Neuronal control of lipid metabolism by STR-2 G protein-coupled receptor promotes longevity in Caenorhabditis elegans

Anubhuti Dixit, Anjali Sandhu, Souvik Modi, Meghana Shashikanth, Sandhya P. Koushika, Jennifer L. Watts, Varsha Singh

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)
35 Downloads (Pure)

Abstract

The G protein-coupled receptor (GPCR) encoding family of genes constitutes more than 6% of genes in Caenorhabditis elegans genome. GPCRs control behavior, innate immunity, chemotaxis, and food search behavior. Here, we show that C. elegans longevity is regulated by a chemosensory GPCR STR-2, expressed in AWC and ASI amphid sensory neurons. STR-2 function is required at temperatures of 20°C and higher on standard Escherichia coli OP50 diet. Under these conditions, this neuronal receptor also controls health span parameters and lipid droplet (LD) homeostasis in the intestine. We show that STR-2 regulates expression of delta-9 desaturases, fat-5, fat-6 and fat-7, and of diacylglycerol acyltransferase dgat-2. Rescue of the STR-2 function in either AWC and ASI, or ASI sensory neurons alone, restores expression of fat-5, dgat-2 and restores LD stores and longevity. Rescue of stored fat levels of GPCR mutant animals to wild-type levels, with low concentration of glucose, rescues its lifespan phenotype. In all, we show that neuronal STR-2 GPCR facilitates control of neutral lipid levels and longevity in C. elegans.

Original languageEnglish
Article numbere13160
JournalAging Cell
Volume19
Issue number6
Early online date20 May 2020
DOIs
Publication statusPublished - 15 Jun 2020

Keywords

  • C. elegans
  • chemosensory GPCR
  • desaturases
  • diet
  • lipid metabolism
  • longevity
  • temperature

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

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