Inhibition of CCL19 benefits non‑alcoholic fatty liver disease by inhibiting TLR4/NF‑κB‑p65 signaling.

Abstract

Non‑alcoholic fatty liver disease (NAFLD), which affects approximately one‑third of the general population, has become a global health problem. Thus, more effective treatments for NAFLD are urgently required. In the present study, high levels of C‑C motif ligand 19 (CCL19), signaling pathways such as Toll‑like receptor 4 (TLR4)/nuclear factor‑κB (NF‑κB), and proinflammatory factors including interleukin‑6 (IL‑6) and tumor necrosis factor‑α (TNF‑α) were detected in NAFLD patients, thereby indicating that there may be an association between CCL19 and these factors in NAFLD progression. Using a high‑fat diet (HFD), the present study generated a Sprague‑Dawley rat model of NAFLD, which displayed dyslipidemia with increased levels of plasma aspartate aminotransferase, alanine aminotransferase, total cholesterol and triglyceride. Dyslipidemia, liver histopathology and gene expression analyses indicated that the NAFLD model was successfully induced by HFD, and metformin and berberine (BBR) were effective treatments for NAFLD. HFD‑induced CCL19 levels and associated factors were markedly reduced by the two drug treatments. In addition, metformin or BBR alone significantly promoted adenosine monophosphate‑activated protein kinase (AMPK) phosphorylation, which was inhibited by HFD. These results demonstrated that metformin and BBR could improve NAFLD, which may be via the activation of AMPK signaling, and the high expression of CCL19 in NAFLD was significantly reduced by metformin and BBR. It could be inferred that inhibition of CCL19 may be an effective treatment for NAFLD.