(+)Alpha-Lipoic Acid Regulates Lipid Metabolism Gene Expression and Lipidic Profile in a Cellular Model of Fatty Acid Overload

Lucia Longhitano; Daniele Tibullo; Tatiana Zuppelli; Simone Ronsisvalle; Enrico La Spina; Anna Nicolosi; Maria Antoci; Federica Maria Sipala; Fabio Galvano; Walter Currenti; Annalisa Santisi; Amer M. Alanazi; Guido Zanghì; Emanuela Tropea; Giovanni Li Volti; Ignazio Alberto Barbagallo

doi:10.31083/j.fbl2906209

Frontiers in Bioscience-Landmark (Jun 2024)

(+)Alpha-Lipoic Acid Regulates Lipid Metabolism Gene Expression and Lipidic Profile in a Cellular Model of Fatty Acid Overload

Lucia Longhitano,
Daniele Tibullo,
Tatiana Zuppelli,
Simone Ronsisvalle,
Enrico La Spina,
Anna Nicolosi,
Maria Antoci,
Federica Maria Sipala,
Fabio Galvano,
Walter Currenti,
Annalisa Santisi,
Amer M. Alanazi,
Guido Zanghì,
Emanuela Tropea,
Giovanni Li Volti,
Ignazio Alberto Barbagallo

Affiliations

Lucia Longhitano: Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Daniele Tibullo: Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Tatiana Zuppelli: Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Simone Ronsisvalle: Department of Drug Sciences, University of Catania, 95123 Catania, Italy
Enrico La Spina: Unità Operativa Complessa di Ematologia con Trapianto di Midollo Osseo, Azienda Ospedaliero-Universitaria Policlinico “G.Rodolico San Marco", 95123 Catania, Italy
Anna Nicolosi: Hospital Pharmacy Unit, Ospedale Cannizzaro, 95125 Catania, Italy
Maria Antoci: Laboratorio Arpa Sicilia, Viale Sicilia, 11, 97100 Ragusa (RG), Italy
Federica Maria Sipala: Department of Drug Sciences, University of Catania, 95123 Catania, Italy
Fabio Galvano: Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Walter Currenti: Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Annalisa Santisi: Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Amer M. Alanazi: Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia
Guido Zanghì: Department of General Surgery and Medical-Surgical Specialties, University of Catania, 95123 Catania, Italy
Emanuela Tropea: Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Giovanni Li Volti: Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Ignazio Alberto Barbagallo: Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy

DOI: https://doi.org/10.31083/j.fbl2906209
Journal volume & issue: Vol. 29, no. 6
p. 209

Abstract

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Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by hepatic fat accumulation, often progressing to severe liver injury, for which approved treatments are currently lacking. This study explores the potential therapeutic impact of alpha-lipoic acid (ALA), a natural compound crucial in lipid metabolism, on NAFLD using an in vitro model. Methods: HepG2 cells were treated with a palmitic acid:oleic acid (PA:OA) mixture, representing a cellular model of steatosis. Subsequent treatment with ALA at concentrations of 1 µM and 5 µM aimed to evaluate its effects on lipid content and metabolism. Real-time polymerase chain reaction (PCR), BODIPY staining, cytofluorimetric analysis, and lipidomics were used to assess gene expression, lipid droplet accumulation, and fatty acid profiles. Results: Our results showed that ALA significantly reduced lipid droplets in PA:OA-treated HepG2 cells, with a concentration-dependent effect. Analysis of fatty acid profiles demonstrated a decrease in palmitic acid levels with ALA treatment, while oleic acid reduction was observed only at the higher concentration. Moreover, ALA modulated the expression of genes involved in cholesterol biosynthesis and low-density lipoprotein (LDL) metabolism, indicating a potential role in lipid homeostasis. Further insights into molecular mechanisms revealed that ALA modulated peroxisome proliferator activated receptors (PPARs), specifically PPAR-alpha and PPAR-gamma, involved in fatty acid metabolism and insulin sensitivity. Finally, ALA counteracted the overexpression of thermogenic genes induced by exogenous fatty acids, suggesting a regulatory role in energy dissipation pathways. Conclusion: In conclusion, this study highlights ALA as a therapeutic agent in mitigating lipid accumulation and dysregulation in NAFLD.

Published in Frontiers in Bioscience-Landmark

ISSN: 2768-6701 (Print); 2768-6698 (Online)
Publisher: IMR Press
Country of publisher: Singapore
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry; Science: Biology (General)
Website: https://www.imrpress.com/journal/FBL

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