In vivo-determined rates of protein synthesis in gastrocnemius, heart and liver of male and female WT and 4E-BP1/BP2 DKO mice.

<p>Values are means ± SEM; n = 9–12 per group. For all bar graphs, values having a different superscript letter (a versus b) are statistically different (<i>P</i><0.05); values with the same letter are not significantly different. For each tissue, female mice had a smaller sepsis-induced decrease in protein synthesis (<i>P</i><0.05).</p

Sepsis-induced body weight loss in male and female WT and 4E-BP1/BP2 DKO mice.

<p>Values are means ± SEM; n = 9–12 per group. For all bar graphs, values having a different superscript letter (a versus b) are statistically different (<i>P</i><0.05); values with the same letter are not significantly different.</p

Amount of eIF4E•eIF4G complex as well as eIF4B and eEF2 phosphorylation in muscle from male WT and 4E-BP1/BP2 DKO mice under basal and septic conditions.

<p>Bar graphs are means ± SEM; n = 5 male mice per group (panel A) and 8–9 mice per group (panels B and C). For all bar graphs, values having a different superscript letter (a versus b) are statistically different (<i>P</i><0.05); values with the same letter are not significantly different.</p

Sepsis-induced changes in the insulin-like growth factor (IGF)-I mRNA in gastrocnemius from male and female WT and 4E-BP1/BP2 DKO mice.

<p>Values are means ± SEM; n = 9–12 per group. Values are expressed as percent of control normalized for L32, where the male WT control value is arbitrarily set at 100%. For all bar graphs, values having a different superscript letter (a versus b) are statistically different (<i>P</i><0.05); values with the same letter are not significantly different.</p

Body weight and body composition in WT and 4E-BP1/BP2 DKO mice.

<p>Values are means ± SEM; n = 9–12 per group. *<i>P</i><0.05, compared to time-matched WT value. There was a significant (<i>P</i><0.05) increase in all parameters 1 month (m) to 12 months of age, regardless of genotype or sex.</p

Representative Western blots for various proteins important in the control of muscle protein synthesis.

<p>Immunoblots for total and/or phosphorylated AKT, 4E-BP1, 4E-BP2, and S6K1 are presented for both male and female WT and 4E-BP1/BP2 DKO mice. Each lane represents a sample from a different mouse. Western blots were quantitated for male mice only, but data for female mice were qualitatively similar (data not shown). Bar graphs are means ± SEM; n = 8 male mice per group. For all bar graphs, values having a different superscript letter (a versus b) are statistically different (<i>P</i><0.05); values with the same letter are not significantly different. ND  =  not detectable.</p

Sepsis-induced changes in tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNA content in gastrocnemius of in male and female WT and 4E-BP1/BP2 DKO mice.

<p>Values are means ± SEM; n = 9–12 per group. Values for TNFα are expressed as percent of control normalized for L32, where the male WT control value is arbitrarily set at 100%. For IL-6, values are expressed as fold-change above control values which was set at 1.0. For all bar graphs, values having a different superscript letter (a versus b versus c) are statistically different (<i>P</i><0.05); values with the same letter are not significantly different.</p

Indirect calorimetry in WT and 4E-BP1/BP2 DKO mice during the light and dark cycle.

<p>Spontaneous locomotor activity (panel A) was measured using infrared sensor pairs arranged in strips for horizontal (x, y level) and vertical (z level, rearing) activity; respiratory exchange ratio (RER; panel B), oxygen consumption (VO₂; panel C) and heat production (panel D) were assessed by indirect calorimetry over a 24-h period after a 48 h acclimatization period. Values are means ± SEM; n = 9–12 per group. For all bar graphs, values having a different superscript letter (a versus b) are statistically different (<i>P</i><0.05); values with the same letter are not significantly different. While there were no significant differences between WT and DKO for any endpoint assessed, both groups had significantly (<i>P</i><0.05) lower levels of activity, RER, VO₂ and heat production during the light phase compared to the dark phase, but this is not indicated on the figure.</p

Skeletal muscle and heart weights of male and female WT and 4E-BP1/BP2 DKO mice under control and septic conditions.

<p>Values are means ± SEM; n = 9–12 per group. Gastroc = gastrocnemius; Quad = quadriceps. For each tissue, 3-way ANOVA indicated no genotype or sepsis effect, but the absolute weight of each tissue was significantly (<i>P</i><0.05) lower in female compared to male mice. This sex difference was lost when data were normalized to body weight.</p

Sepsis-induced changes in the muscle-specific ubiquitin E3 ligases MuRF1 and atrogin-1 mRNA in gastrocnemius from male and female WT and 4E-BP1/BP2 DKO mice.

<p>Values are means ± SEM; n = 9–12 per group. Values are expressed as percent of control normalized for L32, where the male WT control value is arbitrarily set at 100%. For all bar graphs, values having a different superscript letter (a versus b versus c) are statistically different (<i>P</i><0.05); values with the same letter are not significantly different.</p