Lipid Metabolism and Liver Disease Mechanisms

Lipid metabolism in the liver encompasses the coordinated processes of fatty acid uptake, synthesis, storage, oxidation and export. Under physiological conditions, circulating free fatty acids are taken up by hepatocytes through transport proteins and esterified into triglycerides for temporary storage or packaged into very low-density lipoproteins for secretion. Concurrently, excess carbohydrates drive de novo lipogenesis via transcriptional programmes controlled by sterol regulatory element-binding proteins and peroxisome proliferator-activated receptors. Fatty acids may also undergo β-oxidation in mitochondria and peroxisomes to generate energy. Disruption of this balance—through overnutrition, insulin resistance or genetic predisposition—leads to accumulation of lipid droplets, oxidative and endoplasmic reticulum stress, lipotoxicity and activation of inflammatory and fibrotic pathways. This spectrum of injury, ranging from simple steatosis to steatohepatitis and cirrhosis, underpins the global burden of non-alcoholic fatty liver disease and metabolic-associated steatohepatitis. Recent advances have elucidated novel kinases, transcription factors and cellular clearance mechanisms as key nodes in steatosis progression, informing potential therapeutic strategies and biomarker development.

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Lipid Metabolism and Liver Disease Mechanisms publication trend

The graph below shows the total number of articles in lipid metabolism and liver disease mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Non-alcoholic fatty liver disease (NAFLD): A spectrum of liver disorders characterised by excess hepatic lipid accumulation in the absence of significant alcohol intake.

Lipotoxicity: Cellular injury resulting from the accumulation of toxic lipid species that exceed the organelle and antioxidant capacity of hepatocytes.

De novo lipogenesis (DNL): Metabolic pathway by which the liver converts excess carbohydrates into fatty acids for storage or further processing.

Peroxisome proliferator-activated receptor γ (PPARγ): A nuclear receptor that regulates genes involved in adipogenesis, lipid uptake and glucose metabolism.

Betaine-homocysteine S-methyltransferase 1 (BHMT1): An enzyme that catalyses homocysteine remethylation and influences transcription factors controlling lipid synthesis.

Autophagy: Intracellular degradation process in which damaged organelles and lipid droplets are engulfed and recycled to maintain cellular homeostasis.

References

1. Ribosomal modification protein rimK-like family member A activates betaine-homocysteine S-methyltransferase 1 to ameliorate hepatic steatosis. Signal Transduction and Targeted Therapy (2024).
2. Naringenin cationic lipid-modified nanoparticles mitigate MASLD progression by modulating lipid homeostasis and gut microbiota. Journal of Nanobiotechnology (2025).
3. IRF8 aggravates nonalcoholic fatty liver disease via BMAL1/PPARγ axis. Genes & Diseases (2024).
4. NAFLD: Mechanisms, Treatments, and Biomarkers. Biomolecules (2022).