Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

An Update on Chemokine System in the Development of NAFLD

Version 1 : Received: 18 May 2022 / Approved: 19 May 2022 / Online: 19 May 2022 (07:51:15 CEST)

A peer-reviewed article of this Preprint also exists.

Nagata, N.; Chen, G.; Xu, L.; Ando, H. An Update on the Chemokine System in the Development of NAFLD. Medicina 2022, 58, 761. Nagata, N.; Chen, G.; Xu, L.; Ando, H. An Update on the Chemokine System in the Development of NAFLD. Medicina 2022, 58, 761.


Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Sustained hepatic inflammation is a key driver of the transition from simple fatty liver to nonalcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. Hepatic inflammation is orchestrated by chemokines, a family of chemoattractant cytokines, which are produced by hepatocytes, Kupffer cells (liver resident macrophages), hepatic stellate cells, endothelial cells, and vascular smooth muscle cells. Over the last three decades, accumulating evidence from both clinical and experimental investigations demonstrated that chemokines and their receptors are increased in the livers of NAFLD patients and that CC chemokine ligand (CCL) 2 and CCL5, in particular, play a pivotal role in inducing insulin resistance, steatosis, inflammation, and fibrosis in the liver disease. Cenicriviroc (CVC), a dual antagonist of these chemokine’s receptor, CCR2 and CCR5, has been tested in clinical trials in patients with NASH-associated liver fibrosis. Additionally, recent studies revealed that other chemokines, such as CCL3, CCL25, CX3C chemokine ligand 1 (CX3CL1), CXC chemokine ligand 1 (CXCL1), and CXCL16 can also contribute to the pathogenesis of NAFLD. Here, we review recent updates on the roles of chemokines in the development of NAFLD and their blockade as potential therapeutic approaches.


chemokine; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; inflammation; immune cells


Medicine and Pharmacology, Gastroenterology and Hepatology

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