C. elegansDBL-1/BMP Regulates Lipid Accumulation via Interaction with Insulin Signaling

Metabolic homeostasis is coordinately controlled by diverse inputs, which must be understood to combat metabolic disorders. Here we introduce DBL-1, theC. elegansBMP2/4 homolog, 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 (IIS) in lipid metabolism. We conclude that BMP signaling regulates lipid metabolism inC. elegansthrough inter-organ signaling to IIS, shedding light on a less well-studied regulatory mechanism for metabolic homeostasis.