科研之友
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摘要
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, CKI alpha 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: alpha 1 and alpha 2. We investigate the circadian rhythm of behavior, physiology and gene expression in AMPK alpha 1-/- and AMPK alpha 2-/- mice. We found that both alpha 1-/- and alpha 2-/- mice are able to maintain a circadian rhythm of activity in dark-dark (DD) cycle, but alpha 1-/- mice have a shorter circadian period whereas alpha 2-/- mice showed a tendency toward a slightly longer circadian period. Furthermore, the circadian rhythm of body temperature was dampened in alpha 1-/- mice, but not in alpha 2-/- mice. The circadian pattern of core clock gene expression was severely disrupted in fat in alpha 1-/- mice, but it was severely disrupted in the heart and skeletal muscle of alpha 2-/- mice. Interestingly, other genes that showed circadian pattern of expression were dysreguated in both alpha 1-/- and alpha 2-/- 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.
- 出版日期2011-3-31
