Endocrine Abstracts

Background/objectives: Irisin is a novel myokine, released predominantly by skeletal muscle. Peripheral action of irisin improves glucose homeostasis, increases energy expenditure and induces browning of adipocytes, with therapeutic potential for use in weight loss. However, there are no human studies on the central role of irisin in the regulation of appetite or energy expenditure. This study sought to examine the potential central role of irisin, by demonstrating irisin in human cerebrospinal fluid (CSF) and hypothalamic sections. We also studied how different metabolic states may alter the effect of irisin, and their relationship with maternal and neonatal serum irisin levels.

Methods: Patients attending for elective Caesarean sections in a tertiary care teaching hospital were recruited. CSF, serum and neonatal cord blood were collected from 91 pregnant women; non-obese (n=34) obese (n=39) and those with gestational diabetes mellitus (GDM) (n=18). Irisin was assessed by an enzyme-linked immunosorbent assay which was validated in-house, using recombinant human irisin.

Results: Irisin was present in human CSF 32.0 (mean±S.E.M.) 1.5 ng/ml at a 20–30-fold lower concentration compared with serum irisin (799±34.5 ng/ml). Serum irisin did not differ between groups but CSF irisin correlated positively with serum irisin levels from non-obese and obese pregnant women (P<0.01), with CSF irisin significantly raised in GDM subjects (P<0.05). Independent of BMI, serum irisin correlated with HOMA IR (P<0.01), cholesterol, TG and HDL (P<0.01). Neonatal cord irisin levels (237±8.1 ng/ml) correlated with maternal serum irisin (r=0.29, P<0.05). Immunohistochemistry staining of human hypothalamic tissue showed the presence of irisin in the neuronal cells of the paraventricular nucleus, co-localised with neuropeptide Y.

Conclusion: These data suggest a new central role of irisin to potentially influence appetite as well as peripheral energy expenditure which may become desensitised in metabolic disease.