Eicosanoids in Metabolic Syndrome

Abstract

Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that amplify the inflammatory response. In acute inflammation, the transcellular synthesis of antiinflammatory eicosanoids resolve inflammation, while persistent activation of the autacoid-cytokine-chemokine cascade in metabolic disease leads to chronic inflammation and accompanying tissue pathology. Many drugs targeting the eicosanoid pathways have been shown to be effective in the treatment of MetS, suggesting a common linkage between inflammation, MetS and drug metabolism.The cross-talk between inflammation and MetS seems apparent because of the growing evidence linking immune cell activation and metabolic disorders such as insulin resistance, dyslipidemia, and hypertriglyceridemia. Thus modulation of lipid metabolism through either dietary adjustment or selective drugs may become a new paradigm in the treatment of metabolic disorders. This review focuses on the mechanisms linking eicosanoid metabolism to persistent inflammation and altered lipid and carbohydrate metabolism in MetS.

Invited review: Inflammation during the transition to lactation: New adventures with an old flame

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Translational Implications of the Alcohol-Metabolizing Enzymes, Including Cytochrome P450-2E1, in Alcoholic and Nonalcoholic Liver Disease

“…Through uncoupling during its catalytic cycle, CYP4A-mediated metabolism can produce ROS . In addition, it can produce dicarboxylic acids of long-chain fatty acids, which can inhibit the mitochondrial ETC, increased oxidative stress, and toxicity (Hardwick, 2008;Hardwick et al, 2013).…”

Role of Cytochrome P450s in Inflammation

“…The links between eicosanoids and metabolic syndrome have been intensely investigated (Hardwick et al, 2013), and recently, there has been increased interest in the role of EETs. Obesity was significantly correlated with low plasma EET levels in a clinical study (Theken et al, 2012).…”