![]() Labels: MiParea: Respiration, mt-Biogenesis mt-density, Exercise physiology nutrition life style O2k-Network Lab: US FL Orlando Sparks LM.improved biochemical coupling efficiency) and an increased capacity to burn CI&FAO-linked substrates indicate a synergistic improvement in muscle mitochondrial function via NAMPT and endurance exercise, whereby an increased amount of NAMPT is sufficient to enhance the exercise-induced improvements in substrate metabolism. Taken together, decreased LEAK/OXPHOS ratios (i.e. While training improved coupling efficiency in the WT mice ( P<0.05, Figure 1B), it tended to further improve coupling efficiency in the NamptTg mice as well ( P=0.107 Fig. Increased NAMPT levels were sufficient to dramatically improve mitochondrial coupling efficiency, as reflected by the significant reduction in the ratio of proton leak-linked respiration ( L) to OXPHOS capacity ( P) in the NamptTg mice compared with WT mice at baseline ( P<0.05 Figure 1B). Notably, this training-induced improvement in the NamptTg mice tended to be higher than the trivial increase in CI&FAO flux with training in WT mice ( P=0.0595 Fig. NamptTg mice had an increased CI&FAO capacity after training ( P<0.05 Fig. SUIT protocols were performed in permeabilized fiber bundles using either Complex I-linked substrates (CI, pyruvate+glutamate+malate) or a fatty acid oxidation (FAO, palmitoyl-carnitine+malate) plus CI–linked (glutamate) substrate combination (CI&FAO Fig. Quadriceps muscles were used for the respiration measurements. Mice were fasted for 5 h prior to sacrifice. No differences were observed in the proclivity of NamptTg mice to engage in voluntary exercise. WT and NamptTg mice were housed with ('trained') or without ('sedentary') running wheels to elicit voluntary exercise for a period of 7 weeks (WT Sedentary WT Trained NamptTg Sedentary NamptTg Trained). A concomitant elevation of NMN (5-fold) and NAD + (3-fold) in NamptTg skeletal muscle revealed increased NAMPT enzymatic activity. We hypothesized that muscle-specific overexpression of NAMPT in mice ( NamptTg) would improve muscle respiratory capacity and control and would be additive with endurance exercise training in these mice.īased on western blotting studies, NamptTg mice express 10-fold more skeletal muscle NAMPT protein compared to wild type (WT) mice. The mechanisms responsible for metabolic adaption are unclear. Caloric restriction-induced beneficial effects in oxidative stress, mitochondrial biogenesis and metabolic adaptation in mice require NAMPT. We previously showed that exercise increased skeletal muscle NAMPT expression, which correlates with mitochondrial content in humans. In mammals, nicotinamide phosphoribosyltransferase (NAMPT) is responsible for the first and rate-limiting step in the “salvage pathway” that converts nicotinamide to nicotinamide adenine dinucleotide (NAD +). Sparks LM, Stephens NA, Gabriel M, Gardell SJ, Smith SR (2014) Mitochondr Physiol Network 19.13 - MiP2014
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