Distinct OA:PA Ratios Generate Discrete Hepatocellular Phenotypes in HepG2 Cells.
- 1Center for Bio-Imaging & Translational Research, Korea Basic Science Institute, Cheongju 28119, Republic of Korea.
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by hepatic steatosis, metabolic stress, and inflammation. Although free fatty acid (FFA)-based in vitro models are widely used, how OA:PA ratios shape hepatocellular phenotypes remains incompletely characterized. HepG2 cells were treated with oleic acid (OA), palmitic acid (PA), or four OA:PA mixtures (O1P1, O2P1, O3P2, O1P2) for 24 or 48 h. OA and OA:PA mixtures were evaluated at 500 μM total FFA (O2P1: 333.3 μM OA + 166.7 μM PA; O3P2: 300 μM OA + 200 μM PA), whereas PA alone was evaluated at 200 μM. Cell viability, lipid accumulation, ultrastructure, oxidative response, secreted cytokines, and molecular responses were evaluated. Distinct OA:PA ratios generated discrete hepatocellular states rather than a linear steatosis-to-lipotoxicity continuum. O3P2 produced a steatosis-dominant phenotype with pronounced lipid accumulation and relatively limited stress signaling. In contrast, O2P1 combined substantial lipid accumulation with elevated DCF fluorescence, AMP-activated protein kinase (AMPK) phosphorylation, nuclear factor kappa B (NF-κB)-associated inflammatory signaling, and interleukin-8 (IL-8) secretion, representing a pronounced stress-responsive phenotype with selected MASH-relevant features. Selected responses were also evaluated in SNU-449 cells, revealing cell-line-specific patterns. Collectively, these findings support a phenotype-oriented framework for OA:PA ratio selection in hepatocyte-based in vitro MASH modeling.
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BibTeX
@article{jeong2026distinct,
title = {{Distinct OA:PA Ratios Generate Discrete Hepatocellular Phenotypes in HepG2 Cells.}},
author = {Hangyeon Jeong and Yesol Han and Jiyeong Park and Hanbyul Noh and Eunyoung Moon and Yanghoon Huh},
journal = {Cells},
year = {2026},
month = sep,
doi = {10.3390/cells15191774},
url = {https://europepmc.org/article/MED/42882471},
note = {CC BY},
}
RIS
TY - JOUR
TI - Distinct OA:PA Ratios Generate Discrete Hepatocellular Phenotypes in HepG2 Cells.
AU - Hangyeon Jeong
AU - Yesol Han
AU - Jiyeong Park
AU - Hanbyul Noh
AU - Eunyoung Moon
AU - Yanghoon Huh
PY - 2026
DA - 2026/09/29
JO - Cells
DO - 10.3390/cells15191774
UR - https://europepmc.org/article/MED/42882471
AB - Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by hepatic steatosis, metabolic stress, and inflammation. Although free fatty acid (FFA)-based in vitro models are widely used, how OA:PA ratios shape hepatocellular phenotypes remains incompletely characterized. HepG2 cells were treated with oleic acid (OA), palmitic acid (PA), or four OA:PA mixtures (O1P1, O2P1, O3P2, O1P2) for 24 or 48 h. OA and OA:PA mixtures were evaluated at 500 μM total FFA (O2P1: 333.3 μM OA + 166.7 μM PA; O3P2: 300 μM OA + 200 μM PA), whereas PA alone was evaluated at 200 μM. Cell viability, lipid accumulation, ultrastructure, oxidative response, secreted cytokines, and molecular responses were evaluated. Distinct OA:PA ratios generated discrete hepatocellular states rather than a linear steatosis-to-lipotoxicity continuum. O3P2 produced a steatosis-dominant phenotype with pronounced lipid accumulation and relatively limited stress signaling. In contrast, O2P1 combined substantial lipid accumulation with elevated DCF fluorescence, AMP-activated protein kinase (AMPK) phosphorylation, nuclear factor kappa B (NF-κB)-associated inflammatory signaling, and interleukin-8 (IL-8) secretion, representing a pronounced stress-responsive phenotype with selected MASH-relevant features. Selected responses were also evaluated in SNU-449 cells, revealing cell-line-specific patterns. Collectively, these findings support a phenotype-oriented framework for OA:PA ratio selection in hepatocyte-based in vitro MASH modeling.
SN - 2073-4409
ER -