Skeletal muscle overexpression of nicotinamide phosphoribosyl transferase in mice coupled with voluntary exercise augments exercise endurance

DSpace/Manakin Repository

Skeletal muscle overexpression of nicotinamide phosphoribosyl transferase in mice coupled with voluntary exercise augments exercise endurance

Citable link to this page

 

 
Title: Skeletal muscle overexpression of nicotinamide phosphoribosyl transferase in mice coupled with voluntary exercise augments exercise endurance
Author: Costford, Sheila R.; Brouwers, Bram; Hopf, Meghan E.; Sparks, Lauren M.; Dispagna, Mauro; Gomes, Ana P.; Cornnell, Heather H.; Petucci, Chris; Phelan, Peter; Xie, Hui; Yi, Fanchao; Walter, Glenn A.; Osborne, Timothy F.; Sinclair, David A.; Mynatt, Randall L.; Ayala, Julio E.; Gardell, Stephen J.; Smith, Steven R.

Note: Order does not necessarily reflect citation order of authors.

Citation: Costford, S. R., B. Brouwers, M. E. Hopf, L. M. Sparks, M. Dispagna, A. P. Gomes, H. H. Cornnell, et al. 2017. “Skeletal muscle overexpression of nicotinamide phosphoribosyl transferase in mice coupled with voluntary exercise augments exercise endurance.” Molecular Metabolism 7 (1): 1-11. doi:10.1016/j.molmet.2017.10.012. http://dx.doi.org/10.1016/j.molmet.2017.10.012.
Full Text & Related Files:
Abstract: 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 (VO2max) and endurance performance of NamptTg and WT mice before and after 7 weeks of voluntary exercise training (running wheel in home cage) or sedentary conditions (no running wheel) were measured. Skeletal muscle mitochondrial gene expression was also measured in exercised and sedentary mice and in mice fed HFD (45% by kcal) or low fat diet (LFD, 10% by kcal). 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.
Published Version: doi:10.1016/j.molmet.2017.10.012
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784330/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34868824
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters