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[Preprint]. 2025 Jan 21:2024.03.28.586997. Originally published 2024 Mar 31. [Version 2] doi: 10.1101/2024.03.28.586997

Figure 1 – GR-R24K mice are protected from diet-induced obesity, insulin resistance and weakness.

Figure 1 –

(A-C) Compared to WT littermates, R24K-homozygous mice showed leaner body composition with normal and high-fat (60% kcal) diets. (D-E) The genetic variant increased aerobic capacity (treadmill work until exhaustion) and muscle force (hindlimb dorsiflexor assay) in normal diet, rescuing those parameters after high-fat diet feeding. (F-G) R24K-homozygous mice showed increased or rescued insulin sensitivity, as shown by increased glucose infusion rates (GIRs) during a hyperinsulinemic-euglycemic clamp and HOMA-IR values at endpoint of diet regimens. (H) Muscle insulin sensitivity and glucose uptake were increased by the R24K variant, as shown by muscle 2DG uptake at the end of the hyperinsulinemic-euglycemic clamp. (I) R24K-homozygous mice showed reduced or rescued glycemia in the fed state (ZT0, after feeding during the active phase). n=3–7♂/group; diet exposures for 12 weeks from 4mo to 7mo; 2w ANOVA + Sidak: ns, non significant; *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001.