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The interplay between non-esterified fatty acids and plasma zinc and its influence on thrombotic risk in obesity and type 2 diabetes
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Hierons, Stephen J., Marsh, Jordan S., Wu, Dongmei, Blindauer, Claudia A. and Stewart, Alan J. (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 (18). 10140. doi:10.3390/ijms221810140 ISSN 1422-0067.
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Official URL: https://doi.org/10.3390/ijms221810140
Abstract
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 Zn speciation in the plasma. Zn 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 Zn , thus increasing the ion's availability to bind and activate coagulation proteins. NEFA-mediated perturbation of HSA-Zn binding is thus predicted to contribute to the prothrombotic milieu in obesity and T2DM, representing a novel targetable disease mechanism in these disorders.
| Item Type: | Journal Article | |||||||||||||||
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| Subjects: | R Medicine > RC Internal medicine | |||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | |||||||||||||||
| SWORD Depositor: | Library Publications Router | |||||||||||||||
| Library of Congress Subject Headings (LCSH): | Type 2 diabetes -- Complications, Zinc, Zinc in the body, Obesity, Thrombosis -- Risk factors, Fatty acids, Serum albumin, Insulin resistance | |||||||||||||||
| Journal or Publication Title: | International Journal of Molecular Sciences | |||||||||||||||
| Publisher: | M D P I AG | |||||||||||||||
| ISSN: | 1422-0067 | |||||||||||||||
| Official Date: | 20 September 2021 | |||||||||||||||
| Dates: |
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| Volume: | 22 | |||||||||||||||
| Number: | 18 | |||||||||||||||
| Article Number: | 10140 | |||||||||||||||
| DOI: | 10.3390/ijms221810140 | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||
| Date of first compliant deposit: | 29 June 2022 | |||||||||||||||
| Date of first compliant Open Access: | 29 June 2022 | |||||||||||||||
| RIOXX Funder/Project Grant: |
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