Gene expression of FNDC5 and related genes in gluteal subcutaneous adipose tissue and plasma irisin levels after acute inactivity

Aim: Irisin, a cleavage product of FNDC5 gene, is an exercise-induced myokine involved in muscle-adipose crosstalk with positive effects on energy metabolism. We evaluated the effect of acute inactivity on plasma irisin levels on gluteal subcutaneous adipose tissue (g-SAT) gene expression of FNDC5 and of genes involved in its network. Methods: 23 healthy male volunteers,7 “Young” (18-25 y) and 16 “Older” (55-65 y) underwent 14-days of continuous horizontal bed rest (BR). At baseline (BR1) and after 14 days of BR (BR14) a blood sample for biochemical analysis and plasma irisin dosage was collected. Moreover we performed a g-SAT biopsy (7 representative samples) in order to obtain RNA for subsequent gene expression analysis with microarray. We evaluated differences in gene expression of FNDC5 and a list of 56 genes, identified trough a review of literature, potentially involved in irisin’s pathway. Results: At BR1 irisin did not differ between Young and Older (4,58 vs 5,01 mg/L; p 0.74). At BR14, we observed a significant increase of irisin in both groups (Y from 4,58 to 6,07; O from 5,01 to 7,05; p 0,01). Furthermore, after BR, FNDC5 was overexpressed (FC 1,8; p 0,002) in gluteal adipocyte and a different expression of 10/56 genes involved in irisin pathway was observed (p 0,0003). Conclusions: Our data suggest that irisin may play a role in metabolic adaptation following acute immobilization and could be the response of muscle against the detrimental effects of inactivity. This underlines the importance of irisin in the muscle-adipose tissue crosstalk to maintain the global homeostasis. P2.7.238. ABCA1 GENE EXPRESSION IN EPICARDIAL ADIPOSE TISSUE OF PATIENTS WITH CORONARY ARTERY DISEASE V. Miroshnikova 1, A. Panteleeva 1,2, I. Pobozheva 2, N. Razgildina 1, E. Polyakova 2, O. Belyaeva 2, O. Berkovitch 2, E. Baranova 2, S. Pchelina 1,2. 1 Petersburg Nuclear Physics Institute, Gatchina, Russia; 2 First Pavlov State Medical University, Saint-Petersburg, Russia Aim: Epicardial adipose tissue (EAT) can play an important role in the development of coronary artery disease (CAD). Abnormalities in adipose tissue cholesterol metabolism lead to its accumulation and subsequent adipocyte dysfunction. This can contribute to proinflammatory adipocytokine production, adipose tissue macrophages activation and coronary atherosclerosis progression. Cholesterol efflux from peripheral cells is regulated by ATP-binding cassette transporter ABCA1 playing a major role in the reverse cholesterol transport. However the impact of ABCA1 gene expression in EAT in the development of CAD is unknown. The aim of this study was to investigate the association of ABCA1 gene expression in EAT and paired subcutaneous adipose tissue (SAT) with CAD. Methods: EAT samples were obtained from CAD patients during coronary bypass surgery (N¼50) and from control persons without CAD - during heart valve surgery (N¼17). Atherosclerosis severity was evaluated by coronary angiography as a quantity of significant atherosclerotic lesions in different coronary pools. ABCA1 gene expression levels in adipose tissue samples were measured by real-time PCR. Results: ABCA1 mRNA levels in EAT were lowered in patients with severe CAD accompanied by atherosclerotic lesions of cerebral, internal carotid or lower extremities arteries when compared with not complicated CAD (p<0,001) and control group (p<0,01). This pattern was also reliably observed for SAT in the same patients (p<0,005). ABCA1 mRNA levels were significantly correlated with coronary atherosclerosis severity (p<0,005). Conclusions: Our results suggest that ABCA1 gene expression in EAT and SAT has important implications for atherosclerosis.