Skeletal muscle NAMPT is induced by exercise in humans.
In mammals, nicotinamide phosphoribosyltransferase (NAMPT) is responsible for the first and rate-limiting step in the conversion of nicotinamide to nicotinamide adenine dinucleotide (NAD+). NAD+ is an obligate cosubstrate for mammalian sirtuin-1 (SIRT1), a deacetylase that activates peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), which in turn can activate mitochondrial biogenesis. Given that mitochondrial biogenesis is activated by exercise, we hypothesized that exercise would increase NAMPT expression, as a potential mechanism leading to increased mitochondrial content in muscle. A cross-sectional analysis of human subjects showed that athletes had about a twofold higher skeletal muscle NAMPT protein expression compared with sedentary obese, nonobese, and type 2 diabetic subjects (P < 0.05). NAMPT protein correlated with mitochondrial content as estimated by complex III protein content (R(2) = 0.28, P < 0.01), MRS-measured maximal ATP synthesis (R(2) = 0.37, P = 0.002), and Vo(2max) (R(2) = 0.63, P < 0.0001). In an exercise intervention study, NAMPT protein increased by 127% in sedentary nonobese subjects after 3 wk of exercise training (P < 0.01). Treatment of primary human myotubes with forskolin, a cAMP signaling pathway activator, resulted in an approximately 2.5-fold increase in NAMPT protein expression, whereas treatment with ionomycin had no effect. Activation of AMPK via AICAR resulted in an approximately 3.4-fold increase in NAMPT mRNA (P < 0.05) as well as modest increases in NAMPT protein (P < 0.05) and mitochondrial content (P < 0.05). These results demonstrate that exercise increases skeletal muscle NAMPT expression and that NAMPT correlates with mitochondrial content. Further studies are necessary to elucidate the pathways regulating NAMPT as well as its downstream effects.
Costford
Sheila R
SR
Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA 70808, USA.
Bajpeyi
Sudip
S
Pasarica
Magdalena
M
Albarado
Diana C
DC
Thomas
Shantele C
SC
Xie
Hui
H
Church
Timothy S
TS
Jubrias
Sharon A
SA
Conley
Kevin E
KE
Smith
Steven R
SR
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D015444:Exercise / Q000502:physiology*; D005081:Exercise Therapy; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008019:Life Style; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology*; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics* / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010807:Physical Endurance / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013177:Sports; D014157:Transcription Factors / Q000378:metabolism; D055815:Young Adult
D016207:Cytokines; D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D014157:Transcription Factors; D005576:Colforsin; D000255:Adenosine Triphosphate; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human