Acute Dietary Restriction Restores Myofiber Growth Following Mechanical Overload in HFpEF
(A) Experimental design schematic showing start and endpoints of caloric restriction (CR) and mechanical overload of the EDL. (B) Representative images of contralateral (CL) and overloaded (OL) EDL muscles stained for Type I (red), Type IIa (green), and Type IIb/IIx (unstained/black) fibers and capillaries (bright green). (C) Total FCSA, (D) Type I FCSA, (E) Type II FCSA, (F) Type IIb/IIx FCSA, and (G) fiber type distribution of CL (CON n = 4, HFpEF n = 4, HFpEF+CR n = 4) and OL (CON n = 4, HFpEF n = 4, HFpEF+CR n = 4) EDL muscles. (H) Soleus contractile power measured across various percentages of maximal force (CON n = 4, HFpEF n = 4, HFpEF+CR n = 4). (I) EDL protein expression of puromycin, 4E-BP1, p-4E-BP1, S6, p-S6, AMPK, p-AMPK, and p62 in OL and CL muscles (CON n = 4, HFpEF n = 4, HFpEF+CR n = 4) and (J) gene expression for IGF1 (CON n = 4, HFpEF n = 4, HFpEF+CR n = 4). (K) Protein contents of 4E-BP1, p-4E-BP1, S6, p-S6, AMPK, and p-AMPK in stimulated (ST) and nonstimulated (NST) soleus. Gene expression of (L) MuRF1, (M) MAFbx, and (N) myostatin in CL and OL EDL muscles (CON n = 4, HFpEF n = 4, HFpEF+CR n = 4). Differences were assessed by 2-way analysis of variance followed by Bonferroni post hoc test. Data are presented as mean ± SD, and the level of significance was accepted as ∗P < 0.05; ∗∗P < 0.01; and ∗∗∗P < 0.001 for all analyses. Abbreviations as in Figure 1.