Oxylipins constitute a family of oxygenated
natural products which are formed from
fatty acids by pathways involving at least one step of
dioxygen-dependent
oxidation.[1] These small polar lipid compounds are metabolites of
polyunsaturated fatty acids (PUFAs) including omega-3 fatty acids and omega-6 fatty acids. [2][3] Oxylipins are formed by enyzmatic or non-enzymatic oxidation of PUFAs. [2]
In animal species, four main pathways of oxylipin production prevail:
lipoxygenases (LOXs) pathway, cyklooxygenases (COXs) route,
cytochrome P450 (CYPs) pathway, and
reactive oxygen species (ROS) route. [4] These pathways result in formation of many different oxylipin molecules which are important for number of processes in living organisms. The processes include inflamation, blood flow, energy metabolism, cellular life, cell signaling, or muscle contractions. [2][3][4] Oxylipins have both pro- and anti-inflamatory roles. [5]
Most oxylipins in the body are derived from
linoleic acid or
alpha-linolenic acid. Linoleic acid oxylipins are usually present in blood and tissue in higher concentrations than any other
PUFA oxylipin, despite the fact that alpha-linolenic acid is more readily metabolized to oxylipin.[9]
Linoleic acid oxylipins can be anti-inflammatory, but are more often pro-inflammatory, associated with
atherosclerosis,
non-alcoholic fatty liver disease, and
Alzheimer's disease.[9] Centenarians have shown reduced levels of linoleic acid oxylipins in their blood circulation.[10] Lowering dietary linoleic acid results in fewer linoleic acid oxylipins in humans.[11] From 1955 to 2005 the linoleic acid content of human
adipose tissue has risen an estimated 136% in the United States.[12]
In general, oxylipins derived from
omega-6 fatty acids are more pro-inflammatory, vasoconstrictive, and proliferative than those derived from
omega-3 fatty acids.[9] The omega-3
eicosapentaenoic acid (EPA)-derived and
docosahexaenoic acid (DHA)-derived oxylipins are anti-inflammatory and vasodilatory.[9] In a clinical trial of men with high
triglycerides, 3 grams daily of DHA compared with placebo (olive oil) given for 91 days nearly tripled the DHA in red blood cells while reducing oxylipins in those cells.[13] Both groups were given Vitamin C (
ascorbyl palmitate) and Vitamin E (mixed
tocopherol) supplements.[13]
Oxylipins and disease
Oxylipins play important role in many diseases, for example,
diabetes,
obesity,
cardiovascular diseases,
cancer,
COVID-19, or
neurodegenerative disorders. Changes in oxylipin metabolism have been reported in these diseases. [3][4][14][15][16][17] In 2021,
Alzheimer's disease was associated with changes in oxylipin levels in plasma and cerebrospinal fluid (CSF) for the first time. [18] Interestingly, improvement in neurodegenerative diseases and also cardiovascular diseases may be achieved by using inhibitors of an enzyme (soluble epoxide hydrolase) involved in formation of oxylipins. [19][20] In
Parkinson's disease, oxylipin profiles reflect the stage of the disease. This should be taken into consideration when choosing the suitable medication for Parkinson's disease. [15]
^Wolfer AM, Gaudin M, Taylor-Robinson SD, Holmes E, Nicholson JK (December 2015). "Development and Validation of a High-Throughput Ultrahigh-Performance Liquid Chromatography-Mass Spectrometry Approach for Screening of Oxylipins and Their Precursors". Analytical Chemistry. 87 (23): 11721–11731.
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10.1021/acs.analchem.5b02794.
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^Zhao J, Davis LC, Verpoorte R (June 2005). "Elicitor signal transduction leading to production of plant secondary metabolites". Biotechnology Advances. 23 (4): 283–333.
doi:
10.1016/j.biotechadv.2005.01.003.
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^Bolwell GP, Bindschedler LV, Blee KA, Butt VS, Davies DR, Gardner SL, et al. (May 2002). "The apoplastic oxidative burst in response to biotic stress in plants: a three-component system". Journal of Experimental Botany. 53 (372): 1367–1376.
doi:
10.1093/jexbot/53.372.1367.
PMID11997382.
^Biagini D, Oliveri P, Baj A, Gasperina DD, Ferrante FD, Lomonaco T, et al. (December 2023). "The effect of SARS-CoV-2 variants on the plasma oxylipins and PUFAs of COVID-19 patients". Prostaglandins & Other Lipid Mediators. 169: 106770.
doi:
10.1016/j.prostaglandins.2023.106770.
PMID37633481.
^Chaves-Filho AB, Diniz LS, Santos RS, Lima RS, Oreliana H, Pinto IF, et al. (November 2023). "Plasma oxylipin profiling by high resolution mass spectrometry reveal signatures of inflammation and hypermetabolism in amyotrophic lateral sclerosis". Free Radical Biology & Medicine. 208: 285–298.
doi:
10.1016/j.freeradbiomed.2023.08.019.
PMID37619957.
^Tans R, Bande R, van Rooij A, Molloy BJ, Stienstra R, Tack CJ, et al. (September 2020). "Evaluation of cyclooxygenase oxylipins as potential biomarker for obesity-associated adipose tissue inflammation and type 2 diabetes using targeted multiple reaction monitoring mass spectrometry". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 160: 102157.
doi:
10.1016/j.plefa.2020.102157.
hdl:2066/222812.
PMID32629236.