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Augmentation of Glucotoxicity, Oxidative Stress, Apoptosis and Mitochondrial Dysfunction in HepG2 Cells by Palmitic Acid
Open accessAbstract
Hyperglycemia and hyperlipidemia are the hallmarks of diabetes and obesity. Experimental and epidemiological studies have suggested that dietary management and caloric restriction are beneficial in reducing the complications of diabesity. Studies have suggested that increased availability of energy metabolites like glucose and saturated fatty acids induces metabolic, oxidative, and mitochondrial stress, accompanied by inflammation that may lead to chronic complications in diabetes. In the present study, we used human hepatoma HepG2 cells to investigate the effects of high glucose (25 mM) and high palmitic acid (up to 0.3 mM) on metabolic-, inflammatory-, and redox-stress-associated alterations in these cells. Our results showed increased lipid, protein, and DNA damage, leading to caspase-dependent apoptosis and mitochondrial dysfunction. Glucolipotoxicity increased ROS production and redox stress appeared to alter mitochondrial membrane potential and bioenergetics. Our results also demonstrate the enhanced ability of cytochrome P450s-dependent drug metabolism and antioxidant adaptation in HepG2 cells treated with palmitic acid, which was further augmented with high glucose. Altered NF-kB/AMPK/mTOR-dependent cell signaling and inflammatory (IL6/TNF-α) responses were also observed. Our results suggest that the presence of high-energy metabolites enhances apoptosis while suppressing autophagy by inducing inflammatory and oxidative stress responses that may be responsible for alterations in cell signaling and metabolism.
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“ROS accumulation triggers damaging cascades: a decrease in mitochondrial membrane potential, activation of caspases 3/7, apoptosis, and ER stress and inflammation via NF-κB [90,152,153,154,155].”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [90]
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Metadata
- Authors
- Alnahdi, A., John, A., & Raza, H.
- Affiliations
- United Arab Emirates University (AE)
- Corresponding author
- Raza, Haider
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2019-08-22
- Volume
- 11
- Issue
- 9
- Pages
- 1979
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC6770774
- OpenAlex
- W2969456983
- Cited by
- 134
- References
- 60
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 26 · 2023: 16 · 2022: 26 · 2021: 22 · 2020: 6 · 2019: 1
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences (MRG-18/2013-2014)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- palmitic acid, glucolipotoxicity, high glucose, oxidative stress, apoptosis, mitochondrial dysfunction, HepG2 cells, hepatocytes, redox stress, mitochondrial membrane potential, antioxidant adaptation, autophagy, diabesity, saturated fatty acids
- MeSH terms
- Autophagy, Energy Metabolism, Glucose, Humans, Mitochondria, Liver, Signal Transduction, NF-kappa B, Apoptosis, Oxidative Stress, Inflammation Mediators, Palmitic Acid, Hepatocytes, AMP-Activated Protein Kinases, Hep G2 Cells, TOR Serine-Threonine Kinases
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