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This Article Full Text Full Text (PDF) All Versions of this Article: 586/9/2371    most recent jphysiol.2008.150987v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Costello, P. M. Articles by Green, L. R. Search for Related Content PubMed PubMed Citation Articles by Costello, P. M. Articles by Green, L. R. Related Collections Skeletal Muscle and Exercise

¹ Institute of Developmental Sciences, Developmental Origins of Health and Disease Division, University of Southampton, Southampton SO16 6YD, UK
² Centre for Applied Biomedical Research, King's College London, London, UK
³ MRC Epidemiology Resource Centre, Southampton General Hospital, Southampton, UK

Poor prenatal nutrition is associated with a greater risk of adult glucose intolerance and insulin insensitivity in the offspring. Skeletal muscle is the primary tissue for glucose utilization, and insulin resistance in muscle is the earliest identifiable abnormality in the pre-diabetic patient. We investigated the effect of early and late gestation undernutrition on structure and markers of growth and glucose metabolism regulation in the fetal triceps brachii (TB, slow- and fast-twitch myofibres) and soleus (slow-twitch myofibres) muscles. Pregnant sheep were fed 100% nutrient requirements (C, n = 8) or a restricted diet peri-implantation (PI, n = 9; 40%, 1–31 days gestation (dGA) (term 147)) or in late gestation (L, n = 6; 50%, 104–127 dGA). At 127 ± 1 dGA we measured myofibre and capillary density in the fetal TB and soleus muscles, and mRNA levels in the TB of insulin receptor (InsR), glucose transporter-4 (GLUT-4) and type 1 insulin-like growth factor receptor (IGF-1R). Total myofibre and capillary densities were lower in the TB, but not the soleus, of PI and L fetuses. The predominant effect in the L group was on slow-twitch myofibres. In TB, InsR, GLUT-4 and IGF-1R mRNA levels were greater in L group fetuses. Our finding of reduced myofibre density is consistent with a redistribution of resources at the expense of specific peripheral tissues by early and late gestation undernutrition which may be mediated by a decrease in capillary density. The increase in key regulatory components of glucose uptake following late gestation undernutrition may constitute a short-term compensation to maintain glucose homeostasis in the face of fewer type I (insulin-sensitive) myofibres. However, together these adaptations may influence the risk of later metabolic disease and thus our findings have implications for future strategies aimed at improving maternal diet.

(Received 10 January 2008; accepted after revision 6 March 2008; first published online 13 March 2008)
Corresponding author L. R. Green: Institute of Developmental Sciences, Developmental Origins of Health and Disease Division, MP 887, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. Email: lgreen{at}soton.ac.uk