Being a vital cellular process, COPII vesicle trafficking has been found plays a crucial role in liver metabolism. However, its functions and the underlying mechanisms in systemic metabolic homeostasis have not been fully understood. Here, with a newly identified gene trap zebrafish line (sec31anju221), we show that compromised COPII vesicle trafficking leads to biphasic abnormal hepatic metabolism. During the larval stage, deficiency of COPII-mediated trafficking leads to activation of unfolded protein reaction (UPR) and the development of hepatic steatosis. By using epistasis analysis, we found eIF2a/ATF4 branch serves as the primary effector for liver steatosis. In adult sec31anju221 fish, the hepatosteatosis was reversed and the phenotype swing to glycogenic hepatopathy. Proteomic profiling and biochemical assay indicate sec31anju221 fish are in a state of hypothyroidism. Moreover, our study showed thyroid hormone treatment alleviates the metabolic defects. This study provides insights into processes of liver diseases associated with vesicle trafficking impairments and has expanded our understanding of the pathological interplay between thyroid and liver.
Compromised COPII vesicle trafficking leads to glycogenic hepatopathy in zebrafish
These authors contributed equally to the work
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Biologists @ 100 - join us in Liverpool in March 2025
We are excited to invite you to a unique scientific conference, celebrating the 100-year anniversary of The Company of Biologists, and bringing together our different communities. The conference will incorporate the Spring Meetings of the BSCB and the BSDB, the JEB Symposium Sensory Perception in a Changing World and a DMM programme on antimicrobial resistance. Find out more and register your interest to join us in March 2025 in Liverpool, UK.
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