Cited by 134Mitochondrial Function and PathologyMetabolism, Diabetes, and CancerDiet, Metabolism, and Disease

Augmentation of Glucotoxicity, Oxidative Stress, Apoptosis and Mitochondrial Dysfunction in HepG2 Cells by Palmitic Acid

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Alnahdi, Arwa, John, Annie, Raza, Haider·2019·Nutrients

Abstract

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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Crossref · 10.3390/nu11091979

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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.

    “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]

    The Discussion (page unavailable) links increased ROS in high-glucose/palmitic-acid-treated HepG2 cells to loss of mitochondrial membrane potential, mitochondrial dysfunction, and apoptosis. The Results report caspase-3 cleavage and NF-κB translocation associated with inflammatory signaling. The paper does not establish caspase-7 activation or an ROS-to-ER-stress pathway via NF-κB; ER stress is mentioned only as background in the Introduction. (LLM, conf=0.87)

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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)
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
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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