Supplemental Table 1. Sequences of the primers and TaqMan® probes

Gene (GenBank accession) / Oligonucleotide sequence (5’-3’)
LCN2 (NM_005564)
Forward / CCCAGCCCCACCTCTGA
Reverse / CTTCCCCTGGAATTGGTTGTC
TaqMan® Probe / FAM-CAAGGTCCCTCTGCAGCAGAACTTCCA-TAMRA
RARRES2 (NM_002889)
Forward / GGAAGAAACCCGAGTGCAAAG
Reverse / CGCAGAACTTGGGTCTCTATGG
TaqMan® Probe / FAM-AGGCCCAATGGGAGGAAACGGAAA-TAMRA
SPP1 (NM_000582)
Forward / CATCCAGTACCCTGATGCTACAGA
Reverse / GGCCTTGTATGCACCATTCAA
TaqMan® Probe / FAM-ACATCACCTCACACATGGAAAGCGAGGA-TAMRA
YKL40 (NM_001276)
Forward / GGACGGAGAGACAAACAGCATT
Reverse / CCTGGCTGGGCTTCCTTTAT
TaqMan® Probe / FAM-CCACCCTAATCAAGGAAATGAAGGCC-TAMRA

LCN2, lipocalin 2; RARRES2, chemerin; SPP1, osteopontin; YKL40, chitinase 3-like 1.

Supplemental Table 2. Effects of weight loss in obese patients after Roux-en-Y gastric bypass (RYGB).

Before WL / After WL
n / 36 / 36
Age (years) / 42  2 / 43  3
Weight (kg) / 120.3  3.7 / 80.1  2.3***
BMI (kg/m2) / 44.7  1.1 / 31.8  0.7***
Body fat (%) / 53.1  0.9 / 36.7  1.4***
Waist (cm) / 124.4  2.6 / 95.5  1.9***
Hip (cm) / 132.5  2.4 / 106.7  1.7***
WHR / 0.94  0.01 / 0.89  0.01***
SBP (mm Hg) / 130 6 / 126  16
DBP (mm Hg) / 86  2 / 82  8
Fasting glucose (mg/dL) / 118  13 / 91  4*
Fasting insulin (U/mL) / 22.5  5.9 / 12.7  5.8***
HOMA / 7.7  3.2 / 4.4  2.6**
QUICKI / 0.301  0.011 / 0.339  0.015***
Triacylglycerols (mg/dL) / 144  11 / 90  7**
Total cholesterol (mg/dL) / 214  6 / 165  6***
LDL-cholesterol (mg/dL) / 139  5 / 93  5***
HDL-cholesterol (mg/dL) / 44  2 / 53  2**
Uric acid / 5.65  0.27 / 4.17  0.20***
Leptin (ng/mL) / 58.7  6.3 / 24.9  4.4***
CRP (mg/L) / 7.8  0.21 / 3.8  0.11
Fibrinogen (mg/dL) / 371  15 / 322  12**
Homocysteine (mol/L) / 7.9  0.6 / 8.7  0.9
AST (UI/L) / 19.8  2.3 / 17.9  1.8
ALT (UI/L) / 30.3  3.6 / 24.1  3.3
ALP (UI/L) / 119.4  7.4 / 112  6.7
-GT (UI/L) / 37.1  6.9 / 18.4  3.3***

ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CRP, C-reactive protein; DBP, diastolic blood pressure; -GT, -glutamyltransferase; HOMA, homeostasis model assessment; QUICKI, quantitative insulin sensitivity check index; SBP, systolic blood pressure; WHR, waist-to-hip ratio; WL, weight loss. Data are mean  SEM. Differences between groups were analyzed by two-tailed paired t-tests. *P<0.05, **P<0.01 and *** P<0.0001 vs before WL.

Legends for supplemental figures

Supplemental Figure 1.Tissue distribution ofWNT5A and SFRP5. Comparison of mRNA levels of (A) WNT5A and (B) SFRP5 in visceral (n=69) and subcutaneous (n=37) adipose tissue, peripheral mononuclear blood cells (PMBC) (n=66) and liver biopsies (n=60). Bars represent the mean  SEM of the ratio between the gene expressionto 18S rRNA. Differences between groups were analyzed by one-way ANOVA. The expression level in VAT was assumed to be 1. Differences between groups were analyzed by one-way ANOVA followed by Tukey’s tests. *P0.05 vs VAT and ††P<0.01 vs PMBC.

Supplemental Figure 2.Gene expression levels of receptor-like tyrosine kinase (ROR)-1 (A) and ROR2 (B) in VAT of LN, obese NG and obese T2D volunteers. Bars represent the mean  SEM of the ratio between the gene expression to 18S rRNA. The expression level in LN subjects was assumed to be 1 (LN: n=9; OB-NG: n=32; OB-T2D: n=28). Differences between groups were analyzed by one-way ANOVA followed by Tukey’s tests. *P<0.05 vs LN.

Supplemental Figure 3.Effect of SFRP5 (100 ng/mL) for 24 h on basal and WNT5A (100 ng/mL)-induced gene expression of inflammatory genes. Gene expression levels of (A) interleukin 6 (IL6), (B) interleukin 1 (IL1B), (C) tumor necrosis factor- (TNFA), (D) monocyte chemotactic protein 2 (CCL2), (E) matrix metalloproteinase 2 (MMP2), (F) matrix metalloproteinase 9 (MMP9), (G) lipocalin 2 (NGAL) and (H) osteopontin (SPP1) in human differentiated visceral adipocytes. Gene expression levels in unstimulated cells were assumed to be 1. Values are the mean  SEM (n=10 per group). Differences between groups were analyzed by one-way ANOVA followed by Tukey’s tests. *P<0.05 vs unstimulated and †P<0.05 vs WNT5A-stimulated cells.

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