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Muscle-Specific Lipid Hydrolysis Prolongs Lifespan through Global Lipidomic Remodeling
oleh: Sebastian Schmeisser, Shaolin Li, Bertrand Bouchard, Matthieu Ruiz, Christine Des Rosiers, Richard Roy
Format: | Article |
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Diterbitkan: | Elsevier 2019-12-01 |
Deskripsi
Summary: 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. : Schmeisser et al. describe a longevity pathway that originates in muscle tissue through PKA-mediated ATGL-dependent depletion of intramyocellular lipid droplets. This, together with the PLA2 ortholog IPLA-7, affects inter-tissular signaling through the formation of “lipokines,” modulating metabolic homeostasis and extending the lifespan via neuronal AMPK and NHR-80. Keywords: lipid metabolism, muscle lipids, lifespan, lipokines, myokines, PKA, ATGL, AMPK, NHR-80, phospholipase A2