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

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. Diabetes 55: 3160 -3165, 2006

Macrophages regulate tumor necrosis factor-α expression in adipocytes through the secretion of matrix metalloproteinase-3

“…A recent study reported that the MMP-3 expression levels are negatively correlated with percent body fat, and the MMP-3 gene variants are associated with both BMI and type 2 diabetes in Pima Indians. 28 The mice with transplanted cultured 3T3-L1 cells showed that the transplanted adipocytes in the visceral space, and Macrophage MMP-3 for the function of adipocytes H Unoki et al not subcutaneous space, increased TNF-a gene expression. 5 A microarray analysis revealed that the MMP-3 gene expression is drastically induced in addition to TNF-a.…”

Applying Novel Genome-Wide Linkage Strategies to Search for Loci Influencing Type 2 Diabetes and Adult Height in American Samoa

“…The largest two-dimensional MLS for the stringent phenotype was detected in region 11q22, which previously has been implicated as conferring susceptibility to T2DM (Traurig et al 2006) and T1DM (Dong et al 2007), and in region 21q21, which has been suggested as a potential locus for T1DM (Bergholdt et al 2005). Similarly, the largest two-dimensional MLS for the broad phenotype was detected on chromosomes 12q24 and 20q13.…”

“…Chromosome 4p15 has been suggested as a susceptibility region for T2DM (Wiltshire et al 2004), and 7q31 has been suggested to carry a susceptibility locus for metabolic syndrome (Loos et al 2003) and for fasting insulin levels (Lakka et al 2003). The largest two-dimensional MLS for the stringent phenotype was detected in region 11q22, which previously has been implicated as conferring susceptibility to T2DM (Traurig et al 2006) and T1DM (Dong et al 2007), and in region 21q21, which has been suggested as a potential locus for T1DM (Bergholdt et al 2005). Similarly, the largest two-dimensional MLS for the broad phenotype was detected on chromosomes 12q24 and 20q13.…”

Polymorphisms of matrix metalloproteinase gene and adiposity indices in European children: results of the IDEFICS study

“…A candidate gene study on the role of MMP3 gene variants in obesity was published in a population of adult Pima Indians, 18 while no study has yet been performed in adult Caucasians or in children. The authors reported that variants rs650108 and rs522616 of MMP3 gene were associated with both BMI and type 2 diabetes under a dominant model.…”

“…16,17 Experimental studies demonstrated that mouse MMP3 is involved in adipose tissue formation and that changes in its expression could be related to obesity-mediated adipose tissue remodeling. 12 Moreover, a study conducted in Pima Indians 18 showed that MMP3 gene was expressed in preadipocytes/stromal vascular cells and its expression was associated with variations in body fat. Therefore, we investigated the association of MMP3 gene polymorphisms with BMI and other indices of adiposity, not yet investigated in Caucasian adults or in children, in the largest prospective European cohort of children established to date, participating in the Identification and Prevention of Dietary-and Lifestyle-Induced Health Effects in Children and Infants (IDEFICS) project.…”