Association of metabolic parameters and rs726344 in FNDC5 with serum irisin concentrations.

BACKGROUND/OBJECTIVES: Irisin has been suggested as a novel myokine with beneficial effects in rodents. However, previous data in humans showed conflicting results regarding its association with metabolic phenotypes and regulation of secretion. Furthermore, although an association of rs726344 in FNDC5 (fibronectin type III domain containing 5) coding for irisin with insulin sensitivity was reported, the effects of genetic variation at this locus on irisin serum levels have not been investigated, so far. Therefore, we investigated circulating irisin and the associations with rs726344 in a cohort of >1000 subjects. SUBJECTS/METHODS: Irisin serum concentrations were measured with enzyme-linked immunosorbent assay. Associations with metabolic parameters including renal function, glucose and lipid metabolism, inflammation, as well as adipokine profiles, were assessed in regression models. Dynamic changes of serum irisin were investigated during oral glucose tolerance test (OGTT) in a subset of the cohort (n=136). rs726344 was genotyped in all subjects and analyzed for associations with serum irisin and traits of the metabolic syndrome. RESULTS: Irisin was negatively associated with fat mass, fasting glucose and dyslipidemia but not with other adipokines. Moreover, irisin decreased during an OGTT in a subcohort comprising subjects with normal glucose tolerance, impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus. rs726344 was not associated with serum irisin levels or with other anthropometric and biochemical parameters. CONCLUSIONS: Circulating irisin levels are associated with a beneficial metabolic profile but not with other adipokines and not with rs726344 in our cohort. Our data suggest a potential favorable role of irisin in the regulation of metabolism.

Circulating adipocyte fatty acid binding protein is increased in chronic and acute renal dysfunction.

BACKGROUND AND AIMS: The adipokine adipocyte fatty acid binding protein (AFABP) is positively associated with the development of the metabolic syndrome, diabetes mellitus, and cardiovascular disease. We hypothesized that AFABP also increases with deteriorating renal function. METHODS AND RESULTS: Serum AFABP levels were quantified by enzyme linked immunosorbent assay in 532 patients with chronic kidney disease (CKD) covering the whole spectrum of estimated glomerular filtration rate (eGFR) categories from G1 to G5 (study population 1). Furthermore, AFABP was measured in 32 patients before and within 30 h after elective unilateral nephrectomy, a model of acute kidney dysfunction (AKD) (study population 2). Moreover, circulating AFABP was investigated in rats undergoing bilateral nephrectomy (BNE) as compared to sham-operated animals. Median serum AFABP levels adjusted for age, gender, and body mass index significantly increased with increasing eGFR category (G1: 22.0 µg/l; G2: 34.6 µg/l; G3: 56.7 µg/l; G4: 95.2 µg/l; and G5: 173.9 µg/l). Furthermore, renal dysfunction remained positively associated with AFABP in multivariate analysis in this cohort. In patients undergoing unilateral nephrectomy, AFABP increased significantly after surgery (42.1 µg/l) as compared to pre-surgical values (29.3 µg/l). Furthermore, relative changes of post-to-pre-surgical AFABP levels were independently associated with relative changes of post-to-pre-surgical creatinine concentrations. After BNE in rats, AFABP increased significantly as compared to sham-operated animals. CONCLUSIONS: We show that AFABP is significantly elevated in CKD and AKD patients. Furthermore, measures of renal function are associated with circulating AFABP. Moreover, animal experiments indicate that AFABP levels strongly depend on renal function.