Mitochondrial Metabolism of Fatty Acids in Hepatic Systems

The liver orchestrates systemic energy balance through the mitochondrial breakdown of long-chain fatty acids. Uptake by hepatocytes is followed by activation to acyl-CoA and transport across the inner mitochondrial membrane via the carnitine shuttle. Within the matrix, sequential cycles of β-oxidation cleave two-carbon units, yielding acetyl-CoA for entry into the tricarboxylic acid cycle and subsequent ATP generation via oxidative phosphorylation. This process is tightly regulated by nuclear receptors and co-activators, notably PPARα and PGC-1α, and is modulated by nutrient status, hormonal signals and post-translational modifications such as protein deacetylation. Crosstalk with peroxisomal oxidation complements mitochondrial capacity, especially for very-long-chain substrates. Perturbation of this network contributes to hepatic steatosis, insulin resistance and non-alcoholic fatty liver disease, while plasma acylcarnitine profiles serve as sensitive indicators of mitochondrial function. Therapeutic strategies targeting mitochondrial β-oxidation hold promise for metabolic disorders and cardiovascular risk reduction.

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Mitochondrial Metabolism of Fatty Acids in Hepatic Systems publication trend

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

Technical terms

β-oxidation: Sequential enzymatic breakdown of fatty acyl-CoA in mitochondria, releasing acetyl-CoA and reducing equivalents.
Acylcarnitine: Esterified fatty acid intermediate formed for transport of long-chain acyl groups across the mitochondrial membrane.
PPARα: Peroxisome proliferator-activated receptor alpha; nuclear transcription factor that governs genes of fatty acid transport and oxidation.
VLDL: Very-low-density lipoprotein; hepatic lipoprotein responsible for exporting endogenous triglycerides to peripheral tissues.

References

1. Associations between fatty acid oxidation, hepatic mitochondrial function, and plasma acylcarnitine levels in mice. Nutrition & Metabolism (2018).
2. Exposure to Plasma From Non-alcoholic Fatty Liver Disease Patients Affects Hepatocyte Viability, Generates Mitochondrial Dysfunction, and Modulates Pathways Involved in Fat Accumulation and Inflammation. Frontiers in Medicine (2021).
3. Bromelain Confers Protection Against the Non-Alcoholic Fatty Liver Disease in Male C57BL/6 Mice. Nutrients (2020).
4. A mitochondria-targeted fatty acid analogue influences hepatic glucose metabolism and reduces the plasma insulin/glucose ratio in male Wistar rats. PLOS ONE (2019).