Fatty Acid Transport Mechanisms in Metabolic Disorders

Fatty acids serve as key energy substrates and signalling molecules in human physiology. Their cellular uptake is mediated by a combination of passive diffusion of micellar complexes and protein-facilitated transport across the plasma membrane. Integral membrane transporters, most notably the fatty acid transport proteins (FATP) family and the scavenger receptor CD36, mediate the binding and translocation of long-chain fatty acids, often coupling uptake to intracellular activation by acyl-CoA synthetases. Once inside the cell, fatty acids may be channelled towards storage as triglycerides, oxidation in mitochondria via the carnitine palmitoyltransferase system, or incorporation into membrane phospholipids. In metabolic disorders such as non-alcoholic fatty liver disease, obesity and type 2 diabetes, the expression and activity of transporters and enzymes become dysregulated, driving ectopic lipid accumulation, lipotoxic stress and insulin resistance. Tissue-specific isoforms of FATP and CD36, as well as regulatory kinases and phosphatases, together dictate the rate and selectivity of fatty acid entry into hepatocytes, myocytes and adipocytes. A deeper understanding of these pathways underpins the development of targeted therapies aimed at restoring lipid homeostasis and mitigating the global burden of metabolic disease.

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Fatty Acid Transport Mechanisms in Metabolic Disorders publication trend

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Technical terms

Fatty acid transport protein (FATP): A family of integral membrane proteins that facilitate the uptake of long-chain fatty acids and often possess intrinsic acyl-CoA synthetase activity.

CD36 (fatty acid translocase): A cell-surface glycoprotein that binds long-chain fatty acids, facilitating their passage into the cytosol.

Acyl-CoA synthetase: An enzyme that catalyses the ATP-dependent conversion of free fatty acids into fatty acyl-CoA thioesters, a prerequisite for intracellular metabolism.

Protein tyrosine phosphatase 4A1 (PTP4A1): An enzyme that dephosphorylates signalling molecules, thereby modulating the expression and trafficking of nutrient transporters in liver cells.

References

1. Hepatic PTP4A1 ameliorates high-fat diet-induced hepatosteatosis and hyperglycemia by the activation of the CREBH/FGF21 axis. Theranostics (2023).
2. AI-Based Homology Modelling of Fatty Acid Transport Protein 1 Using AlphaFold: Structural Elucidation and Molecular Dynamics Exploration. Biomolecules (2023).