The New Therapeutic Approaches in the Treatment of Non-Alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease which is characterized by extremely complex pathogenetic mechanisms and multifactorial etiology. Some of the many pathophysiological mechanisms involved in the development of NAFLD include oxidative stress, impaired mitochondrial metabolism, inflammation, gut microbiota, and interaction between the brain-liver-axis and the regulation of hepatic lipid metabolism. The new therapeutic approaches in the treatment of NAFLD are targeting some of these milestones along the pathophysiological pathway and include drugs like agonists of peroxisome proliferator-activated receptors (PPARs), glucagon-like peptide-1 (GLP-1) agonists, sodium/glucose transport protein 2 (SGLT2) inhibitors, farnesoid X receptor (FXR) agonists, probiotics, and symbiotics. Further efforts in biomedical sciences should focus on the investigation of the relationship between the microbiome, liver metabolism, and response to inflammation, systemic consequences of metabolic syndrome.

Keywords: dysbiosis; lipotoxicity; new therapeutic modalities; non-alcoholic fatty liver disease; organelle dysfunction.

Figure 1

Molecular mechanisms in the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Abbreviations: NAFLD, non-alcoholic fatty liver disease; FFAs, free fatty acids; TNF-α, tumor necrosis factor alpha; IL-6, interleukin 6; IL12, interleukin 12; TG, triglycerides; ROS, reactive oxygen species; LPS, lipopolysaccharide; PAMPs, pathogen-associated molecular patterns; DAMPs, damage-associated molecular patterns; TLR4, toll-like receptors; NLP3, NOD-, LRR-, and pyrin domain-containing protein 3.

Figure 2

Therapeutic algorithm for NAFLD treatment.