![]() The insulin-like growth factor 2 (IGF2) mRNA binding proteins (IGF2BPs or IMP1 to -3) participate in the splicing, transport, translation, and stabilization of a wide variety of RNAs in a transcript- and tissue-specific manner ( 1). The greater dependence on muscle glucose metabolism during increased oxygen demand may promote central fatigue and thereby diminish voluntary activity. IMP2-deficient muscle fibers treated with a mitochondrial uncoupler to increase electron flux, as occurs with exercise, exhibit reduced oxygen consumption from fatty acids, with higher oxygen consumption from glucose. ![]() IMP2-deficient muscle exhibits reduced fatty acid oxidation, due to a reduced abundance of mRNA of peroxisome proliferator-activated receptor α (PPARα), an IMP2 client, and PPARα protein. The diet-dependent reduction in voluntary exercise is likely due to altered muscle metabolism, as contractile function is normal. Protein synthesis is reduced despite unaltered mTOR complex 1 activity. Gsk3α is disinhibited, and S536-phosphorylated ε subunit of eukaryotic initiation factor 2B is hyperphosphorylated. The reduced fiber size of IMP2-deficient muscle is attributable, in part, to diminished autocrine Igf2 production basal tyrosine phosphorylation of the insulin and IGF1 receptors is diminished, and Akt1 activation is selectively reduced. The two phenotypes are due to altered output from different IMP2 client mRNAs. ![]() Reduced wheel running occurs when mice are fed a high-fat diet but is normalized when mice consume standard chow. Insulin-like growth factor 2 (IGF2) mRNA binding protein 2 (IMP2) was selectively deleted from adult mouse muscle two phenotypes were observed: decreased accrual of skeletal muscle mass after weaning and reduced wheel-running activity but normal forced treadmill performance. ![]()
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