Caenorhabditis elegans DBL-1/BMP regulates lipid accumulation via interaction with insulin signaling

James F. Clark, Michael Meade, Gehan Ranepura, David H. Hall, Cathy Savage-Dunn

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Metabolic homeostasis is coordinately controlled by diverse inputs. Understanding these regulatory networks is vital to combating metabolic disorders. The nematode Caenorhabditis elegans has emerged as a powerful, genetically tractable model system for the discovery of lipid regulatory mechanisms. Here we introduce DBL-1, the C. elegans homolog of bone morphogenetic protein 2/4 (BMP2/4), as a significant regulator of lipid homeostasis. We used neutral lipid staining and a lipid droplet marker to demonstrate that both increases and decreases in DBL-1/BMP signaling result in reduced lipid stores and lipid droplet count. We find that lipid droplet size, however, correlates positively with the level of DBL-1/ BMP signaling. Regulation of lipid accumulation in the intestine occurs through non-cell-autonomous signaling, since expression of SMA-3, a Smad signal transducer, in the epidermis (hypodermis) is sufficient to rescue the loss of lipid accumulation. Finally, genetic evidence indicates that DBL-1/BMP functions upstream of Insulin/IGF-1 Signaling in lipid metabolism. We conclude that BMP signaling regulates lipid metabolism in C. elegans through interorgan signaling to the Insulin pathway, shedding light on a less well-studied regulatory mechanism for metabolic homeostasis.

Original languageEnglish (US)
Pages (from-to)343-351
Number of pages9
JournalG3: Genes, Genomes, Genetics
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2018

Keywords

  • BMP
  • Caenorhabditis elegans
  • Homeostasis
  • Insulin
  • Lipid

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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