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.

Influence of Dietary Berberine on Liver Immune Response and Intestinal Health of Black Sea Bream (Acanthopagrus schlegelii) Fed with Normal and High-Lipid Diets

“…Similarly, other hepatic lipid-lowering additives also showed an anti-inflammation effect in black sea bream, such as L-carnitine and bile acid [29], choline [30] and fenofibrate [31]. Studies in mice found that berberine alleviated nonalcoholic steatohepatitis by inhibiting phosphoinositide 3-kinase (PI3K), NF-κB, and IL-8 in the cysteine X cysteine ligand 12/cysteine X cysteine receptor 4 (CXCL12/CXCR4) inflammatory signaling pathway [33], or by activating AMPK signaling and decreasing the TLR4/ NF-κB-p65 signaling pathway [34]. In addition, the antiinflammatory effect of berberine has been reported in 3T3-L1 adipocytes [35] and visceral adipose tissue [36].…”

Synergistic Effect of Dietary Inactivated Lactobacillus plantarum and Berberine Supplementation on Growth Performance, Antioxidant Capacity, and Immune Function of Juvenile Black Sea Bream (Acanthopagrus schlegelii)

“…The immunestimulating ability of berberine is attributable to its influence on enteric glial cells (EGC), bone marrow-derived dendritic glial cells (BMDCs), T cells, and gut epithelial cells (IEC) [76]. Another mechanism by which berberine modulates immune response could be by attenuating the TLR4/NF-κB-p65 signaling pathway and activating the adenosine monophosphate-(AMP-) activated protein kinase (AMPK) signaling [77].…”

YNCRG Alleviated Hepatic Steatosis in Metabolic Syndrome Model Rats by Improving Lipid Metabolism and Chronic Inflammatory Reaction

“…The signals generated by TLRs are transduced through the NF-κB pathway to recruit pro-inflammatory cytokines [29], hence, the activation of the NF-κB pathway can promote the production of TNF-α, IL-1β, IL-6, and other pro-inflammatory factors, which are closely related to the development of NAFLD. Inhibiting the NF-κB signaling pathway and related inflammatory factors can significantly improve the symptoms of NAFLD in rats [30,31]. Furthermore, the progression of NAFLD to NASH requires the recruitment of activated macrophages, and CCL2 and ICAM-1 promote the activity of macrophages [32].…”