Fig 1: FNIP2 and LAMP2 immuno-localization on skeletal muscle biopsies. (A) FNIP2/CY3 expression was continuous and intense at the level of the sarcolemma membranes, and in the sarcoplasmic vacuoles and microvacuoles in FNIP2 [p.S551R] mutated biopsies, while more or less extended irregularly shaped spots of positive signals appeared at the edge in some fibres in (p.S301P) mutated biopsies. The LAMP2/FITC reaction was quite superimposable to that of FNIP2 in these biopsies. (B) A faint and diffuse FNIP2/CY3 positive reaction was observed at the sarcolemma and sarcoplasm of muscle fibres in both the wild type individuals and external controls (CNT1, CNT2). Nuclei were counterstained with DAPI (blue). Scale bar: 200 μm.
Fig 2: Deletion of muscle FNIP1 enhances exercise capacity in mice.(A) Representative immunoblotting analysis of FNIP1 and FNIP2 expression in tissue from indicated mice. n = 4 to 5 mice per group. (B) Exercise endurance test in FNIP1 mKO mice. Left: A schematic depicting increments of speed over time. Middle and right: Bars represent the running time and distance for 8-week-old male mice on a motorized treadmill. n = 11 mice per group. (C and D) Exercise capacity test in FNIP1 mKO mice. (C) The schematic depicts increments of speed over time. (D) The RER in FNIP1 mKO mice. n = 7 mice per group. (E) Maximal speed and total running distance in FNIP1 mKO mice. n = 7 mice per group. (F) VO2 (oxygen consumption) during exercise. The gray-shaded area under the VO2 line illustrates the difference in speed to exhaustion in FNIP1 mKO mice compared to WT controls. n = 7 mice per group. (G) Peak VO2 during exercise in FNIP1 mKO mice. n = 6 to 7 mice per group. (H) Blood lactate levels in indicated mice after a 25-min exercise. n = 11 mice per group. (I to L) Blood glucose (I), TG (J), NEFA (K), and β-hydroxybutyrate (β-HB) (L) levels were determined in indicated mice at rest (Sed) or after 150-min exercise (Ex150). n = 4 to 5 mice per group. (M) Representative electron micrographs of soleus muscle showing mitochondria in sections from indicated mice. n = 3 mice per group. Scale bars, 5.0 μm. Error bars are shown as the means ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001. The P value was determined by Student’s t test [(B), (D), (E), (G), and (H)] or one-way ANOVA coupled to Fisher’s LSD post hoc test [(I) to (L)].
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