Proceedings of The Physiological Society

Obesity (2014) Proc Physiol Soc 32, PC053

Poster Communications

Differential changes in gene expression for FNDC5 during postnatal development are not associated with any change in plasma irisin concentration in sheep

M. Pope1, M. Birtwistle1, G. Davies1, V. Perry1, H. Budge1, M. Symonds1

1. University of Nottingham, Nottingham, United Kingdom.


Background and Aims: Irisin, a circulatory peptide derived from the FNDC5 gene, has been proposed as an exercise-induced myokine that influences brown adipose tissue (BAT) thermogenesis [1]. It has also been suggested to be released when stimulated by cold exposure in adult humans [2]. In the new-born sheep there is a transition from nonshivering thermogenesis in BAT to shivering in skeletal muscle [3] to mitigate effective adaptation to the cold exposure of the extra-uterine environment. The aim of the present study was to examine whether this adaptation was accompanied with changes in gene expression for FNDC5 within BAT and skeletal muscle or changes in the plasma concentration of irisin.Methods: Four triplet-bearing mothers were entered into the study and a randomly selected triplet was blood sampled from the jugular vein and then euthanased with an intra-venous injection (Pentobarbital Sodium, 200mg/kg body weight) at 1, 7 or 28 days of age for tissue sampling (n=4 per time point) under Home Office Approval, UK. Adipose tissue was sampled from the sternal/clavicular region and skeletal muscle from the triceps brachii .Samples were weighed and stored at -80°C. The RNA was extracted and gene expression analysed by qRT-PCR. Relative mRNA expression was calculated using the GeNorm method corrected to the geometric mean of reference genes 18S and RPL19, and expressed in arbitrary units. Plasma irisin was determined after each sample was diluted 1:20 using the Phoenix Pharmaceuticals kit No. EK-067-29. Data are presented as mean ± SEM and unpaired t-Test used for comparisons with age.Results: The FCDN5 gene was equally abundant in both BAT and skeletal muscle at 1 day of age. There was then a divergent change in gene expression with age, with a gradual decline in sternal fat, compared with a pronounced increased at 7 days in skeletal muscle followed by a large decrease up to 28 days of age (7 day - 0.8616±0.05305, (n=4), 28 day 0.2548±0.01412 (n=4); P<0.0001). In contrast there was no change in plasma irisin with age (7 day - 116.5±6.812 (n=4), 28 day - 129.1±11.23 (n=4)).Conclusions: The increase in FCND5 at one week of age is coincident with the increased recruitment of shivering thermogenesis as the dominant response to acute cold exposure. This was not accompanied with any change in plasma irisin thereby adding to more recent evidence that its release into the circulation is not linked to tissue changes in FCDN5 [3]. The lack of any change in irisin with age further suggests no direct role in thermal adaptation after birth.

Where applicable, experiments conform with Society ethical requirements