Short-term rapamycin treatment in mice has few effects on the transcriptome of white adipose tissue compared to

Wilson C Fok1, Carolina Livi2, Alex Bokov3

  • 1Department of Internal Medicine, Division of Hematology, Washington University in St. Louis, St. Louis, MO 63110, USA.

Insights

Dietary restriction (DR) significantly alters gene expression in mouse adipose tissue, unlike the drug rapamycin. This suggests that DR and rapamycin extend lifespan through distinct biological pathways.

Area of Science:

  • Aging research
  • Molecular biology
  • Metabolism

Background:

  • Rapamycin inhibits the target of rapamycin (TOR) pathway, impacting cell growth and energy.
  • Rapamycin and dietary restriction (DR) are hypothesized to extend lifespan via similar mechanisms.
  • Investigating the molecular effects of rapamycin and DR on adipose tissue is crucial for understanding aging.

Purpose of the Study:

  • To compare the transcriptomic effects of rapamycin and DR in mouse white adipose tissue.
  • To determine if rapamycin and DR influence lifespan through shared or distinct molecular pathways.

Main Methods:

  • Microarray analysis of white adipose tissue from mice treated with rapamycin or DR for 6 months.
  • Multidimensional scaling and heatmap analyses to assess transcriptomic changes.
  • Ingenuity pathway analysis to identify significantly altered biological pathways.

Main Results:

  • Rapamycin had minimal impact on the transcriptome, altering only six transcripts.
  • DR significantly altered over 1000 transcripts in the adipose tissue.
  • DR significantly impacted stearate biosynthesis and circadian rhythm signaling pathways.

Conclusions:

  • Dietary restriction, but not rapamycin, significantly affects the adipose tissue transcriptome.
  • These findings suggest that rapamycin and DR extend lifespan through different molecular mechanisms and pathways.