Arachidonic Acid as an Early Indicator of Inflammation during Non-Alcoholic Fatty Liver Disease Development

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excessive lipid deposition. Lipid metabolism disturbances are possibly associated with hepatocyte inflammation development and oxidative balance impairment. The aim of our experiment was to examine the first moment when changes in plasma and liver arachidonic acid (AA) levels as a pro-inflammatory precursor may occur during high-fat diet (HFD)-induced NAFLD development. Wistar rats were fed a diet rich in fat for five weeks, and after each week, inflammation and redox balance parameters were evaluated in the liver. The AA contents in lipid fractions were assessed by gas–liquid chromatography (GLC). Protein expression relevant to inflammatory and lipogenesis pathways was determined by immunoblotting. The oxidative system indicators were determined with assay kits. Our results revealed that a high-fat diet promoted an increase in AA levels, especially in the phospholipid (PL) fraction. Importantly, rapid inflammation development via increased inflammatory enzyme expression, elevated lipid peroxidation product content and oxidative system impairment was caused by the HFD as early as the first week of the experiment. Based on these results, we may postulate that changes in AA content may be an early indicator of inflammation and irreversible changes in NAFLD progression.

Untargeted and targeted metabolomics profiling reveals the underlying pathogenesis and abnormal arachidonic acid metabolism in laying hens with fatty liver hemorrhagic syndrome

“…Additionally, recent studies have indicated that a variety of biologically active metabolites produced by ARA also have a close relationship with oxidative stress, lipid metabolism, and immune function ( Hadley et al., 2016 ; Sonnweber et al., 2018 ). It has been demonstrated that ARA metabolism plays an important role in the occurring and development of NAFLD ( Arendt et al., 2015 ; Sztolsztener et al., 2020 ). For the similar pathogenesis of NAFLD and FLHS, it is interesting to explore the relationship of ARA metabolism and FLHS.…”

Metabolomics Analysis Coupled With UPLC/MS on Therapeutic Effect of Jigucao Capsule Against Dampness-Heat Jaundice Syndrome

“…The metabolites of arachidonic acid, as lipid mediators, play an important role in regulating the physiological function and pathology of the liver, such as prostaglandin E2, prostacyclin, thromboxane A2 and leukotriene C4. When liver injury occurs, macrophages gather in the liver and activate, resulting in the release of a large number of arachidonic acid metabolites, such as toxic prostaglandins, leukotrienes, TXs, free radicals and tumor necrosis factor-α, these toxic substances directly lead to the damage of hepatocytes (Chen et al, 2011;Sun et al, 2018a;Sztolsztener et al, 2020). Arachidonic acid, as an important inflammatory lipid mediator, regulates oxidative stress in hepatocyte mitochondria through three metabolic pathways of cyclooxygenase, lipoxygenase and cytochrome P450, resulting in the oxidation of a large number of fatty acids and the formation of lipid peroxides, the deposition of collagen in the liver, aggravating the injury of hepatocytes and the activation of hepatic stellate cells, and finally accelerating the injury of hepatocytes (Sacerdoti et al, 2003;Tallima, 2021).…”

The Beneficial Additive Effect of Silymarin in Metformin Therapy of Liver Steatosis in a Pre-Diabetic Model

“…After four weeks of MET and MET+SM treatment, AA profiles were reduced in the hepatic DAG lipid class. Changes in AA content are understood to be an early indicator of inflammation and NAFLD progression [54], and cytochrome P450 enzymes are supposed to be AA modulators [55]. CYP-AA metabolites HETEs and EETs have different properties and can be stored in tissue lipids.…”