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bioRxiv · 10.1101/2025.08.26.672501

MBOAT7 and CDS2 coordinate lipid droplet dynamics and cholesterol metabolism in liver

Xu, J.·Zhang, J.·Wang, W.·Su, H.·Chen, S.·Ding, M.·Huang, X.
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Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent disorder worldwide characterized by the accumulation of hepatic lipid droplets (LDs). However, the mechanisms by which hepatocytes adapt to the dynamic changes in LD morphology to maintain metabolic homeostasis remains incompletely understood. Here, we show that MBOAT7, a known MASLD-associated protein, cooperates with CDS2 to regulate lipid droplet dynamics and lipid metabolism. Under physiological conditions, their interaction in the endoplasmic reticulum (ER) maintains metabolic homeostasis. Disruption of this interaction, such as through CDS2 knockdown or loss of function, triggers an adaptive response wherein MBOAT7 translocates to ER-LD contact sites in a RAB1-dependent manner. This redistribution inhibits DGAT2-mediated LD growth and promotes lipolysis. Our findings highlight the redistribution of MBOAT7 to ER-LD contacts serves as a critical mechanism for adaptive control LD size and lipid metabolic homeostasis.

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Xu, J., Zhang, J., Wang, W., Su, H., Chen, S., Ding, M., Huang, X.. 2025-08-29. MBOAT7 and CDS2 coordinate lipid droplet dynamics and cholesterol metabolism in liver. https://doi.org/10.1101/2025.08.26.672501

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