Muscle-Specific Lipid Hydrolysis Prolongs Lifespan through Global Lipidomic Remodeling

Cell Rep. 2019 Dec 24;29(13):4540-4552.e8. doi: 10.1016/j.celrep.2019.11.090.

Abstract

A growing body of evidence suggests that changes in fat metabolism may have a significant effect on lifespan. Accumulation of lipid deposits in non-adipose tissue appears to be critical for age-related pathologies and may also contribute to the aging process itself. We established a model of lipid storage in muscle cells of C. elegans to reveal a mechanism that promotes longevity non-cell-autonomously. Here, we describe how muscle-specific activation of adipose triglyceride lipase (ATGL) and the phospholipase A2 (PLA2) ortholog IPLA-7 collectively affect inter-tissular communication and systemic adaptation that requires the activity of AMP-dependent protein kinase (AMPK) and a highly conserved nuclear receptor outside of the muscle. Our data suggest that muscle-specific bioactive lipid signals, or "lipokines," are generated following triglyceride breakdown and that these signals impinge on a complex network of genes that modify the global lipidome, consequently extending the lifespan.

Keywords: AMPK; ATGL; NHR-80; PKA; lifespan; lipid metabolism; lipokines; muscle lipids; myokines; phospholipase A2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylate Kinase / metabolism
  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Diet
  • Enzyme Activation
  • Hydrolysis
  • Lipid Droplets / metabolism
  • Lipidomics*
  • Lipids / chemistry*
  • Lipolysis
  • Longevity / physiology*
  • Muscle Cells / metabolism
  • Muscles / metabolism*
  • Organ Specificity
  • Transcription Factors / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Lipids
  • Transcription Factors
  • Cyclic AMP-Dependent Protein Kinases
  • Adenylate Kinase