Gain-of-Function R225W Mutation in Human AMPKγ3 Causing Increased Glycogen and Decreased Triglyceride in Skeletal Muscle
2007

Mutation in AMPKγ3 Increases Glycogen and Decreases Triglyceride in Muscle

Sample size: 1520 publication 10 minutes Evidence: moderate

Author Information

Author(s): Sheila R. Costford, Nihan Kavaslar, Nadav Ahituv, Shehla N. Chaudhry, Wendy S. Schackwitz, Robert Dent, Len A. Pennacchio, Ruth McPherson, Mary-Ellen Harper

Primary Institution: University of Ottawa

Hypothesis

Does the R225W mutation in the AMPKγ3 subunit affect energy metabolism in human skeletal muscle?

Conclusion

The R225W mutation in AMPKγ3 leads to increased muscle glycogen content and decreased intramuscular triglyceride levels.

Supporting Evidence

  • The R225W mutation was found in two unrelated families.
  • Carriers of the mutation showed a 90% increase in muscle glycogen content.
  • AMPK activity was approximately doubled in muscle cells from R225W carriers.

Takeaway

A change in a gene related to energy use in muscles can help muscles store more sugar and less fat.

Methodology

The study involved sequencing the AMPK γ3 gene in obese and lean individuals and analyzing muscle biopsies for AMPK activity, glycogen, and triglyceride content.

Potential Biases

Potential selection bias in participant recruitment from specific clinics.

Limitations

The study had a small sample size for muscle biopsies and did not assess long-term metabolic responses.

Participant Demographics

761 obese and 759 lean Caucasian individuals, mean age around 40 years.

Statistical Information

P-Value

p=0.002 for glycogen content, p=0.032 for IMTG content

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0000903

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