AMPKed up

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The paper:
S. Jäger et al., “AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha,” Proc Natl Acad Sci, 104(29):12017–22, 2007. (Cited in 106 papers)

The finding:
AMP-activated kinase (AMPK) plays a major role in the regulation of cellular metabolism, increasing gene expression in a variety of metabolic pathways when a cell is energy-deprived, but how it causes these changes was unclear. One target gene, peroxisome-proliferator-activated receptor Υ coactivator 1α (PGC-1α), is another key player in metabolism. By injecting AMPK activators into mice with and without PGC-1α in their skeletal muscle cells (but carrying PGC-1α in other cell types), cellular biochemist Bruce Spiegelman of Harvard Medical School and his colleagues demonstrated that AMPK directly activates PGC-1α —which in turn mediates AMPK’s effects.

The mechanism:
Using mass spectrometry analysis, Spiegelman and his...

The concern:
To date, there have been no follow-up studies confirming these findings or demonstrating their relevance during normal metabolism and energy depletion, says Thomson. “That’s surprising to me,” he says.

The next step:
Spiegelman’s lab is currently investigating whether this mechanism of PGC-1α activation holds true in other parts of the body. “We have no reason to think it’s specific for muscle,” Spiegelman says.

Genes regulated by AMPK activation of PGC-1α:
GLUT4, PGC-1α, cytochrome c, UCP-1, UCP-3

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