Intramyocellular fatty-acid metabolism plays a critical role in mediating responses to dietary restriction in Drosophila melanogaster

Cell Metab. 2012 Jul 3;16(1):97-103. doi: 10.1016/j.cmet.2012.06.005.


Changes in fat content have been associated with dietary restriction (DR), but whether they play a causal role in mediating various responses to DR remains unknown. We demonstrate that upon DR, Drosophila melanogaster shift their metabolism toward increasing fatty-acid synthesis and breakdown, which is required for various responses to DR. Inhibition of fatty-acid synthesis or oxidation genes specifically in the muscle tissue inhibited life-span extension upon DR. Furthermore, DR enhances spontaneous activity of flies, which was found to be dependent on the enhanced fatty-acid metabolism. This increase in activity was found to be at least partially required for the life-span extension upon DR. Overexpression of adipokinetic hormone (dAKH), the functional ortholog of glucagon, enhances fat metabolism, spontaneous activity, and life span. Together, these results suggest that enhanced fat metabolism in the muscle and physical activity play a key role in the protective effects of DR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA Carboxylase / genetics
  • Acetyl-CoA Carboxylase / metabolism
  • Animals
  • Caloric Restriction*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / metabolism*
  • Drosophila melanogaster / physiology
  • Fat Body / metabolism*
  • Fatty Acids / metabolism*
  • Female
  • Gene Expression
  • Gene Knockdown Techniques
  • Insect Hormones / genetics
  • Insect Hormones / metabolism
  • Lipogenesis
  • Lipolysis
  • Longevity
  • Male
  • Motor Activity
  • Muscle Cells / metabolism*
  • Muscles / cytology
  • Muscles / metabolism
  • Oligopeptides / genetics
  • Oligopeptides / metabolism
  • Pyrrolidonecarboxylic Acid / analogs & derivatives
  • Pyrrolidonecarboxylic Acid / metabolism
  • RNA Interference
  • Triglycerides / metabolism


  • Drosophila Proteins
  • Fatty Acids
  • Insect Hormones
  • Oligopeptides
  • Triglycerides
  • DAKH peptide
  • Acetyl-CoA Carboxylase
  • Pyrrolidonecarboxylic Acid