Microfibrillar-associated protein 5 is linked with markers of obesity-related extracellular matrix remodeling and inflammation

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)-1 beta 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. Nutrition and Diabetes (2011) 1, e15; doi:10.1038/nutd.2011.10; published online 29 August 2011