Oxidative Stress and Annexin A2 Differential Expression in Free Fatty Acids-Induced Non-Alcoholic Fatty Liver Disease in HepG2 Cells

• Published in: International journal of molecular sciences 2024-09, Vol.25 (17), p.9591
• Main Authors: Arruda, Vinícius Marques, Azevedo, Gabriela Tolentino, Granato, Maria Júlia Maia Gonçalves, Matos, André Carlos Pereira, Araújo, Thaise Gonçalves, Guerra, Joyce Ferreira da Costa
• Format: Article
• Language: English
• Subjects: Annexin A2 - genetics; Annexin A2 - metabolism; Cytokines; Cytotoxicity; Fatty acids; Fatty Acids, Nonesterified - metabolism; Hep G2 Cells; hepatic steatosis; HepG2 cells; Humans; Inflammation; Keratin 17; Lipid Metabolism - drug effects; Lipid peroxidation; Lipid Peroxidation - drug effects; Lipids; lipotoxicity; Liver diseases; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - pathology; Oxidative stress; Oxidative Stress - drug effects; Pathogenesis; Proteins
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25179591

Non-alcoholic fatty liver disease (NAFLD) is a rising global burden, affecting one in four adults. Despite the increasing prevalence of NAFLD, the exact cellular and molecular mechanisms remain unclear, and effective therapeutic strategies are still limited. In vitro models of NAFLD are critical to understanding the pathogenesis and searching for effective therapies; thus, we evaluated the effects of free fatty acids (FFAs) on NAFLD hallmarks and their association with the modulation of Annexin A2 (ANXA2) and Keratin 17 (KRT17) in HepG2 cells. Our results show that oleic and palmitic acids can differentially induce intracellular lipid accumulation, cell death, and promote oxidative stress by increasing lipid peroxidation, protein carbonylation, and antioxidant defense depletion. Moreover, a markedly increased expression of inflammatory cytokines demonstrated the activation of inflammation pathways associated with lipotoxicity and oxidative stress. ANXA2 overexpression and KRT17 nuclear translocation were also observed, supporting the role of both molecules in the progression of liver disease. Taken together, these data provide insights into the interplay between ANXA2 and KRT17 in NAFLD, paving the way for understanding molecular mechanisms involved with the disease and developing new therapeutic strategies.