Skeletal muscle overexpression of nicotinamide phosphoribosyl transferase in mice coupled with voluntary exercise augments exercise endurance.
| Autor: | Costford SR; Sanford-Burnham-Prebys Medical Discovery Institute, Orlando, FL, USA; Pennington Biomedical Research Center, Baton Rouge, LA, USA., Brouwers B; Translational Research Institute for Metabolism and Diabetes, Orlando, FL, USA., Hopf ME; Sanford-Burnham-Prebys Medical Discovery Institute, Orlando, FL, USA., Sparks LM; Sanford-Burnham-Prebys Medical Discovery Institute, Orlando, FL, USA; Translational Research Institute for Metabolism and Diabetes, Orlando, FL, USA., Dispagna M; Sanford-Burnham-Prebys Medical Discovery Institute, Orlando, FL, USA., Gomes AP; Harvard Medical School, Boston, MA, USA., Cornnell HH; Translational Research Institute for Metabolism and Diabetes, Orlando, FL, USA., Petucci C; Sanford-Burnham-Prebys Medical Discovery Institute, Orlando, FL, USA., Phelan P; Sanford-Burnham-Prebys Medical Discovery Institute, Orlando, FL, USA., Xie H; Pennington Biomedical Research Center, Baton Rouge, LA, USA; Translational Research Institute for Metabolism and Diabetes, Orlando, FL, USA., Yi F; Translational Research Institute for Metabolism and Diabetes, Orlando, FL, USA., Walter GA; University of Florida, Gainesville, FL, USA., Osborne TF; Sanford-Burnham-Prebys Medical Discovery Institute, Orlando, FL, USA., Sinclair DA; Harvard Medical School, Boston, MA, USA., Mynatt RL; Pennington Biomedical Research Center, Baton Rouge, LA, USA., Ayala JE; Sanford-Burnham-Prebys Medical Discovery Institute, Orlando, FL, USA., Gardell SJ; Sanford-Burnham-Prebys Medical Discovery Institute, Orlando, FL, USA., Smith SR; Sanford-Burnham-Prebys Medical Discovery Institute, Orlando, FL, USA; Pennington Biomedical Research Center, Baton Rouge, LA, USA; Translational Research Institute for Metabolism and Diabetes, Orlando, FL, USA. Electronic address: Steven.R.Smith.MD@flhosp.org. |
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| Jazyk: | angličtina |
| Zdroj: | Molecular metabolism [Mol Metab] 2018 Jan; Vol. 7, pp. 1-11. Date of Electronic Publication: 2017 Nov 06. |
| DOI: | 10.1016/j.molmet.2017.10.012 |
| Abstrakt: | Objective: Nicotinamide phosphoribosyl transferase (NAMPT) is the rate-limiting enzyme in the salvage pathway that produces nicotinamide adenine dinucleotide (NAD + ), an essential co-substrate regulating a myriad of signaling pathways. We produced a mouse that overexpressed NAMPT in skeletal muscle (NamptTg) and hypothesized that NamptTg mice would have increased oxidative capacity, endurance performance, and mitochondrial gene expression, and would be rescued from metabolic abnormalities that developed with high fat diet (HFD) feeding. Methods: Insulin sensitivity (hyperinsulinemic-euglycemic clamp) was assessed in NamptTg and WT mice fed very high fat diet (VHFD, 60% by kcal) or chow diet (CD). The aerobic capacity (VO Results: NAMPT enzyme activity in skeletal muscle was 7-fold higher in NamptTg mice versus WT mice. There was a concomitant 1.6-fold elevation of skeletal muscle NAD + . NamptTg mice fed VHFD were partially protected against body weight gain, but not against insulin resistance. Notably, voluntary exercise training elicited a 3-fold higher exercise endurance in NamptTg versus WT mice. Mitochondrial gene expression was higher in NamptTg mice compared to WT mice, especially when fed HFD. Mitochondrial gene expression was higher in exercised NamptTg mice than in sedentary WT mice. Conclusions: Our studies have unveiled a fascinating interaction between elevated NAMPT activity in skeletal muscle and voluntary exercise that was manifest as a striking improvement in exercise endurance. (Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.) |
| Databáze: | MEDLINE |
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