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Updated: Aug 11, 2026
Inducing and Characterizing Vesicular Steatosis in Differentiated HepaRG Cells
Published on: July 18, 2019
Curculigoside A alleviates metabolic dysfunction-associated steatohepatitis by targeting Rab30 to improve lipid
Yue Shi1, Yiwen Han2, Hairong Zhang3
1School of Pharmacy, Nantong University, Nantong, Jiangsu 226019, China; Department of Pharmacy, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital, Yancheng, Jiangsu 224001, China.
Background:
Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by hepatocellular lipid overload, hepatic inflammation, and fibrotic remodeling. Impaired lipid droplet clearance and fatty acid oxidation (FAO) contribute to MASH progression, yet the molecular regulators coordinating these processes remain insufficiently defined.
Purpose:
This study aimed to investigate whether and how Rab30 regulates hepatic lipid homeostasis and to develop a Rab30-related pharmacological intervention strategy for MASH.
Methods:
A diet-induced MASH model was established in mice. Hepatocyte-specific Rab30 overexpression or knockdown was achieved using viral vectors. Potential curculigoside A (CA)-Rab30 engagement was assessed using complementary computational prediction and target-engagement approaches. CA was evaluated in vitro and in vivo for pharmacological efficacy. Palmitic acid-treated hepatocytes were used to examine cell viability, oxidative stress, lipid metabolism, autophagy, and senescence.
Results:
Rab30 protein abundance declined progressively in hepatocytes during diet-induced MASH development. Hepatocyte-specific Rab30 overexpression attenuated liver injury, steatosis, inflammation, and fibrogenesis in diet-induced MASH mice. In stressed hepatocytes, Rab30 overexpression reduced oxidative stress and senescence-associated changes. Mechanistically, Rab30 promoted autophagy-dependent lipid droplet clearance and FAO. CA showed potential engagement with Rab30, preserved Rab30 protein abundance under metabolic stress, and protected hepatocytes from lipometabolic dysfunction, oxidative stress, and senescence. In vivo, CA ameliorated diet-induced MASH pathology, and this effect was substantially weakened by hepatocellular Rab30 knockdown.
Conclusion:
This study identifies Rab30 as an important regulator of hepatic lipid homeostasis by coordinating autophagy-dependent lipid droplet clearance and FAO, and supports CA as a pharmacological Rab30 protein stabilizer with potential for MASH intervention.
