| First Author | Um JH | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 3 | Pages | e18450 |
| PubMed ID | 21483791 | Mgi Jnum | J:171657 |
| Mgi Id | MGI:4950763 | Doi | 10.1371/journal.pone.0018450 |
| Citation | Um JH, et al. (2011) AMPK Regulates Circadian Rhythms in a Tissue- and Isoform-Specific Manner. PLoS One 6(3):e18450 |
| abstractText | BACKGROUND: AMP protein kinase (AMPK) plays an important role in food intake and energy metabolism, which are synchronized to the light-dark cycle. In vitro, AMPK affects the circadian rhythm by regulating at least two clock components, CKIalpha and CRY1, via direct phosphorylation. However, it is not known whether the catalytic activity of AMPK actually regulates circadian rhythm in vivo. METHODOLOGY/PRINCIPAL FINDING: THE CATALYTIC SUBUNIT OF AMPK HAS TWO ISOFORMS: alpha1 and alpha2. We investigate the circadian rhythm of behavior, physiology and gene expression in AMPKalpha1-/- and AMPKalpha2-/- mice. We found that both alpha1-/- and alpha2-/- mice are able to maintain a circadian rhythm of activity in dark-dark (DD) cycle, but alpha1-/- mice have a shorter circadian period whereas alpha2-/- mice showed a tendency toward a slightly longer circadian period. Furthermore, the circadian rhythm of body temperature was dampened in alpha1-/- mice, but not in alpha2-/- mice. The circadian pattern of core clock gene expression was severely disrupted in fat in alpha1-/- mice, but it was severely disrupted in the heart and skeletal muscle of alpha2-/- mice. Interestingly, other genes that showed circadian pattern of expression were dysreguated in both alpha1-/- and alpha2-/- mice. The circadian rhythm of nicotinamide phosphoryl-transferase (NAMPT) activity, which converts nicotinamide (NAM) to NAD(+), is an important regulator of the circadian clock. We found that the NAMPT rhythm was absent in AMPK-deficient tissues and cells. CONCLUSION/SIGNIFICANCE: This study demonstrates that the catalytic activity of AMPK regulates circadian rhythm of behavior, energy metabolism and gene expression in isoform- and tissue-specific manners. |
