Immune regulation of poly unsaturated fatty acids and free fatty acid receptor 4

Duah, Maxwell; Zhang, Kexin; Liang, Yiwen; Ayarick, Vivian Adiila; Xu, Kailin; Pan, Bin

doi:10.1016/j.jnutbio.2022.109222

Cited by 11 publications

(10 citation statements)

References 138 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34 Cancer cells may potentially profit from FFAR4's influence on inflammation and energy balance, in addition to its immunosuppressive effect. 35 There were also some limitations of our study. Firstly, it would be more convincing to explore the accuracy of the prognostic signature in realistic esophageal cancer cohorts.…”

Section: Correlation Of Riskscore With Pathological Features and Time...mentioning

confidence: 88%

See 1 more Smart Citation

Dissecting the molecular profiling and tumor immune microenvironment of three subtypes of esophageal cancer

Zhang

et al. 2023

The Journal of Gene Medicine

View full text Add to dashboard Cite

Background: Great improvements have been made in the prognosis of esophageal cancer (ESCA) with the application of chemotherapy and immunotherapy. However, the majority of cases remain resistant to these regimens. Hence there is an urgent need to characterize the subtypes of ESCA with favorable survival outcome and drug responsiveness. Methods: We characterized the malignant cells of ESCA and explored their communication with immune cells using the Cellchat algorithm. The ligand-receptor interaction pairs were then used as inputting information to identify the subtypes of ESCA by unsupervised clustering analysis. Further investigation aimed to dissect the different patterns of tumor immune microenvironment (TIME), tumor mutation burden, immunotherapy responsiveness and drug sensitivity among the various subtypes of ESCA. A nomogram was also constructed to predict the survival rate of ESCA patients by conducting Cox regression and decision curve analysis.Results: Three subtypes were identified based on the ligand-receptor interaction pairs. Patients in cluster 2 showed a longer survival time and less likelihood of response to immunotherapy compared with cluster 1 or 3. Eight hub genes were screened to construct a prognostic signature, which can stratify patients well into high-and low-risk groups with distinct survival outcomes and drug sensitivities. The nomogram showed quite good performance in predicting patient survival rates of 1 and 3 years. Conclusion:This study characterized the molecular profiling and TIME patterns of three subtypes of ESCA. The relative findings will provide emergent insights for the treatment of ESCA.

show abstract

Section: Correlation Of Riskscore With Pathological Features and Time...mentioning

confidence: 88%

“…Free fatty acid receptor 4, also known as G protein‐coupled receptor 120, is extensively expressed in epithelial cells to control long‐chain fatty acid absorption 34 . Cancer cells may potentially profit from FFAR4's influence on inflammation and energy balance, in addition to its immunosuppressive effect 35 …”

Section: Discussionmentioning

confidence: 99%

Dissecting the molecular profiling and tumor immune microenvironment of three subtypes of esophageal cancer

Zhang

et al. 2023

The Journal of Gene Medicine

View full text Add to dashboard Cite

show abstract

“…Reducing the n -6/ n -3 PUFA ratio and increasing n -3 PUFA intake can significantly improve NAFLD [ 39 ]. Supplementation of n -3 PUFAs exerts a variety of health benefits on the human body by activating the FFAR4 signaling pathway [ 40 ]. In this study, our results showed that FFAR4 knockout blocked the protective effect of n -3 PUFAs on intestinal barrier function.…”

Section: Discussionmentioning

confidence: 99%

Endogenous n-3 PUFAs Improve Non-Alcoholic Fatty Liver Disease through FFAR4-Mediated Gut–Liver Crosstalk

Jiang

Yang

et al. 2023

Nutrients

View full text Add to dashboard Cite

The gut–liver axis plays a key role in the development and progression of non-alcoholic fatty liver disease (NAFLD). Due to the complexity and incomplete understanding of the cross-talk between the gut and liver, effective therapeutic targets are largely unknown. Free fatty acid receptors (FFARs) may bridge the cross-talk between the gut and liver. FFAR4 has received considerable attention due to its important role in lipid metabolism. However, the role of FFAR4 in this cross talk in NAFLD remains unclear. In this study, mice with high endogenous n-3 PUFAs but FFAR4 deficiency were generated by crossbreeding Fat-1 and FFAR4 knockout mice. FFAR4 deficiency blocked the protective effects of high endogenous n-3 PUFAs on intestinal barrier dysfunction and hepatic steatosis. In addition, FFAR4 deficiency decreased gut microbiota diversity and enriched Rikenella, Anaerotruncus, and Enterococcus, and reduced Dubosiella, Ruminococcaceae UCG-010, Ruminococcaceae UCG-014, Coriobacteriaceae UCG-002, Faecalibaculum, Ruminococcaceae UCG-009, and Akkermansia. Notably, FFAR4 deficiency co-regulated pantothenic acid and CoA biosynthesis, β-alanine metabolism, and sphingolipid metabolism pathways in the gut and liver, potentially associated with the aggravation of NAFLD. Together, the beneficial effects of n-3 PUFAs on the gut and liver were mediated by FFAR4, providing insights on the role of FFAR4 in the treatment of NAFLD through the gut–liver axis.

show abstract

“…AA and its metabolites have strong biological activity and can participate in the inflammatory response by activating various signaling pathways. Abnormal fatty acid metabolism can amplify the inflammatory response of infection by regulating the p38 MAPK signaling pathway 220,221 . Calcium signaling pathways in T cells promote synovial inflammation in patients with rheumatoid arthritis 222 .…”

Section: Aa Metabolism In Human Health and Diseasesmentioning

confidence: 99%

Arachidonic acid metabolism in health and disease

Zhang,

Liu,

Sun

et al. 2023

MedComm

View full text Add to dashboard Cite

Arachidonic acid (AA), an n‐6 essential fatty acid, is a major component of mammalian cells and can be released by phospholipase A2. Accumulating evidence indicates that AA plays essential biochemical roles, as it is the direct precursor of bioactive lipid metabolites of eicosanoids such as prostaglandins, leukotrienes, and epoxyeicosatrienoic acid obtained from three distinct enzymatic metabolic pathways: the cyclooxygenase pathway, lipoxygenase pathway, and cytochrome P450 pathway. AA metabolism is involved not only in cell differentiation, tissue development, and organ function but also in the progression of diseases, such as hepatic fibrosis, neurodegeneration, obesity, diabetes, and cancers. These eicosanoids are generally considered proinflammatory molecules, as they can trigger oxidative stress and stimulate the immune response. Therefore, interventions in AA metabolic pathways are effective ways to manage inflammatory‐related diseases in the clinic. Currently, inhibitors targeting enzymes related to AA metabolic pathways are an important area of drug discovery. Moreover, many advances have also been made in clinical studies of AA metabolic inhibitors in combination with chemotherapy and immunotherapy. Herein, we review the discovery of AA and focus on AA metabolism in relation to health and diseases. Furthermore, inhibitors targeting AA metabolism are summarized, and potential clinical applications are discussed.

show abstract

Immune regulation of poly unsaturated fatty acids and free fatty acid receptor 4

Cited by 11 publications

References 138 publications

Dissecting the molecular profiling and tumor immune microenvironment of three subtypes of esophageal cancer

Dissecting the molecular profiling and tumor immune microenvironment of three subtypes of esophageal cancer

Endogenous n-3 PUFAs Improve Non-Alcoholic Fatty Liver Disease through FFAR4-Mediated Gut–Liver Crosstalk

Arachidonic acid metabolism in health and disease

Contact Info

Product

Resources

About