Association of MMP-8 with obesity, smoking and insulin resistance
Background Obesity has been recognized as a state of subclinical inflammation resulting in a loss of insulin receptors and decreased insulin sensitivity. We here studied in vivo the role of circulating matrix metalloproteinase‐8 (MMP‐8) among young healthy twin adults. Also, in vitro analysis of the...
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Published in | European journal of clinical investigation Vol. 46; no. 9; pp. 757 - 765 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Blackwell Publishing Ltd
01.09.2016
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Subjects | |
Online Access | Get full text |
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Summary: | Background
Obesity has been recognized as a state of subclinical inflammation resulting in a loss of insulin receptors and decreased insulin sensitivity. We here studied in vivo the role of circulating matrix metalloproteinase‐8 (MMP‐8) among young healthy twin adults. Also, in vitro analysis of the cleavage of human insulin receptor (INSR) by MMP‐8 was investigated as well its inhibition by doxycycline and other MMP‐8 inhibitor, Ilomastat/GM6001, which are broad‐spectrum MMP inhibitors.
Materials and methods
We analysed serum MMP‐8 levels by a time‐resolved immunofluorometric assay in obese (n = 34), overweight (n = 76) and normal weight (n = 130) twin individuals. The effect of MMP‐8 on INSR and the effects of synthetic MMP‐8 inhibitors, doxycycline and Ilomastat/GM6001, were studied by SDS‐PAGE.
Results
We found that in obese individuals relative to normal weight individuals, the serum MMP‐8 levels and MMP‐8/TIMP‐1 ratio were significantly increased (P = 0·0031 and P = 0·031, respectively). Among normal weight and obese individuals, also smoking significantly increases serum MMP‐8 and MMP‐8/TIMP‐1 ratio. In vitro, we found that INSR was degraded by MMP‐8 and this was inhibited by doxycycline and Ilomastat/GM6001.
Conclusions
Obesity associated with elevated circulating MMP‐8 found among young adults may contribute to progression of insulin resistance by cleaving INSR. This INSR cleavage by MMP‐8 can be inhibited by synthetic MMP‐8 inhibitors such as doxycycline. In addition to obesity, also smoking independently explained increased MMP‐8 levels. Our results suggest that MMP‐8 is an essential mediator in systemic subclinical inflammatory response in obesity, and a potential drug target. |
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Bibliography: | Academy of Finland Oulu University Hospital KEVO Novo Nordisk Foundation istex:4CC7056908B52104C62CB8A5E18B74F301633A1B ark:/67375/WNG-XNKNRDQB-Q Finnish Cardiovascular Research Foundation ArticleID:ECI12649 Helsinki University Hospital EVO Erasmus International Student Exchange and the Finnish Doctoral Program in Oral Sciences ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0014-2972 1365-2362 1365-2362 |
DOI: | 10.1111/eci.12649 |