ω-3 Polyunsaturated fatty acids-derived lipid metabolites on angiogenesis, inflammation and cancer

Wang, Weicang; Zhu, Julia; Lyu, Fei; Panigrahy, Dipak; Ferrara, Katherine W.; Hammock, Bruce D.; Zhang, Guodong

doi:10.1016/j.prostaglandins.2014.07.002

Cited by 122 publications

(113 citation statements)

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“…Apart from modulating the composition and function of cell membranes, V3FA can activate specific receptors (eg, GPR120 12 ) and are further metabolized into a series of bioactive lipids (eg, resolvins, protectins), which participate in cellular signaling and are intermingled with other lipid signaling systems, such as by acting as ligands of cannabinoidtype receptors. 27,28 This underlying complexity suggests that detailed action mechanisms of V3FA will vary to provide dynamic responses toward specific situations. More broadly, V3FA however do have phenotypic effects that may be considered as general attributes of these lipids.…”

Section: Discussionmentioning

confidence: 99%

Omega-3 Fatty Acids Protect Fatty and Lean Mouse Livers After Major Hepatectomy

et al. 2017

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Objective: The aim of this study was to assess the effect of V3 fatty acids (V3FA) on fatty and lean liver in hepatic surgery. Background: The global spread of energy-dense diets has led to an endemic rise in fatty liver disease and obesity. Besides metabolic pathologies, steatosis enhances hepatic sensitivity to ischemia reperfusion (I/R) and impedes liver regeneration (LR). Steatosis limits the application of liver surgery, still the main curative option for liver cancer. V3FA are known to reverse steatosis, but how these lipids affect key factors defining surgical outcomes-that is, I/R, LR, and liver malignancy-is less clear. Methods: We established a standardized mouse model of high fat diet (HFD)-induced steatosis followed by V3FA treatment and the subsequent assessment of V3FA effects on I/R, LR, and liver malignancy (n ¼ 5/group), the latter through a syngeneic metastasis approach. Fatty liver outcomes were compared with lean liver to assess steatosis-independent effects. Nonparametric statistics were applied. Results: V3FA reversed HFD-induced steatosis and markedly protected against I/R, improved LR, and prolonged survival of tumor-laden mice. Remarkably, these beneficial effects were also observed in lean liver, albeit at a smaller scale. Notably, mice with metastases in fatty versus lean livers were associated with improved survival. Conclusions: V3FA revealed multiple beneficial effects in fatty and lean livers in mice. The improvements in I/R injury, regenerative capacity, and oncological outcomes await confirmatory studies in humans.

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Section: Discussionmentioning

confidence: 99%

Omega-3 Fatty Acids Protect Fatty and Lean Mouse Livers After Major Hepatectomy

et al. 2017

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“…A general mechanism to explain the health benefits of ω-3 PUFAs is that they compete with arachidonic acid (ARA, 20:4ω-6) for the enzymatic metabolism by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes, leading to reduced formation of ω-6-series eicosanoids which are predominately pro-inflammatory and pro-tumorigenic, and increased formation of ω-3-series eicosanoid metabolites which are less-detrimental or even beneficial [10]. Recent research showed that ω-3 PUFAs, such as eicosapentaenoic acid (EPA, 20:5ω-3) and docosahexaenoic acid (DHA, 22:6ω-3), are highly efficient alternative substrates of CYP enzymes [11], while they are known as relatively poor substrates of COX and LOX enzymes [12].…”

Section: Introductionmentioning

confidence: 99%

ω-3 Polyunsaturated fatty acids and their cytochrome P450-derived metabolites suppress colorectal tumor development in mice

Wang

Yang

Nimiya

et al. 2017

The Journal of Nutritional Biochemistry

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Many studies have shown that dietary intake of ω-3 polyunsaturated fatty acids (PUFAs) reduces the risks of colorectal cancer, however the underlying mechanisms are not well understood. Here we used a LC-MS/MS-based lipidomics to explore the roles of eicosanoid signaling in the anti-colorectal cancer effects of ω-3 PUFAs. Our results showed that dietary feeding of ω-3 PUFAs-rich diets suppressed growth of MC38 colorectal tumor, and modulated profiles of fatty acids and eicosanoid metabolites in C57BL/6 mice. Notably, we found that dietary feeding of ω-3 PUFAs significantly increased levels of epoxydocosapentaenoic acids (EDPs, metabolites of ω-3 PUFA produced by cytochrome P450 enzymes) in plasma and tumor tissue of the treated mice. We further showed that systematic treatment with EDPs (dose = 0.5 mg/kg/day) suppressed MC38 tumor growth in mice, with reduced expressions of pro-oncogenic genes such as c-myc, Axin2, and C-jun in tumor tissues. Together, these results support that formation of EDPs might contribute to the anti-colorectal cancer effects of ω-3 PUFAs.

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“…Our finding suggested a protective role of DHA on cells exposed to PAHs. Differences in the membrane fatty acid profiles of cells may result from the use of FAs for biosynthesis of eicosanoids and from the differential expression of genes involved in the synthesis, elongation, and desaturation of FAs in the inflammatory state (Spite et al, 2014;Wang et al, 2014;Gdula-Argasinska et al, 2015).…”

Section: Discussionmentioning

confidence: 99%