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

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.

journal_name

Aging Cell

journal_title

Aging cell

authors

Dixit A,Sandhu A,Modi S,Shashikanth M,Koushika SP,Watts JL,Singh V

doi

10.1111/acel.13160

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

e13160

issue

6

eissn

1474-9718

issn

1474-9726

journal_volume

19

pub_type

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