Table 1.
Role of some oxylipins in obesity.
| Role of AA–Derived Oxylipins | |
| PGD2 | PGD2 levels increase in mice fed a high-fat diet [92]. |
| PGE2 | PGE2 exhibits anti-lipolytic effects, leading to increased adipose tissue mass [91]. COX-2 and PGE2 levels increase in adipose tissue of obese patients [75,76]. |
| PGI2 | PGI2 increases adipogenesis via the PGI2 receptor [77]. Body weight gain is reduced in PGI synthase knockout mice feed a high-fat diet [77]. |
| 15d-PGJ2 | 15d-PGJ2 is a metabolite of PGD2 [8]. 15d-PGJ2 shows pro-adipogenic effect [93]. |
| 5-HETE | 5-LOX expression is upregulated in adipose tissue of obese patients [86]. The activity of 5-LOX is important in chronic and acute inflammation [94]. The inhibition of 5-LOX reduces hepatic macrophage infiltration in obese mice who have a high-fat diet [95]. An increase in 5-HETE promotes oxidative stress and increases reactive oxygen species, which may affect PUFA peroxidation [78]. |
| 11-HETE 15-HETE |
Increased 11- and 15-HETE concentrations are positively associated with BMI, waist circumference, and serum leptin levels [78]. |
| 12-HETE | 12-HETE induces inflammation and leukocyte infiltration in obese adipose tissue [89]. |
| LTB4 | LTB4 produced via the 5-LOX pathway is related to cytokine release [8]. LTB4 levels are increased in obese mice [79,80]. Inhibition of the LTB4 receptor improves the inflammatory profile by reducing peritoneal macrophage chemotaxis to target organs [79]. Excessive production of LTB4 triggers inflammation by causing increased chemotaxis of circulating B cells to WAT [96]. Leukocytes from obese people exhibit a four-fold increase in LTB4 [84]. |
| 20-HETE | 20-HETE contributes to rapid weight gain [90] |
| 14,15-EpETrE | EETs block the activation of NF-κB and reduce TNF-α [98]. Stimulation of adipogenesis in vitro and in vivo suppresses adipose-derived EET levels by dysregulating the CYP epoxygenase pathway [98]. Plasma levels of 14,15-EpETrE are positively correlated with adiposity [52]. 14,15-EpETrE levels are lower in fat-1 transgenic mice [57]. |
| Role of LA-derived oxylipins | |
| 9-HODE 13-HODE |
9-HODE and 13-HODE are associated with oxidative stress, inflammation, and numerous pathological and physiological conditions but the results are contradictory [8,78,92,94,102,103]. |
| 12,13-diHOME | 12,13-diHOME regulates metabolism and thermogenesis [104]. Plasma 12,13-diHOME concentration was associated with a lower BMI, visceral and total fat mass [19,81]. |
| Role of EPA-derived oxylipins | |
| 5-HEPE | 5-HEPE plays a role in body energy metabolism and browning of WAT [108]. 5-HEPE promotes BAT activation and browning of WAT by upregulating UCP-1 genes and protein expression [108]. |
| 12-HEPE | 12-HEPE is synthesized via the 12-LOX pathway [8]. 12-HEPE reduces the risk of obesity by regulating energy homeostasis and fuel utilization [72]. 12-HEPE levels are lower in obese people [72]. |
| Role of DHA-derived oxylipins | |
| 14-HDHA 17-HDHA |
14-HDHA and 17-HDHA are inflammation-resolving mediators [8]. 17-HDHA is reduced in WAT of obese mice [83]. 14-HDHA and 17-HDHA are lower in the plasma, serum, and leukocytes of obese than in healthy individuals [84]. |
| Rvs, PDs, MaRs | They actively resolve inflammation, protect organs, and stimulate tissue regeneration [8,67,84]. They decrease in response to obesity in various mouse tissues, including WAT, liver, bone marrow, and spleen [83,109]. Increasing the bioavailability of these mediators minimizes inflammation and mediates therapeutic effects [110]. |
11-HETE: 11-hydroxy-eicosatetraenoic acid, 12,13-DiHOME: 12,13-dihydroxy-9Z-octadecenoic acid, 12-HEPE: 12-hydroxy-eicosapentaenoic acid, 12-HETE: 12-hydroxy-eicosatetraenoic acid, 13-HODE: 13-hydroxy-octadecadienoic acid, 14,15-EpETrE: 14,15-epoxy-eicosatrienoic acid, 14-HDHA: 14-hydroxy-docosahexaenoic acid, 15d-PGJ2: 15-deoxy-Δ12,14-prostaglandin J2, 15-HETE: 15-hydroxy-eicosatetraenoic acid, 17-HDHA: 17-hydroxy-docosahexaenoic acid, 20-HETE: 20-hydroxy-eicosatetraenoic acid, 5-HEPE: 5-hydroxy-eicosapentaenoic acid, 5-HETE: 5-hydroxy-eicosatetraenoic acid, 9-HODE: 9-hydroxy-octadecadienoic acid, AA: Arachidonic acid, BAT: Brown adipose tissue, BMI: Body mass index, COX: Cyclooxygenase, CYP: Cytochrome P450, DHA: Docosapentaenoic acid, EET: Epoxyeicosatrienoic acids, EPA: Eicosapentaenoic acid, LA: Linoleic acid, LOX: Lipoxygenase, LTB4: Leukotriene B4, MaRs: Maresins, NF-κB: Nuclear factor kappa B, PDs: Protectins, PGD2: Prostaglandin D2, PGE2: Prostaglandin E2, PGI2: Prostaglandin I2, Rvs: Resolvins, TNF-α: Tumor necrosis factor alpha, WAT: White adipose tissue.