Hepatic Lipid Metabolism in Metabolic Disorders

The liver occupies a pivotal role in whole-body energy homeostasis by coordinating the uptake, synthesis, oxidation, storage and secretion of lipids. Under normal conditions, free fatty acids derived from adipose tissue lipolysis and dietary sources are esterified into triacylglycerol and either stored in lipid droplets or packaged into very low-density lipoproteins (VLDL) for export. Concurrently, de novo lipogenesis converts excess carbohydrates and amino acids into fatty acids, while mitochondrial β-oxidation and peroxisomal pathways ensure the degradation of surplus lipids. In metabolic disorders such as obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), nutrient overabundance, insulin resistance and chronic inflammation shift hepatic lipid flux towards enhanced lipogenesis and storage, while impairing oxidative and secretory pathways. The resulting hepatic steatosis can progress to steatohepatitis, fibrosis and cirrhosis, contributing to systemic dyslipidaemia and cardiometabolic risk. Recent advances have highlighted the importance of substrate selection, hormonal and neural regulation, and interorgan crosstalk in shaping hepatic lipid dynamics. Nutritional interventions, enzyme-targeted therapeutics and strategies to boost lipid export offer promising avenues to correct hepatic lipid imbalance and mitigate the global burden of metabolic disease.

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Hepatic Lipid Metabolism in Metabolic Disorders publication trend

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Technical terms

De novo lipogenesis (DNL): The synthesis of fatty acids from non-lipid precursors such as carbohydrates or amino acids within hepatocytes.

Triacylglycerol (TG): The principal storage form of fat, comprising three fatty acids esterified to a glycerol backbone.

Very low-density lipoprotein (VLDL): Lipoprotein particles synthesised by the liver to transport triglycerides and cholesterol to peripheral tissues.

Hepatic steatosis: The excessive accumulation of fat within liver cells, commonly referred to as fatty liver.

β-oxidation: The mitochondrial enzymatic process that breaks down fatty acids into acetyl-CoA units for ATP generation.

References

1. Amino acid is a major carbon source for hepatic lipogenesis. Cell Metabolism (2024).
2. Leptin acutely increases hepatic triglyceride secretion in patients with lipodystrophy. Metabolism (2025).
3. Dietary Regulation of Hepatic Triacylglycerol Content—the Role of Eucaloric Carbohydrate Restriction with Fat or Protein Replacement. Advances in Nutrition (2023).