih.gov
Abstract
Prior microarray studies comparing global gene expression patterns in preadipocytes/stromal vascular cells isolated from nonobese
nondiabetic versus obese nondiabetic Pima Indians showed that matrix metalloproteinase 9 ( MMP9 ) is upregulated in obese subjects. The current study targeted analysis of nine additional MMP genes that cluster to a region on chromosome 11q22 that is linked to BMI and percent body fat. Differential-display PCR showed
that MMP3 is downregulated in preadipocytes/stromal vascular cells from obese subjects, and real-time PCR showed that MMP3 expression levels are negatively correlated with percent body fat. To determine whether variants within MMP3 are responsible for its altered expression, MMP3 was sequenced, and seven representative variants were genotyped in 1,037 Pima subjects for association analyses. Two variants
were associated with both BMI and type 2 diabetes, and two additional variants were associated with type 2 diabetes alone;
however, none of these variants were associated with MMP3 expression levels. We propose that the MMP3 pathway is altered in human obesity, but this alteration may be the result of a combination of genetic variation within the
MMP3 locus itself, as well as variation in additional factors, either primary or secondary to obesity, that regulate expression
of the MMP3 gene.
GAPDH, glyceraldehyde-3-phosphate dehydrogenase
MMP, matrix metalloproteinase
SNP, single nucleotide polymorphism
UTR, untranslated region
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.
Accepted July 31, 2006.
Received March 21, 2006.
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