Multi-omics Analyses of Starvation Responses Reveal a Central Role for Lipoprotein Metabolism in Acute Starvation Survival in C. elegans

TY - JOUR

T1 - Multi-omics Analyses of Starvation Responses Reveal a Central Role for Lipoprotein Metabolism in Acute Starvation Survival in C. elegans

AU - Harvald, Eva Bang

AU - Sprenger, Richard R.

AU - Dall, Kathrine Brændgaard

AU - Ejsing, Christer S.

AU - Nielsen, Ronni

AU - Mandrup, Susanne

AU - Brenes Murillo, Alejandro

AU - Larance, Mark

AU - Gartner, Anton

AU - Lamond, Angus

AU - Færgeman, Nils J.

N1 - This work was supported by The Danish Council for Independent Research, Natural Sciences (NJF: grant #310-95-23459).

PY - 2017/7/26

Y1 - 2017/7/26

N2 - Starvation causes comprehensive metabolic changes, which are still not fully understood. Here, we used quantitative proteomics and RNA sequencing to examine the temporal starvation responses in wild-type Caenorhabditis elegans and animals lacking the transcription factor HLH-30. Our findings show that starvation alters the abundance of hundreds of proteins and mRNAs in a temporal manner, many of which are involved in central metabolic pathways, including lipoprotein metabolism. We demonstrate that premature death of hlh-30 animals under starvation can be prevented by knockdown of either vit-1 or vit-5, encoding two different lipoproteins. We further show that the size and number of intestinal lipid droplets under starvation are altered in hlh-30 animals, which can be rescued by knockdown of vit-1. Taken together, this indicates that survival of hlh-30 animals under starvation is closely linked to regulation of intestinal lipid stores. We provide the most detailed poly-omic analysis of starvation responses to date, which serves as a resource for further mechanistic studies of starvation.

AB - Starvation causes comprehensive metabolic changes, which are still not fully understood. Here, we used quantitative proteomics and RNA sequencing to examine the temporal starvation responses in wild-type Caenorhabditis elegans and animals lacking the transcription factor HLH-30. Our findings show that starvation alters the abundance of hundreds of proteins and mRNAs in a temporal manner, many of which are involved in central metabolic pathways, including lipoprotein metabolism. We demonstrate that premature death of hlh-30 animals under starvation can be prevented by knockdown of either vit-1 or vit-5, encoding two different lipoproteins. We further show that the size and number of intestinal lipid droplets under starvation are altered in hlh-30 animals, which can be rescued by knockdown of vit-1. Taken together, this indicates that survival of hlh-30 animals under starvation is closely linked to regulation of intestinal lipid stores. We provide the most detailed poly-omic analysis of starvation responses to date, which serves as a resource for further mechanistic studies of starvation.

KW - C. elegans

KW - starvation

KW - HLH-30

KW - proteomics

KW - transcriptomics

KW - RNA-seq

KW - vitellogenins

KW - lipid droplets

U2 - 10.1016/j.cels.2017.06.004

DO - 10.1016/j.cels.2017.06.004

M3 - Article

C2 - 28734827

SN - 2405-4720

VL - 5

SP - 38-52.e4

JO - Cell Systems

JF - Cell Systems

IS - 1

ER -