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

Abstract

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.

A Systematic Review of the Effect of Lifestyle Interventions on Adipose Tissue Gene Expression: Implications for Carcinogenesis

“…In samples of subcutaneous abdominal adipose tissue, leptin (LEP) expression was reported in six studies . In studies of diet only or in the diet‐only arm of combined dietary + exercise change, all studies reported a decrease in LEP expression with weight loss ( n = 4) with a statistically significant decrease reported in two studies . However, a decrease in expression was also noted in the energy surplus intervention in both study arms .…”

Downregulation of CPPED1 Expression Improves Glucose Metabolism In Vitro in Adipocytes

“…The design of the Gene Expression in Obesity and Insulin Resistance (GENOBIN) study has been reported earlier (2,3). Altogether, 46 overweight or obese (BMI 28–40 kg/m 2 ) subjects 40–70 years of age were randomly assigned to one of two groups: a weight-reduction group ( n = 28) or a weight-maintenance control group ( n = 18) (2).…”

“…In searching new putative genes related to obesity and type 2 diabetes, we have previously demonstrated a multitude of changes in adipose tissue (AT) gene expression in response to weight reduction in individuals with metabolic syndrome (2,3). Among the downregulated genes was calcineurin-like phosphoesterase domain containing 1 ( CPPED1 ) (2); its function in AT is completely unknown.…”

The Extracellular Matrix Protein MAGP1 Is a Key Regulator of Adipose Tissue Remodeling During Obesity

“…They demonstrated that weakening of the adipose tissue ECM by genetic disruption of collagen VI resulted in considerable improvement of the metabolic phenotype in the context of a high-fat diet and in mice with the ob/ob mutation. In addition, a study by Vaittinen et al (11) showed that the microfibrillarassociated protein 5 (MFAP5) is highly expressed in human adipose tissue and is correlated with markers of insulin resistance, suggesting that MFAP5 is related to ECM remodeling during the development of obesity. Kolehmainen et al (12) recently studied the effect of weight loss on gene expression in the adipose tissue of obese individuals with impaired metabolic function and found that genes regulating the ECM and cell death showed a strong downregulation after long-term weight reduction.…”