RRC ID 51522
Author Clark JF, Meade M, Ranepura G, Hall DH, Savage-Dunn C.
Title Caenorhabditis elegans DBL-1/BMP Regulates Lipid Accumulation via Interaction with Insulin Signaling.
Journal G3 (Bethesda)
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.
Volume 8(1)
Pages 343-351
Published 2018-1-4
DOI 10.1534/g3.117.300416
PII g3.117.300416
PMID 29162682
PMC PMC5765361
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Gene Expression Regulation, Developmental Gene Regulatory Networks Homeostasis Insulin / genetics Insulin / metabolism* Insulin-Like Growth Factor I / genetics* Insulin-Like Growth Factor I / metabolism Lipid Droplets / metabolism Lipid Metabolism / genetics* Neuropeptides / genetics* Neuropeptides / metabolism Organ Specificity Signal Transduction Transforming Growth Factor beta / genetics* Transforming Growth Factor beta / metabolism
IF 2.781
Times Cited 7
C.elegans tm331