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Published on: June 3, 2016
Microfibrillar-associated protein 5 is linked with markers of obesity-related extracellular matrix remodeling and
M Vaittinen1, M Kolehmainen, U Schwab
1Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, Food and Health Research Centre, University of Eastern Finland, Kuopio, Finland.
Objective:
Microfibrillar-associated protein 5 (MFAP5) is an extracellular matrix (ECM) glycoprotein, which is colocalized with microfibrils in elastin networks. Its function in adipose tissue (AT) is not known. We have recently shown that the expression of MFAP5 is downregulated in AT along with weight reduction (WR) in persons with metabolic syndrome (MetS). The aim of this work was to study whether the change of MFAP5 mRNA expression in response to WR is associated with markers of adiposity, glucose metabolism and insulin resistance in human AT.
Design:
Weight reduction intervention study in parallel study design (The Genobin study). Altogether 46 obese subjects with impaired glucose tolerance and features of MetS were randomized to a WR (n=28) or a control group (n=18) lasting for 33 weeks.
Measurements:
Circulating glucose and insulin concentrations were measured and subcutaneous AT biopsies were performed before and after the intervention. The mRNA expression was studied by quantitative real-time PCR (QPCR).
Results:
QPCR of human AT biopsy samples confirmed that MFAP5 is highly expressed in AT and its expression is decreased during WR. The mRNA expression of MFAP5 correlated positively with body mass index, and the change in MFAP5 mRNA expression during WR correlated positively with the change of body fat mass. Furthermore, the MFAP5 mRNA expression correlated negatively with circulating fasting concentrations of adiponectin and interleukin (IL)-1β and positively with leptin, insulin and IL-1Ra levels. In addition, the MFAP5 mRNA expression correlated positively with the mRNA expressions of peroxisome proliferator-activated receptor gamma, cyclin D2 and A disintegrin and metalloproteinase domain 12, genes involved in AT remodeling.
Conclusion:
This study demonstrates that MFAP5 is highly expressed in human AT and is correlated with markers of insulin resistance. Furthermore, it is possible that MFAP5 is related to ECM remodeling during development of obesity.
Insights
Microfibrillar-associated protein 5 (MFAP5) is highly expressed in adipose tissue and linked to insulin resistance. Its expression decreases with weight reduction and correlates with obesity markers, suggesting a role in extracellular matrix remodeling.
Area of Science:
- Biochemistry
- Metabolic Syndrome Research
- Adipose Tissue Biology
Background:
- Microfibrillar-associated protein 5 (MFAP5) is an extracellular matrix (ECM) glycoprotein found in elastin networks.
- Its role in adipose tissue (AT) function remains largely unknown.
- MFAP5 expression is downregulated in AT during weight reduction (WR) in individuals with metabolic syndrome (MetS).
Purpose of the Study:
- To investigate the association between MFAP5 mRNA expression changes in human AT in response to WR.
- To correlate these changes with markers of adiposity, glucose metabolism, and insulin resistance.
Main Methods:
- A 33-week WR intervention study (The Genobin study) involving 46 obese subjects with impaired glucose tolerance and MetS.
- Subcutaneous AT biopsies and circulating glucose/insulin measurements were performed before and after intervention.
- Quantitative real-time PCR (QPCR) was used to analyze MFAP5 mRNA expression.
Main Results:
- MFAP5 is highly expressed in human AT, with expression decreasing during WR.
- MFAP5 mRNA expression positively correlated with body mass index and body fat mass.
- MFAP5 expression showed correlations with adiponectin, interleukin (IL)-1β, leptin, insulin, IL-1Ra, and genes involved in AT remodeling.
Conclusions:
- MFAP5 is highly expressed in human AT and correlates with insulin resistance markers.
- MFAP5 may play a role in extracellular matrix remodeling during obesity development.
- Changes in MFAP5 expression during WR are linked to alterations in adiposity and metabolic markers.
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