Lipid Metabolism in Hepatic Dysfunction

The liver is central to whole‐body lipid homeostasis, orchestrating the uptake, synthesis, storage and export of fatty acids and their derivatives. Under normal conditions, hepatocytes synthesise triglycerides for storage in lipid droplets or package them into very low‐density lipoproteins (VLDL) for secretion. Dysregulation of these pathways contributes to hepatic steatosis, inflammation and progression to fibrosis in disorders such as non‐alcoholic fatty liver disease (NAFLD). Enhanced de novo lipogenesis driven by transcription factors such as sterol regulatory element‐binding proteins (SREBPs), coupled with impaired fatty acid oxidation and defective VLDL assembly, leads to lipid accumulation within hepatocytes. Excess lipid induces mitochondrial dysfunction and oxidative stress, activating inflammatory responses and cell death pathways. Furthermore, alterations in lipoprotein export and quality control mechanisms of apolipoprotein B (apoB) determine hepatic triglyceride burden and systemic lipid levels. Collectively, disturbances in hepatic lipid flux underpin the pathogenesis of metabolic and viral liver diseases, highlighting targets for therapeutic intervention. Understanding the molecular regulators of lipid droplet dynamics, intracellular trafficking of lipoproteins and transcriptional networks that balance lipid synthesis and catabolism remains a priority for combating global liver disease.

Research from Nature Portfolio

Recent studies have revealed a pivotal role for the RNA‐binding protein HuR in coordinating hepatic lipid transport and mitochondrial bioenergetics. In models of high‐fat diet‐induced steatosis, HuR interacts with key transcripts encoding Apob and components of the respiratory chain to modulate both VLDL assembly and ATP synthesis. Hepatocyte‐specific deletion of HuR diminishes apoB production and mitochondrial function, exacerbating steatosis, while re‐expression of HuR restores lipid export and energy homeostasis. This work establishes post‐transcriptional control by HuR as a fundamental mechanism linking lipid droplet clearance to mitochondrial health in liver disease.

Lipid Metabolism in Hepatic Dysfunction publication trend

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

Technical terms

Lipid droplets: Intracellular organelles storing neutral lipids such as triglycerides and cholesterol esters.

Very low‐density lipoproteins (VLDL): Hepatic lipoprotein particles that transport triglycerides and cholesterol to peripheral tissues.

Apolipoprotein B (apoB): Structural protein essential for VLDL assembly and secretion by hepatocytes.

HuR (ELAVL1): Ubiquitous RNA‐binding protein that binds target mRNAs to regulate their stability and translation.

Non‐alcoholic fatty liver disease (NAFLD): Spectrum of hepatic lipid accumulation not caused by excessive alcohol intake, ranging from steatosis to cirrhosis.

References

1. MCD Diet Modulates HuR and Oxidative Stress-Related HuR Targets in Rats. International Journal of Molecular Sciences (2023).
2. Hepatic HuR modulates lipid homeostasis in response to high-fat diet. Nature Communications (2020).
3. Effect of Octreotide on Hepatic Steatosis in Diet-Induced Obesity in Rats. PLOS ONE (2016).
4. Unveiling the Multifaceted Role of CIDEB: From Apoptosis to Lipid Metabolism and Liver Health. Livers (2024).
5. Apolipoprotein B100 quality control and the regulation of hepatic very low density lipoprotein secretion. Journal of Biomedical Research (2014).