Markers of remodeling in subcutaneous adipose tissue are strongly associated with overweight and insulin sensitivity in healthy non-obese men

Sissel Åkra, Tonje A Aksnes, Arnljot Flaa, Heidi B Eggesbø, Trine Baur Opstad, Ida U Njerve, Ingebjørg Seljeflot, Sissel Åkra, Tonje A Aksnes, Arnljot Flaa, Heidi B Eggesbø, Trine Baur Opstad, Ida U Njerve, Ingebjørg Seljeflot

Abstract

Alteration in extracellular matrix (ECM) in adipose tissues (AT) has been associated with insulin resistance, diabetes and obesity. We investigated whether selected biomarkers of ECM remodeling in AT in healthy subjects associated with the amount and distribution of AT and with glucometabolic variables. Subcutaneous AT and fasting blood samples from 103 middle-aged healthy non-obese men were used. AT gene expression and circulating levels of the biomarkers were quantified. Distribution of AT was assessed by computed tomography, separated into subcutaneous, deep subcutaneous and visceral AT. Insulin sensitivity was measured by glucose clamp technique. Metalloproteinase (MMP)-9, tissue inhibitor of MMP (TIMP)-1 and plasminogen activator inhibitor (PAI)-1 expression in AT correlated significantly to the amount of AT in all compartments (rs = 0.41-0.53, all p ≤ 0.01), and to insulin sensitivity, insulin, C-peptide, waist circumference and body mass index (BMI) (rs = 0.25-0.57, all p ≤ 0.05). MMP-9 was 5.3 fold higher in subjects with insulin sensitivity below median (p = 0.002) and 3.1 fold higher in subjects with BMI above median level (p = 0.013). In our healthy non-obese middle-aged population AT-expressed genes, central in remodeling of ECM, associated strongly with the amount of abdominal AT, overweight and insulin sensitivity, indicating AT-remodeling to play a role also in non-obese individuals. The remodeling process seems furthermore to associate significantly with glucometabolic disturbances.Trial registration: ClinicalTrials.gov, NCT01412554. Registered 9 August 2011, https://ichgcp.net/clinical-trials-registry/NCT01412554?term=NCT01412554 .

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Gene expression of the measured biomarkers in subcutaneous adipose tissue as related to glucometabolic variables dichotomized by median values and as related to being overweight (BMI > 25 kg/m2). p-values refer to Mann–Whitney U Test.
Figure 2
Figure 2
AT gene expression of MMP-9 related to groups combining subjects with low/high GDR and high/low BMI. Low GDR/High BMI: Subjects in the lowest quartile of GDR ( 26.3 kg/m2), (n = 11). Low GDR/Low BMI: Subjects in the lowest quartile of GDR and the three lowest quartiles of BMI, (n = 14). High GDR/High BMI: Subjects in the three upper quartiles of GDR (> 3.8 mg/kg/min) and highest quartile of BMI (> 26.3 kg/m2), (n = 14). High GDR/Low BMI: Subjects in the three upper quartiles of GDR and the three lowest quartiles of BMI, (n = 59).

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