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

Subhash D. Katewa, Fabio Demontis, Marysia Kolipinski, Alan Hubbard, Matthew S. Gill, Norbert Perrimon, Simon Melov, Pankaj Kapahi

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)97-103
Number of pages7
JournalCell Metabolism
Volume16
Issue number1
DOIs
StatePublished - Jul 3 2012
Externally publishedYes

Bibliographical note

Funding Information:
We thank Roger Chang, Akio Nada, Emily Chang (life-span data collection), Krysta Felkey (microarrays) and Vishal Patel (staining and quantification). We also thank John Tower, Haig Keshishian, and Kai Zinn for providing various Gal4 drivers used in the study. We thank Matthew Laye, Gordon Lithgow, Judith Campisi, Martin Brand, and members of the Kapahi Lab for helpful discussions and suggestions. This work was funded by grants from the AFAR and the NIH (R01 AG031337-01A1; RO1 AG038688; RL1 AAG032113 and P01 AG025901-S1) (P.K.), RL9 AG032114 (S.D.K.), R01 AG036992 (M.S.G), a Nathan Shock Award (P30AG025708) (S.M.) and R01 AR057352 (N.P.). F.D. is an EMF/AFAR postdoctoral fellow. N.P. is an HHMI investigator.

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