The influence of non-small cell lung cancer cells on the expression of adipokines in brown adipose tissue

Introduction: Brown adipose tissue (BAT) increases energy expenditure and might be involved in the development of cancer cachexia. Non-small cell lung cancer (NSCLC) cells might induce BAT activation via an adipokine signalling promoting cachexia. Objectives: We aimed to find out whether NSCLC cells influence the expression of adipokines in preadipocytes and BAT involved in the development of BAT activation. Methods: Preadipocytes and differentiated BAT were cultured with conditioned media of six NSCLC cell lines (H1299, A549, H322, PC-9, H1650, H460), respectively. Protein levels of the key-adipokines adiponectin, fibroblast growth factor 21 (FGF21), and irisin involved in the activation of BAT were investigated in both supernatants and cell lysates of preadipocytes and BAT by enzyme-linked immunosorbent assay. Results: Undifferentiated preadipocytes showed higher FGF21 protein expression (p.e.) when cultured with conditioned medium from PC-9 cells. Higher irisin p.e. was observed in H1650 and H322 conditioned media compared with control medium. In differentiated BAT, FGF21 was increased when incubated with conditioned media from all NSCLC cell lines. BAT showed higher irisin p.e. in the media of H1650 and H322 cells but lower p.e. when cultured in H460 medium. Adiponectin p.e. in BAT were stimulated by the media of H1299, A549, H322, H460. Conclusions: PC-9 and H1650 media might potentially induce preadipocyte activation through FGF21 and irisin signalling, respectively. In differentiated BAT, NSCLC cell-derived media increase protein levels of all adipokines investigated. Therefore, BAT activation might play a role in the development of cancer cachexia.