Supplemental Table 1. Uniquely up- and down- regulated in the inguinal fat pads of wild-type ( MMP14 +/++/++/+ ) in response to nutritional change (HFD versus CD) Up-regulated genes HFD/CD (log2 Probe Symbol Description HFD 1 HFD 2 CD 1 CD 2 scale) 1434679_at Ncan neurocan 2.86 7.72 7.92 4.84 5.09 1422155_at Hist2h3c2 histone cluster 2, H3c2 2.08 8.53 8.53 6.41 6.50 1417688_at Fam20c family with sequence similarity 20, member C 2.02 9.45 9.37 7.39 7.39 1447520_at Lbp lipopolysaccharide binding 2.44 8.28 8.17 5.65 5.93 1452243_at Kcnj14 potassium inwardly-rectifying channel, subfamily J, member 14 1.87 7.48 7.56 5.61 5.69 1420674_at Pla2g2e phospholipase A2, group IIE 1.90 7.71 7.91 5.92 5.89 1417903_at Dfna5 deafness, autosomal dominant 5 () 1.73 6.90 7.01 5.23 5.22 1423294_at Mest mesoderm specific transcript 3.86 11.47 12.03 7.62 8.16 1424338_at Slc6a13 solute carrier family 6 (neurotransmitter transporter, GABA), member 13 1.67 8.97 9.03 7.29 7.36 1436829_at Trim67 tripartite motif-containing 67 2.07 7.95 8.27 6.01 6.07 1422561_at Adamts5 a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 5 (aggrecanase-2) 1.50 11.82 11.89 10.34 10.37 1422655_at Ptch2 patched homolog 2 1.55 7.91 8.09 6.45 6.45 1455099_at Mogat2 monoacylglycerol O-acyltransferase 2 1.53 6.75 6.54 5.12 5.10 1420553_x_at Serpina1a (or cysteine) peptidase inhibitor, clade A, member 1A 2.13 6.24 6.29 3.91 4.36 1455447_at D430019H16Rik RIKEN cDNA D430019H16 1.88 9.74 9.73 7.68 8.04 1423516_a_at Nid2 nidogen 2 1.34 9.17 9.21 7.80 7.90 1423693_at Ela1 elastase 1, pancreatic 1.40 9.11 9.24 7.72 7.84 1435314_at Tph2 2 2.19 5.54 6.04 3.51 3.69 1425891_a_at Grtp1 GH regulated TBC protein 1 1.28 7.93 7.86 6.59 6.65 1428005_at Mosc1 MOCO sulphurase C-terminal domain containing 1 2.48 9.21 9.55 6.64 7.16 1452646_at Trp53inp2 transformation related protein 53 inducible nuclear protein 2 1.54 12.95 13.07 11.59 11.35 1434129_s_at Lhfpl2 lipoma HMGIC fusion partner-like 2 1.29 10.41 10.39 9.05 9.18 1435950_at Hr hairless 1.48 8.49 8.42 6.85 7.10 1416321_s_at Prelp proline arginine-rich end leucine-rich repeat 1.46 11.92 11.96 10.60 10.36 1449152_at Cdkn2b cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) 1.25 8.03 8.04 6.84 6.73 1434342_at S100b , beta polypeptide, neural 1.70 8.50 8.38 6.92 6.57 1426562_a_at Olfm1 olfactomedin 1 1.80 8.37 8.31 6.34 6.75 1423136_at Fgf1 fibroblast growth factor 1 1.49 8.48 8.49 6.85 7.14 1445546_at AI844685 expressed sequence AI844685 1.42 9.70 9.93 8.35 8.45 1440649_at EG232599 predicted gene, EG232599 1.33 6.35 6.55 5.08 5.17 1425227_a_at Atp6v0a1 ATPase, H+ transporting, lysosomal V0 subunit A1 1.13 7.07 7.10 5.95 5.97 1434051_s_at Hspa12a heat shock protein 12A 1.36 9.31 9.38 7.86 8.11 1420655_at Pnpla3 patatin-like phospholipase domain containing 3 1.77 11.49 11.47 9.95 9.48 1429030_at C1qtnf7 C1q and tumor necrosis factor related protein 7 1.36 6.94 6.89 5.41 5.69 1416953_at Ctgf connective tissue growth factor 1.25 8.84 8.68 7.59 7.43 1425385_a_at Igh-6 immunoglobulin heavy chain 6 (heavy chain of IgM) 2.45 12.19 12.62 9.65 10.26 1426913_at Lss lanosterol synthase 1.61 7.13 7.12 5.30 5.72 1416121_at Lox lysyl oxidase 1.21 10.97 11.17 9.90 9.81 1416455_a_at Cryab crystallin, alpha B 1.13 10.55 10.71 9.52 9.48 1422558_at Gamt guanidinoacetate methyltransferase 1.15 8.71 8.68 7.45 7.64 1453592_at Lrrc39 leucine rich repeat containing 39 1.13 7.47 7.66 6.42 6.45 1416311_s_at Tuba3a , alpha 3A 1.10 7.83 7.69 6.62 6.71 1417673_at Grb14 growth factor receptor bound protein 14 2.27 10.51 10.38 7.81 8.53 1450344_a_at Ptger3 prostaglandin E receptor 3 (subtype EP3) 1.32 11.28 11.43 10.17 9.89 1422878_at Syt12 XII 1.02 9.51 9.61 8.53 8.53 1422580_at Myl4 , light polypeptide 4 1.45 8.72 8.58 7.01 7.39 1439849_at OTTMUSG00000008561 predicted gene, OTTMUSG00000008561 1.03 8.42 8.55 7.43 7.48 1433443_a_at LOC100040592 similar to Hmgcs1 protein 1.05 12.29 12.35 11.20 11.33 1434188_at Slc16a12 solute carrier family 16 (monocarboxylic acid transporters), member 12 1.50 9.01 9.18 7.39 7.78 1422582_at Lep leptin 2.38 12.60 12.58 9.81 10.61 1418884_x_at Tuba1a tubulin, alpha 1A 1.09 13.64 13.55 12.43 12.59 1450702_at Hfe hemochromatosis 1.03 9.09 9.12 8.00 8.15 1420944_at Zfp185 finger protein 185 1.08 8.41 8.46 7.26 7.45 1423179_at Kcnb1 potassium voltage gated channel, Shab-related subfamily, member 1 1.22 7.11 7.19 6.07 5.79 1460583_at Golt1b golgi transport 1 homolog B (S. cerevisiae) 1.04 7.01 6.91 5.85 5.99 1450286_at Npr3 natriuretic peptide receptor 3 2.72 9.16 9.65 6.26 7.10 1455299_at Vgll3 vestigial like 3 (Drosophila) 1.70 8.35 8.69 6.61 7.03 1440888_at Oxtr oxytocin receptor 1.65 7.85 8.02 6.04 6.53 1423369_at Fmr1 fragile X mental retardation syndrome 1 homolog 1.33 11.45 11.52 9.98 10.33 1455025_at Paqr9 progestin and adipoQ receptor family member IX 1.26 10.20 10.22 9.11 8.78 1416529_at Emp1 epithelial 1 1.70 12.48 12.45 10.49 11.04 1427247_at D3Bwg0562e DNA segment, Chr 3, Brigham & Women's Genetics 0562 expressed 1.33 6.77 6.83 5.29 5.66 1427123_s_at Copg2as2 coatomer protein complex, subunit gamma 2, antisense 2 1.06 7.44 7.31 6.23 6.39 1455720_at Adamts2 a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 2 1.44 6.89 7.17 5.75 5.41 1426513_at Rbm28 RNA binding motif protein 28 1.12 9.11 9.18 7.89 8.16 1427299_at Rps6ka3 ribosomal protein S6 kinase polypeptide 3 1.03 8.88 8.94 7.77 7.98 1434520_at Sc5d sterol-C5-desaturase (fungal ERG3, delta-5-desaturase) homolog (S. cerevisae) 1.21 9.93 10.12 8.95 8.67 1427352_at Krt79 79 1.02 8.00 7.97 7.07 6.86 1418123_at Unc119 unc-119 homolog (C. elegans) 1.01 9.61 9.74 8.57 8.74 1429135_at 1110059M19Rik RIKEN cDNA 1110059M19 gene 2.74 8.72 8.98 5.59 6.63 1438756_at Ankrd29 repeat domain 29 1.54 7.54 7.71 5.82 6.34 1425039_at Itgbl1 , beta-like 1 1.15 7.79 7.62 6.41 6.69 1436200_at Lonrf3 LON peptidase N-terminal domain and ring finger 3 1.18 6.39 6.35 5.36 5.02 1436359_at Ret ret proto-oncogene 1.54 7.50 7.74 5.82 6.32 1420427_a_at Dhx32 DEAH (Asp-Glu-Ala-His) box polypeptide 32 1.16 9.26 9.58 8.32 8.21 1429183_at Pkp2 2 1.39 8.56 8.84 7.11 7.51 1428738_a_at D14Ertd449e DNA segment, Chr 14, ERATO Doi 449, expressed 1.04 10.48 10.72 9.63 9.50

©2010 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/cgi/content/full/db10-0073/DC1. 1423771_at Prkcdbp protein kinase C, delta binding protein 1.15 10.96 11.02 9.66 10.02 1436876_at Rgs7bp regulator of G-protein signalling 7 binding protein 1.13 8.59 8.44 7.55 7.22 1447851_x_at Atp10a ATPase, class V, type 10A 1.93 7.74 7.26 5.25 5.89 1415822_at Scd2 stearoyl-Coenzyme A desaturase 2 1.47 12.69 12.98 11.12 11.61 1448280_at Syp synaptophysin 1.10 7.35 7.31 6.05 6.41 1449249_at Pcdh7 protocadherin 7 1.22 8.31 8.70 7.19 7.38 1418713_at Pcbd1 pterin 4 alpha carbinolamine dehydratase 1 1.01 7.95 7.81 6.72 7.00 1427422_at EG624219 predicted gene, EG624219 1.29 8.10 8.59 7.08 7.04 1449901_a_at Map3k6 mitogen-activated protein kinase kinase kinase 6 1.03 8.37 8.24 7.42 7.11 1419149_at Serpine1 serine (or cysteine) peptidase inhibitor, clade E, member 1 1.15 8.51 8.38 7.10 7.49 1441206_at Synpo2 synaptopodin 2 1.21 9.27 9.21 7.81 8.26 1415993_at Sqle squalene epoxidase 1.13 8.78 9.03 7.62 7.94 1456563_at 4933429F08Rik RIKEN cDNA 4933429F08 gene 1.09 6.28 5.93 4.94 5.09 1417430_at Cdr2 cerebellar degeneration-related 2 1.19 9.23 9.34 7.88 8.32 1416434_at Bcl2l10 Bcl2-like 10 1.06 6.68 6.85 5.87 5.54 1429571_a_at Spaca1 sperm acrosome associated 1 1.10 6.93 7.34 6.10 5.98 1418497_at Fgf13 fibroblast growth factor 13 1.33 10.11 10.12 8.50 9.08 1434581_at 2410066E13Rik RIKEN cDNA 2410066E13 gene 1.10 9.47 9.62 8.24 8.65 1424631_a_at Ighg Immunoglobulin heavy chain (gamma polypeptide) 2.21 11.15 11.12 9.47 8.38 1422533_at Cyp51 cytochrome P450, family 51 1.29 7.32 7.54 5.88 6.41 1418879_at Fam110c family with sequence similarity 110, member C 1.50 7.90 7.97 6.79 6.08 1418547_at Tfpi2 tissue factor pathway inhibitor 2 1.13 7.35 7.45 6.52 6.03 1454623_at Cpa2 carboxypeptidase A2, pancreatic 1.12 6.00 6.27 4.80 5.23 1423596_at Nek6 NIMA (never in mitosis gene a)-related expressed kinase 6 1.02 8.82 8.82 7.59 8.02 1433696_at Hn1l hematological and neurological expressed 1-like 1.00 8.22 8.58 7.29 7.50 1442051_at Hist2h3c1 histone cluster 2, H3c1 1.54 8.82 8.87 7.70 6.91 1436590_at Ppp1r3b protein phosphatase 1, regulatory (inhibitor) subunit 3B 1.28 9.47 9.80 8.64 8.07 1435484_at Slc5a3 solute carrier family 5 (inositol transporters), member 3 1.05 11.58 11.59 10.29 10.79 1434695_at Dtl denticleless homolog (Drosophila) 1.12 6.37 6.31 4.94 5.50 1439885_at Hoxc5 homeo box C5 1.20 8.96 9.11 7.53 8.14 1444089_at Spnb2 beta 2 1.10 9.17 9.21 7.82 8.38 1450871_a_at Bcat1 branched chain aminotransferase 1, cytosolic 1.02 6.66 6.62 5.36 5.87 1425681_a_at Prnd prion protein dublet 1.46 6.18 6.93 4.89 5.31 1426858_at Inhbb inhibin beta-B 1.16 9.63 9.64 8.13 8.82 1434411_at Col12a1 collagen, type XII, alpha 1 1.02 6.46 6.74 5.30 5.86 1452295_at Pmepa1 prostate transmembrane protein, androgen induced 1 1.01 9.45 9.58 8.82 8.20 Down-regulated genes HFD/CD (log2 Probe Symbol Description HFD 1 HFD 2 CD 1 CD 2 scale) 1422217_a_at Cyp1a1 cytochrome P450, family 1, subfamily a, polypeptide 1 -3.01 4.72 4.75 7.88 7.62 1419669_at Prtn3 proteinase 3 -2.06 7.84 7.89 10.03 9.83 1438403_s_at Malat1 metastasis associated lung adenocarcinoma transcript 1 (non-coding RNA) -1.47 9.10 9.06 10.51 10.59 1439117_at Clmn calmin -1.26 7.28 7.29 8.57 8.51 1452354_at 2810459M11Rik RIKEN cDNA 2810459M11 gene -1.20 4.97 5.09 6.24 6.22 1419420_at St6galnac5 ST6-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 -1.39 7.65 7.82 9.01 9.24 1448792_a_at Cyp2f2 cytochrome P450, family 2, subfamily f, polypeptide 2 -1.76 9.80 10.04 11.89 11.47 1456621_at Fam13a family with sequence similarity 13, member A -1.29 6.30 6.57 7.74 7.71 1445229_at Dgat1 diacylglycerol O-acyltransferase 1 -1.24 6.53 6.56 7.91 7.66 1435336_at Celsr2 cadherin, EGF LAG seven-pass G-type receptor 2 (flamingo homolog, Drosophila) -1.02 7.78 7.63 8.75 8.70 1429262_at Rassf6 Ras association (RalGDS/AF-6) domain family member 6 -1.06 5.20 5.13 6.33 6.12 1426154_s_at Mup3 major urinary protein 3 -1.37 11.41 11.21 12.87 12.50 1435663_at Esr1 estrogen receptor 1 (alpha) -1.03 7.75 7.83 8.91 8.72 1449051_at Ppara peroxisome proliferator activated receptor alpha -1.42 7.25 7.44 8.96 8.56 1424099_at Gpx8 glutathione peroxidase 8 (putative) -1.40 10.11 10.00 11.69 11.22 1440222_at Sod1 superoxide dismutase 1, soluble -1.05 6.32 6.62 7.46 7.59 1448609_at Tst thiosulfate sulfurtransferase, mitochondrial -1.61 9.34 9.50 11.33 10.71 1417084_at Eif4ebp2 eukaryotic translation initiation factor 4E binding protein 2 -1.07 6.99 7.34 8.25 8.23 1443749_x_at Slc1a3 solute carrier family 1 (glial high affinity glutamate transporter), member 3 -1.11 10.00 9.93 11.27 10.89 1434110_x_at OTTMUSG00000007486 predicted gene, OTTMUSG00000007486 -1.46 11.28 10.76 12.74 12.22 1420851_at Pard6g par-6 partitioning defective 6 homolog gamma (C. elegans) -1.15 8.37 8.28 9.74 9.21 1435860_at Slc5a6 solute carrier family 5 (sodium-dependent vitamin transporter), member 6 -1.46 6.97 7.11 8.91 8.09 1418446_at Slc16a2 solute carrier family 16 (monocarboxylic acid transporters), member 2 -1.06 7.61 7.59 8.96 8.36 1417496_at Cp -1.08 6.46 7.09 7.82 7.90 1450407_a_at Anp32a acidic (leucine-rich) nuclear phosphoprotein 32 family, member A -1.46 8.69 7.77 9.69 9.68 1438798_at 4931406P16Rik RIKEN cDNA 4931406P16 gene -1.15 6.67 7.36 8.19 8.13 1424945_at Chrdl1 chordin-like 1 -1.06 6.05 6.56 7.55 7.19 1454655_at Dgkd diacylglycerol kinase, delta -1.01 5.52 6.09 6.73 6.91 1425668_a_at St3gal4 ST3 beta-galactoside alpha-2,3-sialyltransferase 4 -1.11 7.52 7.94 9.10 8.57 1437303_at Il6st interleukin 6 signal transducer -1.21 8.08 8.86 9.64 9.72 1453255_at Slc43a1 solute carrier family 43, member 1 -1.61 7.02 7.40 9.33 8.30 1416835_s_at Amd1 S-adenosylmethionine decarboxylase 1 -1.35 8.29 8.79 10.27 9.51

©2010 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/cgi/content/full/db10-0073/DC1.

Supplemental Table 2. Uniquely up- and down-regulated genes in the inguinal fat pads of MMP14 haploinsufficient ( MMP14 +/−+/−+/− ) mice in response to nutritional change (HFD versus CD)

Up-regulated genes HFD/CD (log2 Probe Symbol Description HFD 1 HFD 2 CD 1 CD 2 scale) 1416023_at Fabp3 fatty acid binding protein 3, muscle and heart 3.24 8.20 11.72 6.53 6.91 1448680_at Serpina1c serine (or cysteine) peptidase inhibitor, clade A, member 1C 2.52 10.08 6.69 6.47 5.27 1420553_x_at Serpina1a serine (or cysteine) peptidase inhibitor, clade A, member 1A 2.33 7.47 6.85 5.14 4.52 1430886_at 1700112E06Rik RIKEN cDNA 1700112E06 gene 1.95 7.33 6.81 6.08 4.16 1418197_at Ucp1 uncoupling protein 1 (mitochondrial, proton carrier) 1.62 10.59 12.96 9.97 10.33 1422978_at Cybb cytochrome b-245, beta polypeptide 1.39 7.64 8.12 7.05 5.93 1416529_at Emp1 epithelial membrane protein 1 1.34 11.98 11.26 10.48 10.08 1419383_at S100b S100 protein, beta polypeptide, neural 1.26 6.88 8.40 6.67 6.08 1422704_at Gyk glycerol kinase 1.25 8.28 10.65 8.19 8.23 1430887_s_at 1700112E06Rik RIKEN cDNA 1700112E06 gene 1.25 8.26 7.91 7.33 6.34 1423294_at Mest mesoderm specific transcript 1.24 9.59 8.20 7.65 7.66 1447845_s_at Vnn1 vanin 1 1.23 7.95 6.85 5.57 6.78 1455447_at D430019H16Rik RIKEN cDNA D430019H16 gene 1.22 8.90 8.18 7.52 7.13 1417356_at Peg3 paternally expressed 3 1.21 7.87 6.80 5.68 6.56 1422561_at Adamts5 a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 5 (aggrecanase-2) 1.21 11.18 10.40 9.80 9.37 1451713_a_at Fcer2a Fc receptor, IgE, low affinity II, alpha polypeptide 1.20 7.80 8.48 7.31 6.58 1417673_at Grb14 growth factor receptor bound protein 14 1.19 9.52 9.20 8.60 7.74 1423866_at Serpina3k serine (or cysteine) peptidase inhibitor, clade A, member 3K 1.18 8.51 5.67 5.13 6.69 1422155_at Hist2h3c2 histone cluster 2, H3c2 1.15 7.65 7.58 6.61 6.32 1418486_at Vnn1 vanin 1 1.14 9.44 8.28 7.30 8.14 1422703_at Gyk glycerol kinase 1.12 6.03 7.83 5.94 5.68 1417688_at Fam20c family with sequence similarity 20, member C 1.12 8.31 7.71 7.19 6.60 1426157_a_at Cd209b CD209b antigen 1.11 9.24 9.21 9.45 6.76 1452646_at Trp53inp2 transformation related protein 53 inducible nuclear protein 2 1.11 12.54 12.37 11.28 11.41 1420722_at Elovl3 elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 3 1.09 6.07 9.98 6.72 7.15 1418709_at Cox7a1 cytochrome c oxidase, subunit VIIa 1 1.09 8.80 11.25 9.16 8.73 1450286_at Npr3 natriuretic peptide receptor 3 1.06 8.86 7.58 7.43 6.89 1433443_a_at LOC100040592 similar to Hmgcs1 protein 1.06 11.55 11.85 10.77 10.52 1418282_x_at Serpina1b serine (or cysteine) preptidase inhibitor, clade A, member 1B 1.06 9.39 7.95 7.48 7.74 1436876_at Rgs7bp regulator of G-protein signalling 7 binding protein 1.06 8.92 8.55 7.74 7.63 1448550_at Lbp lipopolysaccharide binding protein 1.04 10.15 8.53 8.63 7.96 1455318_at Timd4 T-cell immunoglobulin and mucin domain containing 4 1.04 9.19 9.59 9.21 7.49 1451513_x_at Serpina1b serine (or cysteine) preptidase inhibitor, clade A, member 1B 1.04 8.76 7.44 6.93 7.20 1456895_at Cd209b CD209b antigen 1.03 9.29 9.25 9.49 6.98 1426170_a_at Cd8b1 CD8 antigen, beta chain 1 1.03 9.63 10.40 9.15 8.81 1437559_at Rgs7bp regulator of G-protein signalling 7 binding protein 1.02 8.33 7.94 7.12 7.09 1451563_at Emr4 EGF-like module containing, mucin-like, hormone receptor-like sequence 4 1.02 6.97 7.30 6.51 5.72 1456395_at Ppargc1a peroxisome proliferative activated receptor, gamma, 1 alpha 1.01 7.75 8.46 6.97 7.22 1449498_at Marco receptor with collagenous structure 1.01 9.43 9.58 9.45 7.54

©2010 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/cgi/content/full/db10-0073/DC1. Down-regulated genes HFD/CD (log2 Probe Symbol Description HFD 1 HFD 2 CD 1 CD 2 scale) 1427026_at Myh4 myosin, heavy polypeptide 4, -4.72 7.42 4.36 9.45 11.76 1417464_at Tnnc2 C2, fast -4.12 8.34 5.04 9.88 11.74 1417614_at Ckm creatine kinase, muscle -3.78 7.65 5.33 9.16 11.37 1427735_a_at Acta1 , alpha 1, skeletal muscle -3.77 8.83 6.59 10.51 12.45 1417653_at Pvalb parvalbumin -3.72 7.55 5.21 8.99 11.21 1450118_a_at Tnnt3 troponin T3, skeletal, fast -3.71 6.99 4.88 8.36 10.94 1419312_at Atp2a1 ATPase, Ca++ transporting, , fast twitch 1 -3.56 7.46 5.62 9.06 11.14 1416889_at Tnni2 , skeletal, fast 2 -3.35 7.55 6.04 9.11 11.18 1418677_at Actn3 alpha 3 -3.35 6.62 4.86 7.79 10.39 1448371_at Mylpf , phosphorylatable, fast skeletal muscle -3.23 7.41 5.87 8.88 10.86 1455736_at Mybpc2 myosin binding protein C, fast-type -2.77 5.85 5.21 7.28 9.32 1427445_a_at Ttn -2.74 6.08 5.46 7.84 9.18 1426143_at Trdn -2.68 5.04 4.46 6.80 8.05 1417404_at Elovl6 ELOVL family member 6, elongation of long chain fatty acids (yeast) -2.63 9.47 10.65 12.68 12.70 1417403_at Elovl6 ELOVL family member 6, elongation of long chain fatty acids (yeast) -2.62 8.44 9.77 11.68 11.76 1448602_at Pygm muscle glycogen phosphorylase -2.51 5.88 5.12 6.90 9.11 1425326_at Acly ATP citrate -2.34 9.05 10.32 12.30 11.76 1460202_at Myoz1 myozenin 1 -2.34 5.88 5.70 7.17 9.08 1427446_s_at Ttn titin -2.34 6.13 5.96 7.69 9.07 1438609_x_at Tnni2 troponin I, skeletal, fast 2 -2.25 5.28 4.66 6.64 7.81 1424631_a_at Ighg Immunoglobulin heavy chain (gamma polypeptide) -2.17 6.75 6.99 10.02 8.05 1418373_at Pgam2 phosphoglycerate mutase 2 -2.12 6.04 5.19 6.88 8.60 1422598_at Casq1 1 -2.11 6.59 5.47 6.76 9.52 1423145_a_at Tcap titin-cap -2.10 5.95 5.17 7.18 8.14 1449577_x_at Tpm2 2, beta -2.02 5.21 5.18 6.38 8.05 1427312_at Cmya5 cardiomyopathy associated 5 -1.91 5.24 5.03 6.19 7.89 1416639_at Slc2a5 solute carrier family 2 (facilitated glucose transporter), member 5 -1.87 6.13 6.07 8.22 7.73 1419149_at Serpine1 serine (or cysteine) peptidase inhibitor, clade E, member 1 -1.83 7.41 5.83 8.58 8.33 1422217_a_at Cyp1a1 cytochrome P450, family 1, subfamily a, polypeptide 1 -1.77 4.89 5.10 6.84 6.68 1435188_at Gm129 gene model 129, (NCBI) -1.75 6.30 5.96 7.75 8.02 1438239_at Mid1 midline 1 -1.74 7.95 8.33 10.02 9.75 1427503_at AI324046 expressed sequence AI324046 -1.71 5.97 6.59 8.96 7.02 1425824_a_at Pcsk4 proprotein convertase subtilisin/kexin type 4 -1.71 5.87 5.82 7.38 7.73 1423049_a_at Tpm1 tropomyosin 1, alpha -1.65 8.98 8.64 9.42 11.51 1451666_at Acly ATP citrate lyase -1.65 11.37 12.47 13.68 13.46 1436605_at Tkt transketolase -1.59 6.90 6.99 8.69 8.38 1418025_at Bhlhe40 basic helix-loop-helix family, member e40 -1.55 8.83 8.62 10.29 10.27 1427422_at EG624219 predicted gene, EG624219 -1.50 6.85 6.91 8.25 8.51 1448194_a_at H19 H19 fetal liver mRNA -1.45 4.95 4.84 6.15 6.54 1446284_at Mtss1 metastasis suppressor 1 -1.43 7.67 8.06 9.27 9.31 1417092_at Pth1r parathyroid hormone 1 receptor -1.40 7.58 7.53 9.06 8.87 1430307_a_at Me1 malic 1, NADP(+)-dependent, cytosolic -1.39 11.64 11.96 13.18 13.21 1435860_at Slc5a6 solute carrier family 5 (sodium-dependent vitamin transporter), member 6 -1.39 7.64 7.50 8.86 9.06 1424099_at Gpx8 glutathione peroxidase 8 (putative) -1.34 10.12 10.55 11.39 11.97 1439459_x_at Acly ATP citrate lyase -1.31 11.15 12.16 13.17 12.77 1417461_at Cap1 CAP, adenylate cyclase-associated protein 1 (yeast) -1.30 6.09 7.01 8.34 7.36 1427306_at Ryr1 1, skeletal muscle -1.28 5.64 5.66 6.29 7.57 1420545_a_at Chn1 chimerin (chimaerin) 1 -1.28 7.01 6.66 8.10 8.13 1452183_a_at Meg3 maternally expressed 3 -1.27 8.00 7.62 8.95 9.22 1416632_at Me1 malic enzyme 1, NADP(+)-dependent, cytosolic -1.26 11.96 12.42 13.40 13.51 1417169_at Usp2 ubiquitin specific peptidase 2 -1.25 7.98 8.14 8.89 9.73 1442656_at Elovl6 ELOVL family member 6, elongation of long chain fatty acids (yeast) -1.23 5.15 5.58 6.45 6.74 1425763_x_at Igh immunoglobulin heavy chain complex -1.22 9.36 8.65 10.74 9.69 1417168_a_at Usp2 ubiquitin specific peptidase 2 -1.21 8.01 8.22 8.94 9.72 1451447_at Cuedc1 CUE domain containing 1 -1.21 5.53 5.35 7.29 6.01 1421653_a_at Igh immunoglobulin heavy chain complex -1.19 9.91 9.48 11.37 10.41 1453839_a_at Pi16 peptidase inhibitor 16 -1.18 10.80 5.47 9.12 9.51 1436713_s_at Meg3 maternally expressed 3 -1.18 6.49 5.63 7.13 7.35 1422479_at Acss2 acyl-CoA synthetase short-chain family member 2 -1.17 10.19 11.07 12.00 11.60 1434185_at Acaca acetyl-Coenzyme A carboxylase alpha -1.17 11.20 11.47 12.55 12.44 1446542_at Acss2 acyl-CoA synthetase short-chain family member 2 -1.16 5.35 5.96 6.95 6.69 1452905_at Meg3 maternally expressed 3 -1.16 8.73 8.14 9.70 9.50 1452741_s_at Gpd2 glycerol dehydrogenase 2, mitochondrial -1.16 6.00 7.29 7.77 7.83 1449461_at Rbp7 retinol binding protein 7, cellular -1.16 8.76 8.91 9.92 10.06 1427056_at Adamts15 a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 15 -1.14 5.94 6.45 7.06 7.61 1424305_at Igj immunoglobulin joining chain -1.13 8.73 8.57 10.74 8.84 1416236_a_at Mpzl2 protein zero-like 2 -1.13 6.42 7.22 7.91 8.00 1429381_x_at Igh immunoglobulin heavy chain complex -1.11 8.97 8.43 10.39 9.22 1417607_at Cox6a2 cytochrome c oxidase, subunit VI a, polypeptide 2 -1.11 6.02 5.73 6.66 7.30 1426758_s_at Meg3 maternally expressed 3 -1.10 7.69 7.23 8.38 8.73 1422478_a_at Acss2 acyl-CoA synthetase short-chain family member 2 -1.08 9.39 10.58 11.30 10.83 1420693_at Myom1 myomesin 1 -1.08 5.86 5.92 6.48 7.46 1451015_at Tkt transketolase -1.08 12.24 12.44 13.48 13.35 1425385_a_at Igh-6 immunoglobulin heavy chain 6 (heavy chain of IgM) -1.08 6.61 7.57 9.58 6.75 1448649_at Enpep glutamyl aminopeptidase -1.06 9.99 9.52 10.81 10.82 1418174_at Dbp D site albumin promoter binding protein -1.05 9.77 9.30 10.59 10.58 1417951_at Eno3 enolase 3, beta muscle -1.04 8.65 8.89 9.27 10.35 1434110_x_at OTTMUSG00000007486 predicted gene, OTTMUSG00000007486 -1.03 10.14 10.43 11.13 11.50 1434223_at 1810007P19Rik RIKEN cDNA 1810007P19 gene -1.02 6.86 6.76 7.72 7.95 1439117_at Clmn calmin -1.02 8.17 7.67 8.73 9.15 1426154_s_at Mup3 major urinary protein 3 -1.02 10.33 10.97 11.50 11.84 1449038_at Hsd11b1 hydroxysteroid 11-beta dehydrogenase 1 -1.02 11.50 11.51 12.40 12.65 1434722_at Ampd1 adenosine monophosphate deaminase 1 (isoform M) -1.01 5.68 5.37 6.09 6.99

©2010 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/cgi/content/full/db10-0073/DC1. Supplemental Table 3. Minor frequencies of MMP14 SNPs in a preliminary population (n=48)

SNP Minor Allele Frequency rs17211964 0.011 rs17884825 0 rs17880833 0 rs2269213 0.208 rs17884841 0 rs2236302 0.16 rs17881628 0.011 rs2236303 0.447 rs2236304 0.448 rs2236305 0.385 rs2236306 0.385 rs2236307 0.385 rs17884719 0 rs17880907 0 rs17878814 0 rs3751489 0

Supplemental Table 4. Pairwise linkage disequilibrium coefficients (r 2) among MMP14 SNPs in a preliminary population rs17211964 rs2269213 0.04 rs2236302 0.056 0.467 rs17881628 0 0.003 0.002 rs2236303 0.009 0.142 0.153 0.013 rs2236304 0.009 0.138 0.153 0.013 1 rs2236305 0.017 0.015 0.118 0.007 0.501 0.509 rs2236306 0.017 0.015 0.118 0.007 0.501 0.509 1 rs2236307 0.017 0.015 0.118 0.007 0.501 0.509 1 1 rs17211964 rs2269213 rs2236302 rs17881628 rs2236303 rs2236304 rs2236305 rs2236306 rs2236307

©2010 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/cgi/content/full/db10-0073/DC1. Figure S1. Normal development in MMP14 -haploinsufficient mice. (A) Scanning electron micrographs of inguinal fat pads isolated from MMP14 +/+ and MMP14 +/− mice. Bar = 10 µm (B) Body weights of 3 month-old MMP14 +/+ and MMP14 +/− mice. Mean ± 1 SD (n=6). (C) Expression of mature adipocyte markers. Semi-quantitative PCR results for fatty acid binding protein 4 (aP2), lipoprotein lipase (LPL), and insulin receptor (IR) with control 36B4 are shown.

Figure S2. Early-onset gene regulation in ECM remodeling and lipid biosynthesis by high-fat diet feeding . High-fat diet induces in the pathways of collagen remodeling/integrin signaling (blue) and lipid/cholesterol biosynthesis (red). Changes in the expression levels of representative genes are shown as fold- increases (high fat diet/control diet). MMP14 wild-type ( MMP14 +/+ , blue) and haploinsufficient ( MMP14 +/− , red) mice are compared in a replicate data set.

©2010 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/cgi/content/full/db10-0073/DC1.