Postprandial stimulation of muscle protein synthesis is mediated
through translation initiation and is independent of changes in
insulin.
Svanberg, Elisabeth, Leonard S. Jefferson, Kent Lundholm, and Scot R.
Kimball.
Department of Surgery, Sahlgrenska University Hospital, University
of Goteborg, S-413 45 Goteborg, Sweden, Department of Cellular and
Molecular Physiology, Pennsylvania State University, College of
Medicine, Hershey, PA 17033
APStracts 4:0030E, 1997.
Protein synthesis in skeletal muscle is markedly stimulated
(approximately 180% of control rate) within three hours of oral
feeding of mice subjected to an overnight fast (18 h). The
stimulation of protein synthesis is the result of a faster rate of
translation initiation; however, neither the mediators (i.e.
hormones/nutrients) nor the mechanisms responsible for the effect of
feeding are well understood. Results of the present study revealed
that the amount of eIF-4E present in the phosphorylated form (i.e.
70%) was not changed following overnight starvation, or a subsequent
3 h refeeding period compared to muscles from freely fed mice. In
contrast, the phosphorylation state of 4E-BP1 was changed with
nutritional state. Starvation increased the proportion of the
unphosphorylated form of the eIF-4E binding protein, 4E-BP1, whereas
feeding promoted a shift to the more highly phosphorylated forms of
the protein. Moreover, starvation increased the amount of 4E-BP1
recovered by almost three-fold, indicative of an increase in the eIF
-4E[beta]4E-BP1 complex. The increased association of 4E-BP1 with eIF
-4E was completely reversed within three hours of feeding. Starvation
and refeeding also altered the amount of eIF-4G that
coimmunoprecipitated with eIF-4E. However, in contrast to the results
obtained for 4E-BP1, starvation decreased the amount of eIF-4G
recovered in the eIF-4E immunoprecipitate, suggesting that starvation
causes a decrease in the formation of the active eIF-4F complex. The
alterations in 4E-BP1 phosphorylation and association of 4E-BP1 and
eIF-4G with eIF-4E observed in control mice in response to starvation
and refeeding were also observed in diabetic mice exhibiting
characteristics of type I or type II diabetes subjected to the same
conditions, suggesting that insulin alone does not mediate the
observed changes. Thus, the integrated feeding response represents an
important area of investigation for understanding the regulation of
translation initiation.
Received 30 October 1996; accepted in final form 23 January 1997.
APS Manuscript Number E543-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 19 February 1997