Hepatic Peroxisomal Dysfunction in Alcohol-Associated Liver Disease

Peroxisomes are abundant metabolic organelles in hepatocytes and play essential roles in lipid metabolism, reactive oxygen species homeostasis, bile acid synthesis, and cellular adaptation to metabolic stress. Alcohol disrupts hepatic peroxisomal function, but the contribution of this organelle dysfunction to alcohol-associated liver disease (ALD) remains incompletely understood.

Our laboratory investigates how impaired hepatic peroxisomal function alters liver metabolism and influences the development and progression of ALD. We are particularly interested in the roles of peroxisomes in bile acid and lipid metabolism, alcohol metabolism, cellular stress responses and the response to chronic liver injury and fibrosis. We also examine how metabolic consequences of hepatic peroxisomal dysfunction extend beyond the liver and affect other organs.

Intestinal Homeostasis in Alcohol-Associated Liver Disease

The intestinal epithelium forms a critical barrier between the host and the gut environment and plays an active role in nutrient handling, innate immunity and communication with the microbiome. Chronic alcohol exposure disrupts these functions, leading to impaired epithelial integrity, altered antimicrobial defenses and increased movement of microbial products from the intestine to the liver.

Our laboratory investigates the cellular and molecular mechanisms that maintain intestinal homeostasis and how these mechanisms are disrupted by alcohol. Areas of interest include epithelial barrier function, nutrient and micronutrient homeostasis, cellular stress responses and interactions between the intestinal epithelium and gut microbiome. Our goal is to understand how changes originating in the intestine contribute to liver injury and to identify approaches that restore intestinal homeostasis and reduce disease progression.

Bidirectional Gut-Liver Communication in Disease and Recovery

The gut-liver axis is traditionally viewed primarily as a pathway through which intestinal dysfunction contributes to liver disease. However, communication between these organs is bidirectional: changes in hepatic metabolism and function can also influence the intestinal environment. Understanding this reciprocal communication is a major focus of our research.

We investigate how liver-derived metabolites and signaling molecules influence intestinal epithelial function, innate immunity and the gut microbiome, as well as how intestinal-derived factors subsequently affect hepatic metabolism, inflammation and injury. We are particularly interested in how disruption of these communication networks can establish self-reinforcing cycles that promote disease progression.

References

• Hogerty Carolina, Zhao Yantao, Wang Weiran, Weinman Steven A., Zhong Wei. 2026. Peroxisomes in liver diseases: From metabolite quality control to inter-organelle and inter-organ signaling. Biomolecules, 16(6), 895. https://pubmed.ncbi.nlm.nih.gov/42352361/
• Yue Ruichao, Wei Xiaoyuan, Hao Liuyi, Dong Haibo, Guo Wei, Sun Xinguo, Zhao Jiangchao, Zhou Zhanxiang, Zhong Wei. 2023. IL-22 ameliorates alcohol-induced liver injury in mice through regulating intestinal antimicrobial defense, microbiome symbiosis and gut barrier function. Frontiers in Immunology, 14, 1289356. https://pubmed.ncbi.nlm.nih.gov/37908362/
• Yue Ruichao, Chen Guan-yuan, Xie Guoxiang, Hao Liuyi, Guo Wei, Sun Xinguo, Jia Wei, Zhang Qibin, Zhou Zhanxiang, Zhong Wei. 2021. Activation of PPARα - catalase pathway reverses alcoholic liver injury via upregulating NAD synthesis and accelerating alcohol clearance. Free Radical Biology and Medicine. https://pubmed.ncbi.nlm.nih.gov/34390780/
• Zhong Wei, Wei Xiaoyuan, Hao Liuyi, Lin Tai-Du, Yue Ruichao, Sun Xinguo, Guo Wei, Dong Haibo, Li Tianjiao, Ali AhmadiR, Sun Zhaoli, Zhang Qibin, Zhao Jiangchao, Zhou Zhanxiang. 2020. Paneth cell dysfunction mediates alcoholic steatohepatitis through promoting bacterial translocation in mice: role of zinc deficiency. Hepatology. https://pubmed.ncbi.nlm.nih.gov/31520476/