Fatty acid oxidation, the process of breaking down fats for energy, is a tightly regulated process crucial for energy homeostasis. Regulation occurs at multiple levels, involving various factors and pathways.
Key Regulatory Mechanisms
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Peroxisome Proliferator-Activated Receptor-alpha (PPAR-α): This nuclear receptor plays a central role. A disruption in PPAR-α or fatty acid oxidation itself reduces the body's ability to use fats for energy, leading to fat accumulation (steatosis) [94].
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Pyruvate Dehydrogenase Complex (PDHc): This enzyme complex regulates the metabolic flow from carbohydrates to fatty acid oxidation. By controlling the conversion of pyruvate to acetyl-CoA, it influences the availability of substrates for fatty acid breakdown [ScienceDirect Topics].
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Carbohydrate Metabolism: Fatty acid oxidation is directly influenced by carbohydrate metabolism. Increased glycolytic flux (the breakdown of glucose) directly inhibits long-chain fatty acid oxidation during exercise [pubmed.ncbi.nlm.nih.gov/9277379/]. Furthermore, glucose controls glucagon secretion by regulating fatty acid oxidation in pancreatic α-cells, impacting whole-body glucose homeostasis [diabetesjournals.org/diabetes/article/72/10/1446/153439/].
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Other Regulatory Pathways: Additional pathways modulate fatty acid oxidation, including a PML–PPAR-δ pathway influencing hematopoietic stem cell function [nature.com/articles/nm.2882], and the impact of fatty acid oxidation on cellular senescence via the autophagy-SIRT1 axis [bmbreports.org/journal/view.html?doi=10.5483/BMBRep.2023-0076]. CD36, a fatty acid transporter and signaling receptor, also plays a regulatory role [rupress.org/jem/article/219/6/e20211314/213166/].
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Exercise: During exercise, regulation of fatty acid metabolism is complex, with limitations in fatty acid oxidation influencing overall energy production [pmc.ncbi.nlm.nih.gov/articles/PMC3381814/].
Factors Affecting Regulation
The expression of genes involved in mitochondrial fatty acid β-oxidation (FAO) can be altered in conditions like heart failure [ahajournals.org/doi/10.1161/01.CIR.94.11.2837]. Furthermore, fatty acids themselves, derived from the diet and metabolic pathways, regulate hepatic gene transcription [pmc.ncbi.nlm.nih.gov/articles/PMC3940310/].
