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

Author:

Arruda Vinícius Marques12,Azevedo Gabriela Tolentino12,Granato Maria Júlia Maia Gonçalves1,Matos André Carlos Pereira2ORCID,Araújo Thaise Gonçalves2ORCID,Guerra Joyce Ferreira da Costa1ORCID

Affiliation:

1. Laboratory of Metabolic Biochemistry and Redox Processes, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas 38700-002, Brazil

2. Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas 38700-002, Brazil

Abstract

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.

Funder

Fundação de Amparo à Pesquisa do Estado de Minas Gerais

Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Conselho Nacional de Desenvolvimento Científico e Tecnológico

National Institute of Science and Technology in Theranostics and Nanobiotechnology

Publisher

MDPI AG

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