Lipid-derived mediators play crucial roles in inflammation and immune responses. They are bioactive molecules produced from polyunsaturated fatty acids PUFAs and other lipids, which can modulate cellular functions and signaling pathways. Some of the most well-known lipid-derived mediators include prostaglandins, leukotrienes, and specialized pro-resolving mediators SPMs such as resolvins, protectins, and maresins.Roles and mechanisms of lipid-derived mediators in inflammation and immune responses:1. Prostaglandins: These are produced from arachidonic acid through the action of cyclooxygenase COX enzymes. Prostaglandins have diverse roles in inflammation, including vasodilation, increased vascular permeability, and modulation of immune cell functions. For example, prostaglandin E2 PGE2 can promote the production of pro-inflammatory cytokines and enhance the activity of immune cells like macrophages and T cells.2. Leukotrienes: Derived from arachidonic acid via the 5-lipoxygenase 5-LOX pathway, leukotrienes are potent mediators of inflammation. They can induce bronchoconstriction, increase vascular permeability, and recruit immune cells to the site of inflammation. Leukotriene B4 LTB4 is a potent chemoattractant for neutrophils and plays a significant role in the initiation of the inflammatory response.3. Specialized pro-resolving mediators SPMs : SPMs, including resolvins, protectins, and maresins, are derived from omega-3 PUFAs like eicosapentaenoic acid EPA and docosahexaenoic acid DHA . They play essential roles in resolving inflammation and promoting tissue repair. SPMs can inhibit the production of pro-inflammatory mediators, reduce immune cell infiltration, and enhance phagocytosis of apoptotic cells and cellular debris by macrophages.Alterations in lipid metabolism and the pathogenesis of metabolic diseases:Dysregulation of lipid metabolism can contribute to the development of metabolic diseases such as obesity and type 2 diabetes. Some ways in which altered lipid metabolism contributes to these diseases include:1. Ectopic lipid accumulation: Excess lipid accumulation in non-adipose tissues, such as the liver, skeletal muscle, and pancreas, can lead to lipotoxicity, cellular dysfunction, and insulin resistance, which are hallmarks of type 2 diabetes.2. Altered adipokine secretion: Adipose tissue secretes various bioactive molecules called adipokines, which can modulate inflammation, insulin sensitivity, and energy metabolism. Dysregulated adipokine secretion in obesity, such as increased production of pro-inflammatory cytokines and reduced secretion of adiponectin, can promote insulin resistance and inflammation.3. Imbalance in pro-inflammatory and pro-resolving lipid mediators: Obesity and type 2 diabetes are associated with an imbalance in the production of pro-inflammatory lipid mediators e.g., prostaglandins and leukotrienes and pro-resolving lipid mediators e.g., SPMs . This imbalance can lead to chronic low-grade inflammation, which contributes to insulin resistance and the progression of metabolic diseases.4. Altered fatty acid composition: High intake of saturated and trans fats, along with reduced consumption of omega-3 PUFAs, can contribute to the development of obesity and type 2 diabetes. These dietary patterns can promote inflammation, impair insulin signaling, and alter the production of lipid-derived mediators.In conclusion, lipid-derived mediators play essential roles in inflammation and immune responses, and alterations in lipid metabolism can contribute to the pathogenesis of metabolic diseases such as obesity and type 2 diabetes. Understanding the mechanisms by which lipid mediators modulate inflammation and metabolic processes may provide novel therapeutic targets for the treatment of these diseases.