Interorganelle competition for linoleic acid underlies steatotic liver pathology.

ABSTRACT: Lipid droplets (LDs) are traditionally viewed as protective organelles that sequester potentially cytotoxic lipids. However, whether and how LD biogenesis in pathological contexts actively rewires interorganelle lipid homeostasis to drive organelle dysfunction and disease progression remains unexplored. Here, we identify the adipocyte-enriched protein calsyntenin 3β (CLSTN3B) as a critical promoter of metabolic dysfunction-associated steatotic liver disease (MASLD). CLSTN3B, an ER-LD contact protein previously shown to support LD maturation in adipocytes, is robustly induced in mouse hepatocytes by peroxisome proliferator-activated receptor γ (PPARγ) in response to dietary caloric overload. CLSTN3B drives LD biogenesis and neutral lipid storage by stabilizing hemifusion-like ER-LD membrane

SUBMITTER: Zhang C 

PROVIDER: S-EPMC12803078 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature