Metabolic Regulation of Hepatic Lipid Homeostasis

The liver orchestrates systemic lipid balance through tightly regulated pathways of uptake, synthesis, storage and oxidation. Fatty acids are imported into hepatocytes via specialised transporters and are either esterified into triglycerides for storage or channelled into mitochondrial β-oxidation to generate energy. Key signalling nodes—including AMP-activated protein kinase (AMPK), sterol regulatory element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor-α (PPARα)—act as metabolic sensors that respond to nutritional and hormonal cues. When energy levels are low, AMPK activation inhibits lipogenesis and stimulates fatty acid oxidation, whereas SREBP-1c drives de novo lipid synthesis under nutrient-rich conditions. Transcription factors such as FOXA1 and epigenetic regulators like Sirtuin 6 integrate post-translational modifications—SUMOylation and ubiquitination—to fine-tune gene expression governing lipid flux. Dysregulation of any component in this network can precipitate hepatic steatosis, non-alcoholic fatty liver disease and associated cardiometabolic disorders. Emerging research highlights cross-talk between endoplasmic reticulum stress, autophagy and inflammatory pathways, underscoring the complex interplay that maintains hepatic lipid homeostasis and its vulnerability to dietary and pharmacological perturbation.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Metabolic Regulation of Hepatic Lipid Homeostasis publication trend

The graph below shows the total number of articles in metabolic regulation of hepatic lipid homeostasis across all publications each year (not limited to Nature Index journals).

Technical terms

Hepatic steatosis: Excessive accumulation of lipid droplets within liver cells.

AMP-activated protein kinase (AMPK): Cellular energy sensor that shifts metabolism from anabolism to catabolism.

Lipogenesis: Enzymatic process converting acetyl-CoA into fatty acids and triglycerides.

SREBP-1c: Transcription factor that up-regulates genes for fatty acid and triglyceride synthesis.

PPARα: Nuclear receptor that enhances expression of genes involved in fatty acid oxidation.

DeSUMOylation: Removal of SUMO modifiers from proteins, altering their stability and function.

Ubiquitination: Attachment of ubiquitin molecules to a protein, targeting it for proteasomal degradation.

Sirtuin 6 (Sirt6): NAD⁺-dependent deacetylase that regulates glucose and lipid metabolism.

References

1. Impaired SUMOylation of FoxA1 promotes nonalcoholic fatty liver disease through down-regulation of Sirt6. Cell Death & Disease (2024).
2. Non-Alcoholic Fatty Liver Disease (NAFLD) Pathogenesis and Natural Products for Prevention and Treatment. International Journal of Molecular Sciences (2022).
3. Activation of AMP‐activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders. The Journal of Physiology (2006).