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Research Paper|Volume 14, Issue 16|pp 6481—6506

Systemic lipolysis promotes physiological fitness in Drosophila melanogaster

Linshan Shang1, Elizabeth Aughey2, Huiseon Kim1, Timothy D. Heden1, Lu Wang3, Charles P. Najt1, Nicholas Esch1, Sophia Brunko1, Juan E. Abrahante4, Marissa Macchietto5, Mara T. Mashek1, Todd Fairbanks2, Daniel E. L. Promislow6,7, Thomas P. Neufeld2, Douglas G. Mashek1,8
  • 1Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA
  • 2Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA
  • 3Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA
  • 4University of Minnesota Informatics Institute, Minneapolis, MN 55455, USA
  • 5Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, USA
  • 6Department of Biology, University of Washington, Seattle, WA 98195, USA
  • 7Department of Lab Medicine and Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA
  • 8Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, MN 55455, USA
Received: March 4, 2022Accepted: August 15, 2022Published: August 30, 2022
https://doi.org/10.18632/aging.204251

Copyright: © 2022 Shang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.