Role of Oxylipins in the Inflammatory-Related Diseases NAFLD, Obesity, and Type 2 Diabetes

Abstract

Oxygenated polyunsaturated fatty acids (oxylipins) are bioactive molecules established as important mediators during inflammation. Different classes of oxylipins have been found to have opposite effects, e.g., pro-inflammatory prostaglandins and anti-inflammatory resolvins. Production of the different classes of oxylipins occurs during distinct stages of development and resolution of inflammation. Chronic inflammation is involved in the progression of many pathophysiological conditions and diseases such as non-alcoholic fatty liver disease, insulin resistance, diabetes, and obesity. Determining oxylipin profiles before, during, and after inflammatory-related diseases could provide clues to the onset, development, and prevention of detrimental conditions. This review focusses on recent developments in our understanding of the role of oxylipins in inflammatory disease, and outlines novel technological advancements and approaches to study their action.

Keywords: diagnosis; eicosanoid; inflammation; mass spectrometry; progression; treatment.

Figure 1

General overview of essential and non-essential polyunsaturated fatty acids. LA is a non-essential fatty acid and precursor of the omega-6 series of fatty acids and eicosanoids which have mostly pro-inflammatory action. ALA is a non-essential fatty acid and precursor of the omega-3 series of fatty acids and eicosanoids which have predominantly anti-inflammatory effect. Omega-6 and omega-3 double bonds are marked in red. Chemical formulas were created using ChemDraw^®. More detailed description of the role of PUFAs in inflammatory processes, including exceptions, is outlined in the main text.

Figure 2

Arachidonic acid is the main precursor of eicosanoids. Eicosanoids can be produced enzymatically by COX, LOX, and CYP, and non-enzymatically. COX-derived eicosanoids include prostaglandins as well as 11-hydroxyeicosatetraenoic acid (HETE). CYP enzymatic activity produces EETs that are further hydrolysed to DHET by soluble epoxide hydrolase (sEH). HETEs, leukotrienes, hepoxilins, and lipoxins are produced by LOX. Leukotriene A4 is subjected to further non-enzymatic hydrolysis to form Leukotriene B4 LTB4 and its derivatives. Non-enzymatic oxidation of AA results in the formation of eicosanoids used as markers of oxidative stress in vivo. Chemical formula for AA was created using ChemDraw^®.