title: Hydroxyoctadecadienoic acids: Oxidised derivatives of linoleic acid and their role in inflammation associated with metabolic syndrome and cancer.
abstract: Linoleic acid (LA) is a major constituent of low-density lipoproteins. An essential fatty acid, LA is a polyunsaturated fatty acid, which is oxidised by endogenous enzymes and reactive oxygen species in the circulation. Increased levels of low-density lipoproteins coupled with oxidative stress and lack of antioxidants drive the oxidative processes. This results in synthesis of a range of oxidised derivatives, which play a vital role in regulation of inflammatory processes. The derivatives of LA include, hydroxyoctadecadienoic acids, oxo-​octadecadienoic acids, epoxy octadecadecenoic acid and epoxy-keto-octadecenoic acids. In this review, we examine the role of LA derivatives and their actions on regulation of inflammation relevant to metabolic processes associated with atherogenesis and cancer. The processes affected by LA derivatives include, alteration of airway smooth muscles and vascular wall, affecting sensitivity to pain, and regulating endogenous steroid hormones associated with metabolic syndrome. LA derivatives alter cell adhesion molecules, this initial step, is pivotal in regulating inflammatory processes involving transcription factor peroxisome proliferator-activated receptor pathways, thus, leading to alteration of metabolic processes. The derivatives are known to elicit pleiotropic effects that are either beneficial or detrimental in nature hence making it difficult to determine the exact role of these derivatives in the progress of an assumed target disorder. The key may lie in understanding the role of these derivatives at various stages of development of a disorder. Novel pharmacological approaches in altering the synthesis or introduction of synthesised LA derivatives could possibly help drive processes that could regulate inflammation in a beneficial manner. Chemical Compounds: Linoleic acid (PubChem CID: 5280450), 9- hydroxyoctadecadienoic acid (PubChem CID: 5312830), 13- hydroxyoctadecadienoic acid (PubChem CID: 6443013), 9-oxo-​octadecadienoic acid (PubChem CID: 3083831), 13-oxo-​octadecadienoic acid (PubChem CID: 4163990), 9,10-epoxy-12-octadecenoate (PubChem CID: 5283018), 12,13-epoxy-9-keto-10- trans -octadecenoic acid (PubChem CID: 53394018), Pioglitazone (PubChem CID: 4829).
authors.affiliation: College of Medicine and Dentistry, James Cook University, Queensland 4811, Australia. Electronic address: venkat.vangaveti@jcu.edu.au.
authors.forename: Venkat N
authors.initials: VN
authors.lastname: Vangaveti
authors.affiliation: College of Medicine and Dentistry, James Cook University, Queensland 4811, Australia.
authors.forename: Holger
authors.initials: H
authors.lastname: Jansen
authors.affiliation: Faculty of Health, Deakin University, Waurn Ponds Campus, Geelong, VIC 3220, Australia.
authors.forename: Richard Lee
authors.initials: RL
authors.lastname: Kennedy
authors.affiliation: College of Medicine and Dentistry, James Cook University, Queensland 4811, Australia; Townsville Hospital, Department of Diabetes & Endocrinology, 100 Angus Smith Drive, Townsville, Queensland 4814, Australia.
authors.forename: Usman H
authors.initials: UH
authors.lastname: Malabu
mesh_terms: D000818:Animals; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D019787:Linoleic Acid / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction
chemical_list: D005231:Fatty Acids, Unsaturated; C495366:hydroxyoctadecadienoic acid; D019787:Linoleic Acid
keywords: Cancer; Hydroxyoctadecadienoic acids; Inflammation; Linoleic acid; Metabolic syndrome