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Cited by 125Lipid metabolism and biosynthesisLiver Disease Diagnosis and TreatmentMitochondrial Function and Pathology

Differential Effects of Oleic and Palmitic Acids on Lipid Droplet-Mitochondria Interaction in the Hepatic Cell Line HepG2

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Eynaudi, Andrea, Díaz-Castro, Francisco, Bórquez, Juan Carlos, Bravo-Sagua, Roberto, Parra, Valentina, Troncoso, Rodrigo·2021·Frontiers in Nutrition
DOI 10.3389/fnut.2021.775382PMC PMC8632770
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Abstract

Fatty acid overload, either of the saturated palmitic acid (PA) or the unsaturated oleic acid (OA), causes triglyceride accumulation into specialized organelles termed lipid droplets (LD). However, only PA overload leads to liver damage mediated by mitochondrial dysfunction. Whether these divergent outcomes stem from differential effects of PA and OA on LD and mitochondria joint dynamics remains to be uncovered. Here, we contrast how both fatty acids impact the morphology and interaction between both organelles and mitochondrial bioenergetics in HepG2 cells. Using confocal microscopy, we showed that short-term (2–24 h) OA overload promotes more and bigger LD accumulation than PA. Oxygen polarography indicated that both treatments stimulated mitochondrial respiration; however, OA favored an overall build-up of the mitochondrial potential, and PA evoked mitochondrial fragmentation, concomitant with an ATP-oriented metabolism. Even though PA-induced a lesser increase in LD-mitochondria proximity than OA, those LD associated with highly active mitochondria suggest that they interact mainly to fuel fatty acid oxidation and ATP synthesis (that is, metabolically “active” LD). On the contrary, OA overload seemingly stimulated LD-mitochondria interaction mainly for LD growth (thus metabolically “passive” LDs). In sum, these differences point out that OA readily accumulates in LD, likely reducing their toxicity, while PA preferably stimulates mitochondrial oxidative metabolism, which may contribute to liver damage progression.

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  • Oleic acid primarily promotes the formation of larger lipid droplets and facilitates the safe esterification of fatty acids into triglycerides, whereas palmitic acid is more strongly associated with mitochondrial fragmentation, increased oxidative metabolism, and ROS formation in both the cytosol and mitochondria.

    “Oleic acid primarily promotes the formation of larger lipid droplets and facilitates the safe esterification of fatty acids into triglycerides [148,149,150,151], whereas palmitic acid is more strongly associated with mitochondrial fragmentation, increased oxidative metabolism, and ROS formation in both the cytosol and mitochondria.”

    From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [149]

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References 52 · Cited by 125

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Authors
Eynaudi, A., Díaz-Castro, F., Bórquez, J. C., Bravo-Sagua, R., Parra, V., & Troncoso, R.
Affiliations
  • University of Chile (CL)
  • Advanced Center for Chronic Diseases (CL)
Corresponding author
  • Parra, Valentina
  • Troncoso, Rodrigo
ORCID
Venue
Frontiers in Nutrition
Publisher
Frontiers Media SA
Published
2021-11-12
Volume
8
Pages
775382-775382
ISSN
2296-861X (ISSN-L)
DOI
10.3389/fnut.2021.775382
PMC
PMC8632770
OpenAlex
W3212156223
Cited by
125
References
52
Citations by year
2026: 32 · 2025: 29 · 2024: 39 · 2023: 16 · 2022: 9
FWCI
6.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Nutrition (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Universidad de Chile (submittedVersion, cc-by-nc-nd)
Funders
Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
oleic acid, palmitic acid, lipid droplets, mitochondria, fatty acid overload, mitochondrial fragmentation, mitochondrial respiration, mitochondrial membrane potential, ATP production, fatty acid oxidation, triglyceride accumulation, hepatic steatosis, liver injury, HepG2 cells

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