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Updated: Aug 5, 2026
07:03
In Vitro Modeling of Fat Deposition in Metabolic Dysfunction-Associated Steatotic Liver Disease
Published on: July 19, 2024
Lactate Aggravates MASLD via PPARγ/CD36-Mediated Hepatocellular Fatty Acid Uptake
Wenke Sun1, Weiwei Li1, Guangyi Ouyang1
1College of Animal Science and Medicine, Shenyang Agricultural University, No. 120, Dongling Road, Shenyang 110866, China.
Cells
|July 27, 2026
Summary
Lactate buildup exacerbates liver fat accumulation in metabolic dysfunction-associated steatotic liver disease (MASLD) by upregulating the PPARγ/CD36 pathway. Inhibiting this pathway can reduce hepatic steatosis, suggesting a therapeutic target for MASLD progression.
Area of Science:
- Hepatology
- Metabolic Diseases
- Molecular Biology
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health concern characterized by excessive liver fat accumulation.
- Hepatocellular injury in MASLD impairs lactate clearance, leading to increased lactate levels in the liver microenvironment.
- The precise role of lactate in worsening liver lipid metabolism and driving MASLD progression is not fully understood.
Purpose of the Study:
- To investigate the causal role of lactate in hepatic lipid metabolism dysfunction in MASLD.
- To identify molecular targets and pathways through which lactate influences liver steatosis.
- To evaluate the therapeutic potential of targeting lactate-related pathways in MASLD.
Main Methods:
- Bioinformatic analysis of transcriptomic datasets (GEO database) to assess lactate dehydrogenase (LDH) expression in MASLD.
- Network pharmacology to predict molecular targets of lactate, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
- Molecular docking, molecular dynamics simulations, and in vivo/in vitro experiments using liver-specific Ldha knockdown mice and hepatocytes to validate findings.
Main Results:
- Lactate dehydrogenase (LDH) expression was significantly upregulated in MASLD liver tissues.
- Exogenous lactate administration increased hepatic lipid accumulation, triglyceride levels, and lipid droplet formation in MASLD models.
- Lactate exposure upregulated the expression of PPARγ and CD36, key regulators of lipid metabolism.
- Inhibition of lactate production or silencing of PPARγ/CD36 attenuated lipid accumulation.
Conclusions:
- Lactate exposure is linked to increased hepatic lipid accumulation via the upregulation of the PPARγ/CD36 axis.
- Targeting the PPARγ/CD36 pathway can mitigate lactate-associated hepatic steatosis.
- This pathway represents a potential therapeutic strategy to slow MASLD progression.
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