Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCA215

Poster Communications

The effect of maternal and post-weaning high-fat diet on markers of skeletal muscle insulin-mediated glucose uptake and growth in adult mouse offspring

L. E. Jones1, F. R. Cagampang1, K. Poore1, J. K. Cleal1, P. L. Newland1, L. R. Green1

1. University of Southampton, Southampton, United Kingdom.

Adult obesity is linked to skeletal muscle structure, metabolism and contraction. In the adult female mouse soleus muscle (postural muscle; 37% type I, 63% type II myofibres), the reduction in adult skeletal muscle isometric contraction force by post-weaning (POST) high-fat (HF) diet is minimized by a prior exposure of their mothers to a pregnancy and lactation (PRE) HF diet (1). The POST HF diet was also associated with reduced soleus muscle GLUT-4 and insulin receptor (InsR) mRNA levels (2), which may mediate in part the glucose intolerance previously observed in this model (2) and be linked to muscle contractile capacity. However, muscles are heterogeneous in fibre structure and function, for example, the extensor digitorum longus (EDL) muscle is 96% type II myofibres and is involved in dorsiflexion and extension of the foot and toes. Therefore in this study we determined the expression of GLUT-4 and InsR (markers of insulin-mediated glucose uptake), and Akt-1 (marker of muscle fibre growth and inhibitor of apoptosis) in the EDL muscle. Female C57BL/6J mice were fed a control (C; 7% kcal fat) or high fat (HF; 45% kcal fat) diet 6 weeks prior to mating and throughout lactation (PRE). Offspring were weaned (POST) onto the same C or HF diet creating 4 different diet groups: C/C, C/HF, HF/C and HF/HF (n=6-8 per group). Female 30 week offspring EDL muscle GLUT-4, InsR, and Akt-1 mRNA levels were measured by RT-qPCR. Data are mean relative gene expression ± SEM and were analysed by 2-way ANOVA. Female offspring EDL muscle GLUT-4 mRNA levels were reduced in POST HF mice regardless of PRE diet (C/HF+HF/HF, 0.95±0.02 vs. C/C+HF/C, 1.14±0.04; p<0.001). There was no significant difference in InsR mRNA levels between groups. Akt-1 mRNA levels were higher in POST HF mice regardless of PRE diet (C/HF+HF/HF, 1.00±0.03 vs. C/C+HF/C, 0.86±0.03; p<0.01). Our finding of lower GLUT-4 mRNA in POST HF diet group EDL muscle is similar to previous observations in the soleus muscle (2) and may contribute to the glucose intolerance in these animals. Unlike the soleus muscle, InsR mRNA levels in EDL muscle were unaltered by diet, highlighting muscle bed heterogeneity in the insulin-mediated glucose uptake pathway. Increased Akt-1 mRNA levels in POST HF EDL muscle suggests an alteration in muscle growth which could impact on whole body glucose homeostasis and muscle contraction in these animals.

Where applicable, experiments conform with Society ethical requirements