Lysine-proline-valine peptide attenuates hepatic lipid accumulation through ROS-dependent regulation of the PPARγ pathway in HepG2 cells. — VialBase Research
KPV curbs fat accumulation in liver cells by acting as an antioxidant that dials down ROS/ERK and AKT-mTORC1-PPARγ lipogenic signaling, a first in vitro signal of relevance to non-alcoholic fatty liver disease.
- Oleic acid (OA) markedly increased hepatic lipid deposition in HepG2 cells by upregulating fatty acid synthase (FAS).
- KPV at 100 µg/mL significantly attenuated OA-induced lipid accumulation and suppressed FAS expression without inducing cytotoxicity.
- KPV reduced ROS generation, thereby preventing activation of ERK.
- KPV downregulated AKT phosphorylation, leading to inhibition of mTORC1 phosphorylation under hepatic steatosis conditions.
- KPV regulated phosphorylation of PPARγ, a key de novo lipogenesis transcription factor, normalizing FAS expression.
Summary
This in vitro study examined whether Lysine-Proline-Valine (KPV), an endogenous tripeptide derived from α-melanocyte-stimulating hormone, protects hepatic HepG2 cells against oleic acid (OA)-induced oxidative damage and lipid accumulation, a model of the hepatocellular steatosis seen early in non-alcoholic fatty liver disease. OA drove lipid deposition by upregulating fatty acid synthase (FAS), while KPV at 100 µg/mL blunted this accumulation and suppressed FAS without cytotoxicity. Mechanistically, KPV lowered ROS, preventing ERK activation, and downregulated AKT-mTORC1 and PPARγ signaling to normalize lipogenesis.
Key Findings
- Oleic acid (OA) treatment markedly enhanced hepatic lipid deposition by upregulating fatty acid synthase (FAS) expression.
- KPV at 100 µg/mL significantly attenuated OA-induced lipid accumulation and suppressed FAS expression without inducing cytotoxicity.
- KPV reduced reactive oxygen species generation, thereby preventing activation of ERK.
- KPV downregulated AKT phosphorylation, leading to inhibition of mTORC1 phosphorylation under hepatic steatosis conditions.
- KPV regulated the phosphorylation of PPARγ, a key transcription factor in de novo lipogenesis, thereby normalizing FAS expression.
Relevance to KPV
This is an early, mechanistic look at KPV in a metabolic context, extending its documented anti-inflammatory and antioxidant activity into hepatic lipid handling. By tracing KPV’s effect through ROS to the ERK, AKT-mTORC1, and PPARγ lipogenic axes, the study frames the tripeptide as an antioxidant regulator of fat synthesis rather than a direct lipid-lowering drug. The results are confined to a single hepatocyte cell line under an oleic-acid challenge, so they establish plausibility for a fatty-liver application without demonstrating efficacy in vivo or in humans.
Citation
Lee JY, Lee J, Jung WK, et al. Lysine-proline-valine peptide attenuates hepatic lipid accumulation through ROS-dependent regulation of the PPARγ pathway in HepG2 cells. Cytotechnology. 2026. doi:10.1007/s10616-026-00967-z.
See Also
- Parent compound: KPV
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