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Review

The Interplay between Non-Esterified Fatty Acids and Plasma Zinc and Its Influence on Thrombotic Risk in Obesity and Type 2 Diabetes

1
School of Medicine, University of St. Andrews, St. Andrews KY16 9TF, Fife, UK
2
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
*
Author to whom correspondence should be addressed.
Academic Editors: Jean-François Tanti and Ramzi Ajjan
Int. J. Mol. Sci. 2021, 22(18), 10140; https://doi.org/10.3390/ijms221810140
Received: 30 August 2021 / Revised: 13 September 2021 / Accepted: 16 September 2021 / Published: 20 September 2021
(This article belongs to the Special Issue Molecular Pathways for Vascular Risk in Diabetes)
Thrombosis is a major comorbidity of obesity and type-2 diabetes mellitus (T2DM). Despite the development of numerous effective treatments and preventative strategies to address thrombotic disease in such individuals, the incidence of thrombotic complications remains high. This suggests that not all the pathophysiological mechanisms underlying these events have been identified or targeted. Non-esterified fatty acids (NEFAs) are increasingly regarded as a nexus between obesity, insulin resistance, and vascular disease. Notably, plasma NEFA levels are consistently elevated in obesity and T2DM and may impact hemostasis in several ways. A potentially unrecognized route of NEFA-mediated thrombotic activity is their ability to disturb Zn2+ speciation in the plasma. Zn2+ is a potent regulator of coagulation and its availability in the plasma is monitored carefully through buffering by human serum albumin (HSA). The binding of long-chain NEFAs such as palmitate and stearate, however, trigger a conformational change in HSA that reduces its ability to bind Zn2+, thus increasing the ion’s availability to bind and activate coagulation proteins. NEFA-mediated perturbation of HSA-Zn2+ binding is thus predicted to contribute to the prothrombotic milieu in obesity and T2DM, representing a novel targetable disease mechanism in these disorders. View Full-Text
Keywords: diabetes; human serum albumin; insulin resistance; non-esterified fatty acids; obesity; thrombosis; zinc diabetes; human serum albumin; insulin resistance; non-esterified fatty acids; obesity; thrombosis; zinc
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MDPI and ACS Style

Hierons, S.J.; Marsh, J.S.; Wu, D.; Blindauer, C.A.; Stewart, A.J. The Interplay between Non-Esterified Fatty Acids and Plasma Zinc and Its Influence on Thrombotic Risk in Obesity and Type 2 Diabetes. Int. J. Mol. Sci. 2021, 22, 10140. https://doi.org/10.3390/ijms221810140

AMA Style

Hierons SJ, Marsh JS, Wu D, Blindauer CA, Stewart AJ. The Interplay between Non-Esterified Fatty Acids and Plasma Zinc and Its Influence on Thrombotic Risk in Obesity and Type 2 Diabetes. International Journal of Molecular Sciences. 2021; 22(18):10140. https://doi.org/10.3390/ijms221810140

Chicago/Turabian Style

Hierons, Stephen J., Jordan S. Marsh, Dongmei Wu, Claudia A. Blindauer, and Alan J. Stewart 2021. "The Interplay between Non-Esterified Fatty Acids and Plasma Zinc and Its Influence on Thrombotic Risk in Obesity and Type 2 Diabetes" International Journal of Molecular Sciences 22, no. 18: 10140. https://doi.org/10.3390/ijms221810140

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