Regulation of C. elegans fat uptake and storage by acyl-CoA synthase-3 is dependent on NR5A family nuclear hormone receptor nhr-25

Brendan C Mullaney, Raymond D Blind, George A Lemieux, Carissa L Perez, Ida C Elle, Nils J. Færgeman, Marc R Van Gilst, Holly A Ingraham, Kaveh Ashrafi

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

Acyl-CoA synthases are important for lipid synthesis and breakdown, generation of signaling molecules, and lipid modification of proteins, highlighting the challenge of understanding metabolic pathways within intact organisms. From a C. elegans mutagenesis screen, we found that loss of ACS-3, a long-chain acyl-CoA synthase, causes enhanced intestinal lipid uptake, de novo fat synthesis, and accumulation of enlarged, neutral lipid-rich intestinal depots. Here, we show that ACS-3 functions in seam cells, epidermal cells anatomically distinct from sites of fat uptake and storage, and that acs-3 mutant phenotypes require the nuclear hormone receptor NHR-25, a key regulator of C. elegans molting. Our findings suggest that ACS-3-derived long-chain fatty acyl-CoAs, perhaps incorporated into complex ligands such as phosphoinositides, modulate NHR-25 function, which in turn regulates an endocrine program of lipid uptake and synthesis. These results reveal a link between acyl-CoA synthase function and an NR5A family nuclear receptor in C. elegans.
OriginalsprogEngelsk
TidsskriftCell Metabolism
Vol/bind12
Udgave nummer4
Sider (fra-til)398-410
Antal sider13
ISSN1550-4131
DOI
StatusUdgivet - 6. okt. 2010

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