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 journalArticle

3 Citations (Scopus)

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

Fingerprint

Caenorhabditis elegans
Insulin
Lipids
Homeostasis
Lipid Metabolism
Bone Morphogenetic Protein 4
Bone Morphogenetic Protein 2
Subcutaneous Tissue
Transducers
Insulin-Like Growth Factor I
Epidermis
Intestines
Staining and Labeling
Lipid Droplets

Keywords

  • BMP
  • Caenorhabditis elegans
  • Homeostasis
  • Insulin
  • Lipid

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Caenorhabditis elegans DBL-1/BMP regulates lipid accumulation via interaction with insulin signaling. / Clark, James F.; Meade, Michael; Ranepura, Gehan; Hall, David H.; Savage-Dunn, Cathy.

In: G3: Genes, Genomes, Genetics, Vol. 8, No. 1, 01.01.2018, p. 343-351.

Research output: Contribution to journalArticle

Clark, James F. ; Meade, Michael ; Ranepura, Gehan ; Hall, David H. ; Savage-Dunn, Cathy. / Caenorhabditis elegans DBL-1/BMP regulates lipid accumulation via interaction with insulin signaling. In: G3: Genes, Genomes, Genetics. 2018 ; Vol. 8, No. 1. pp. 343-351.
@article{5bad282057764fb6bc8f5d56e609e7fe,
title = "Caenorhabditis elegans DBL-1/BMP regulates lipid accumulation via interaction with insulin signaling",
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.",
keywords = "BMP, Caenorhabditis elegans, Homeostasis, Insulin, Lipid",
author = "Clark, {James F.} and Michael Meade and Gehan Ranepura and Hall, {David H.} and Cathy Savage-Dunn",
year = "2018",
month = "1",
day = "1",
doi = "10.1534/g3.117.300416",
language = "English (US)",
volume = "8",
pages = "343--351",
journal = "G3 (Bethesda, Md.)",
issn = "2160-1836",
publisher = "Genetics Society of America",
number = "1",

}

TY - JOUR

T1 - Caenorhabditis elegans DBL-1/BMP regulates lipid accumulation via interaction with insulin signaling

AU - Clark, James F.

AU - Meade, Michael

AU - Ranepura, Gehan

AU - Hall, David H.

AU - Savage-Dunn, Cathy

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - BMP

KW - Caenorhabditis elegans

KW - Homeostasis

KW - Insulin

KW - Lipid

UR - http://www.scopus.com/inward/record.url?scp=85039931896&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85039931896&partnerID=8YFLogxK

U2 - 10.1534/g3.117.300416

DO - 10.1534/g3.117.300416

M3 - Article

C2 - 29162682

AN - SCOPUS:85039931896

VL - 8

SP - 343

EP - 351

JO - G3 (Bethesda, Md.)

JF - G3 (Bethesda, Md.)

SN - 2160-1836

IS - 1

ER -