Free Fatty Acids in Vascular Dysfunction and Metabolic Disorders
Summary
Free fatty acids (FFAs) are non-esterified fatty acid molecules circulating in plasma, released primarily through adipose tissue lipolysis. Under physiological conditions, they serve as essential energy substrates and signalling mediators. However, chronically elevated FFAs, as observed in obesity, insulin resistance and type 2 diabetes, promote vascular dysfunction and contribute to the pathogenesis of atherosclerosis, hypertension and other cardiometabolic disorders. Excessive FFAs impair endothelial insulin signalling and reduce nitric oxide bioavailability, leading to endothelial dysfunction, a key early event in vascular disease. They also induce oxidative stress, inflammatory activation and lipotoxic injury in endothelial and smooth muscle cells. Complementary alterations in lipid-sensing transcription factors and FFA-activated G protein-coupled receptors further exacerbate dysregulated vascular homeostasis. The global burden of cardiometabolic disease highlights the need to translate mechanistic insights into therapeutic strategies that normalise FFA handling, reduce oxidative and inflammatory injury, and restore endothelial integrity.
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Free Fatty Acids in Vascular Dysfunction and Metabolic Disorders publication trend
The graph below shows the total number of articles in free fatty acids in vascular dysfunction and metabolic disorders across all publications each year (not limited to Nature Index journals).
Technical terms
Free fatty acids (FFAs): Non-esterified fatty acids released from adipose tissue, serving as both energy substrates and signalling molecules.
Endothelial dysfunction: Impaired vasodilatory response of the vascular endothelium, often due to reduced nitric oxide production and heightened oxidative stress.
Lipotoxicity: Cellular injury caused by accumulation of lipid intermediates and excessive FFAs leading to organelle dysfunction and apoptosis.
Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen metabolism that can damage proteins, lipids and DNA when produced in excess.
AMP-activated protein kinase (AMPK): A cellular energy sensor activated by rising AMP : ATP ratios that promotes catabolic pathways and mitigates metabolic stress.
Nitric oxide (NO): A gaseous signalling molecule synthesised by endothelial nitric oxide synthase, crucial for vasodilation and vascular homeostasis.
References
- Role of free fatty acids in endothelial dysfunction. Journal of Biomedical Science (2017).
- AICAR Protects Vascular Endothelial Cells from Oxidative Injury Induced by the Long-Term Palmitate Excess. International Journal of Molecular Sciences (2021).
- In Vitro Modeling of Diabetes Impact on Vascular Endothelium: Are Essentials Engaged to Tune Metabolism?. Biomedicines (2022).
- Association of plasma free fatty acids levels with the presence and severity of coronary and carotid atherosclerotic plaque in patients with type 2 diabetes mellitus. BMC Endocrine Disorders (2020).
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