Protein synthesis in skeletal muscle is markedly stimulated (approximately 180% of control rate) within 3 h of oral feeding in 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 or nutrients) nor the mechanisms responsible for the effect of feeding are well understood. Results of the present study revealed that the amount of
eukaryotic initiation factor 4E (eIF-4E) present in the phosphorylated form (i.e., 70%) was not changed after overnight
starvation or a subsequent 3-h refeeding period compared with muscles from freely fed mice. In contrast, the phosphorylation state of the
eIF-4E binding protein 1 (4E-BP1) was changed with nutritional state.
Starvation increased the proportion of the unphosphorylated form of 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 threefold, indicative of an increase in the eIF-4E.4E-BP1 complex. The increased association of 4E-BP1 with
eIF-4E was completely reversed within 3 h 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.