PMID- 34576303
OWN - NLM
STAT- MEDLINE
DCOM- 20211018
LR  - 20211018
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 18
DP  - 2021 Sep 20
TI  - The Interplay between Non-Esterified Fatty Acids and Plasma Zinc and Its 
      Influence on Thrombotic Risk in Obesity and Type 2 Diabetes.
LID - 10.3390/ijms221810140 [doi]
LID - 10140
AB  - 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(2+) speciation in the plasma. Zn(2+) 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(2+), thus 
      increasing the ion's availability to bind and activate coagulation proteins. 
      NEFA-mediated perturbation of HSA-Zn(2+) binding is thus predicted to contribute 
      to the prothrombotic milieu in obesity and T2DM, representing a novel targetable 
      disease mechanism in these disorders.
FAU - Hierons, Stephen J
AU  - Hierons SJ
AD  - School of Medicine, University of St. Andrews, St. Andrews KY16 9TF, Fife, UK.
FAU - Marsh, Jordan S
AU  - Marsh JS
AD  - School of Medicine, University of St. Andrews, St. Andrews KY16 9TF, Fife, UK.
FAU - Wu, Dongmei
AU  - Wu D
AD  - School of Medicine, University of St. Andrews, St. Andrews KY16 9TF, Fife, UK.
FAU - Blindauer, Claudia A
AU  - Blindauer CA
AUID- ORCID: 0000-0001-8396-9332
AD  - Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
FAU - Stewart, Alan J
AU  - Stewart AJ
AUID- ORCID: 0000-0003-4580-1840
AD  - School of Medicine, University of St. Andrews, St. Andrews KY16 9TF, Fife, UK.
LA  - eng
GR  - FS/20/3/34956/BHF_/British Heart Foundation/United Kingdom
GR  - FS/19/69/34639/BHF_/British Heart Foundation/United Kingdom
GR  - N/A/China Scholarship Council/
PT  - Journal Article
PT  - Review
DEP - 20210920
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Fatty Acids, Nonesterified)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/blood/epidemiology/*metabolism
MH  - Fatty Acids, Nonesterified/*blood/metabolism
MH  - Humans
MH  - Obesity/blood/epidemiology/*metabolism
MH  - Thrombosis/blood/epidemiology/*metabolism
MH  - Zinc/*blood/metabolism
PMC - PMC8471329
OTO - NOTNLM
OT  - diabetes
OT  - human serum albumin
OT  - insulin resistance
OT  - non-esterified fatty acids
OT  - obesity
OT  - thrombosis
OT  - zinc
COIS- The authors declare no conflict of interest.
EDAT- 2021/09/29 06:00
MHDA- 2021/10/21 06:00
PMCR- 2021/09/20
CRDT- 2021/09/28 01:19
PHST- 2021/08/30 00:00 [received]
PHST- 2021/09/13 00:00 [revised]
PHST- 2021/09/16 00:00 [accepted]
PHST- 2021/09/28 01:19 [entrez]
PHST- 2021/09/29 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2021/09/20 00:00 [pmc-release]
AID - ijms221810140 [pii]
AID - ijms-22-10140 [pii]
AID - 10.3390/ijms221810140 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Sep 20;22(18):10140. doi: 10.3390/ijms221810140.