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

Cell Syst. 2017 Jul 26;5(1):38-52.e4. doi: 10.1016/j.cels.2017.06.004. Epub 2017 Jul 19.

Abstract

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.

Keywords: C. elegans; HLH-30; RNA-seq; lipid droplets; proteomics; starvation; transcriptomics; vitellogenins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics*
  • Gene Knockout Techniques
  • Lipid Droplets
  • Lipoproteins / metabolism*
  • Particle Size
  • Proteomics
  • RNA Interference
  • Sequence Analysis, RNA
  • Starvation / metabolism*
  • Vitellogenins / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Caenorhabditis elegans Proteins
  • HLH-30 protein, C elegans
  • Lipoproteins
  • Vitellogenins