Systemic lipolysis promotes physiological fitness in Drosophila melanogaster

Linshan Shang, Elizabeth Aughey, Huiseon Kim, Timothy D. Heden, Lu Wang, Charles P. Najt, Nicholas Esch, Sophia Brunko, Juan E. Abrahante, Marissa Macchietto, Mara T. Mashek, Todd Fairbanks, Daniel E.L. Promislow, Thomas P. Neufeld, Douglas G. Mashek

Research output: Contribution to journalArticlepeer-review

Abstract

Since interventions such as caloric restriction or fasting robustly promote lipid catabolism and improve aging-related phenotypical markers, we investigated the direct effect of increased lipid catabolism via overexpression of bmm (brummer, FBgn0036449), the major triglyceride hydrolase in Drosophila, on lifespan and physiological fitness. Comprehensive characterization was carried out using RNA-seq, lipidomics and metabolomics analysis. Global overexpression of bmm strongly promoted numerous markers of physiological fitness, including increased female fecundity, fertility maintenance, preserved locomotion activity, increased mitochondrial biogenesis and oxidative metabolism. Increased bmm robustly upregulated the heat shock protein 70 (Hsp70) family of proteins, which equipped the flies with higher resistance to heat, cold, and ER stress via improved proteostasis. Despite improved physiological fitness, bmm overexpression did not extend lifespan. Taken together, these data show that bmm overexpression has broad beneficial effects on physiological fitness, but these effects did not impact lifespan.

Original languageEnglish (US)
Pages (from-to)6481-6506
Number of pages26
JournalAging
Volume14
Issue number16
DOIs
StatePublished - 2022

Bibliographical note

Funding Information:
This study was supported by NIH grant R01AG055452 to Dr. Douglas G. Mashek. The metabolomic and lipidomic studies were supported by UW Nathan Shock Center of Excellence on the Biology of Aging grant P30AG013280 and the Northwest Metabolomics Research Center and NIH grant S10 OD021562 to Dr. Daniel Raftery. Dr. Daniel E. L. Promislow was supported by NIH grant R01AG049494. Dr. Timothy D. Heden was supported by K01 grant DK125258. Dr. Charles P. Najt was supported by NIH grant K99AG070104 and AHA grant 20POST35180115.

Publisher Copyright:
© 2022 Shang et al.

Keywords

  • Brummer
  • Lipolysis
  • Physiological fitness
  • Proteostasis
  • Stress resistance

PubMed: MeSH publication types

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

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