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Fatty Acids as Modulators of Immune Function: Implications on Human...
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Fatty Acids as Modulators of Immune Function: Implications on Human Health

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutritional Immunology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 16922

Special Issue Editor

Dr. Megan L. Falsetta

E-Mail Website
Guest Editor
1. Department of Obstetrics and Gynecology, School of Medicine and Dentistry Rochester, University of Rochester, New York, NY, USA
2. Department of Pharmacology and Physiology, School of Medicine and Dentistry, University of Rochester, New York, NY, USA
Interests: translational women’s health research; to identify previously unknown mechanisms of disease for disabling vulvar conditions; namely vulvodynia and lichens; fatty acids

Special Issue Information

Dear Colleagues,

Omega-3 and omega-6 fatty acids are essential dietary polyunsaturated dietary fatty acids (PUFAs) that are metabolized to form lipids involved in both the propagation and resolution of inflammation. Therefore, they have important implications for immune function; deficits in the abundance or production of PUFA-derived bioactive lipids influence the pathophysiology of autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, type-1 diabetes, and systemic lupus erythematosus. Understanding the role of fatty acids in immune function and interventions targeted at preventing or correcting lipid dysbiosis represents a major step forward in treating immune disease.

In this topic, entitled “Fatty Acids as Modulators of Immune Function: Implications for Human Health,” we welcome submissions on fatty acid metabolism, lipid abundance and profiling, the connection between immune function and fatty acids or their respective lipids byproducts, and the role of dietary PUFAs in immune health.

Dr. Megan L. Falsetta
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • lipids
  • omega-3
  • omega-6
  • polyunsaturated fatty acids
  • specialized pro-resolving mediators
  • immune function
  • autoimmune disease

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Published Papers (5 papers)

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Research

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14 pages, 2779 KiB  
Article
Circulating Levels of Cathelicidin Antimicrobial Peptide (CAMP) Are Affected by Oral Lipid Ingestion
by Alexandra Höpfinger, Thomas Karrasch, Andreas Schäffler and Andreas Schmid
Nutrients 2023, 15(13), 3021; https://doi.org/10.3390/nu15133021 - 3 Jul 2023
Cited by 6 | Viewed by 1860
Abstract
Introduction: Obesity and related diseases are among the main public health issues in the western world. They are thought to be caused by a state of chronic, low-grade inflammation. Cathelicidin antimicrobial peptide (CAMP) was recently discovered to be expressed and secreted by adipocytes. [...] Read more.
Introduction: Obesity and related diseases are among the main public health issues in the western world. They are thought to be caused by a state of chronic, low-grade inflammation. Cathelicidin antimicrobial peptide (CAMP) was recently discovered to be expressed and secreted by adipocytes. Representing a novel immunomodulatory adipokine, CAMP might play an important role in the complex interaction between metabolism and inflammation. Methods: In a cohort of 80 volunteers, serum samples were collected prior to, and 2 h, 4 h, and 6 h after, oral lipid ingestion. CAMP, fatty acid binding proteins 2 and 4 (FABP-2/-4), and dipeptidylpeptidase-4 (DPP-4) serum concentrations were measured via ELISA. Human Simpson–Golabi–Behmel syndrome (SGBS) adipocytes were treated with free fatty acids, and gene expression levels of CAMP, FABP-4, and DPP-4 were quantified by RT-PCR. Results: The mean base-line CAMP serum concentration was 55.78 ± 29.26 ng/mL, with a range of 10.77–146.24 ng/mL. Interestingly, CAMP serum levels were positively correlated with LDL cholesterol, but negatively correlated with HDL cholesterol and adiponectin. Men exhibited higher CAMP serum concentrations than women, an effect apparently linked to oral contraception in the majority of female participants. In both genders, CAMP serum concentrations significantly decreased in a stepwise manner 4 h and 6 h after oral lipid ingestion. This decline was paralleled by a rise of serum bile acid and triglyceride levels upon lipid ingestion. In human SGBS adipocytes, treatment with free fatty acids did not affect CAMP gene expression, but increased FABP-4 gene expression. Conclusions: In conclusion, systemic levels of the antimicrobial peptide and novel adipokine CAMP are significantly decreased upon oral lipid ingestion. While this decline might be linked to the simultaneous increase in bile acids, the underlying mechanisms remain to be elucidated. Furthermore, CAMP might indicate a putative novel cardiovascular biomarker of both inflammatory and metabolic relevance in metaflammation and adipose inflammation. Full article
(This article belongs to the Special Issue Fatty Acids as Modulators of Immune Function: Implications on Human Health)
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14 pages, 6707 KiB  
Article
Docosahexaenoic Acid, a Key Compound for Enhancing Sensitization to Drug in Doxorubicin-Resistant MCF-7 Cell Line
by Sergio Crovella, Allal Ouhtit, Shaikh Mizanoor Rahman and Md Mizanur Rahman
Nutrients 2023, 15(7), 1658; https://doi.org/10.3390/nu15071658 - 29 Mar 2023
Cited by 8 | Viewed by 2758
Abstract
Drug resistance is a well-known and significant obstacle in the battle against cancer, rendering chemotherapy treatments often ineffective. To improve the effectiveness of chemotherapy, researchers are exploring the use of natural molecules that can enhance its ability to kill cancer cells and limit [...] Read more.
Drug resistance is a well-known and significant obstacle in the battle against cancer, rendering chemotherapy treatments often ineffective. To improve the effectiveness of chemotherapy, researchers are exploring the use of natural molecules that can enhance its ability to kill cancer cells and limit their spread. Docosahexaenoic acid (DHA), a lipid found in marine fish, has been shown to enhance the cytotoxicity of various anti-cancer drugs in vitro and in vivo. While the combined use of chemotherapeutic drugs with DHA demonstrated promising preliminary results in clinical trials, there is still a significant amount of information to be discovered regarding the precise mechanism of action of DHA. As the biological pathways involved in the chemosensitization of already chemoresistant MCF-7 cells are still not entirely unraveled, in this study, we aimed to investigate whether DHA co-treatment could enhance the ability of the chemotherapy drug doxorubicin to inhibit the growth and invasion of MCF-7 breast cancer cells (MCF-7/Dox) that had become resistant to the drug. Upon treating MCF-7/Dox cells with DHA or DHA–doxorubicin, it was observed that the DHA–doxorubicin combination effectively enhanced cancer cell death by impeding in vitro propagation and invasive ability. In addition, it led to an increase in doxorubicin accumulation and triggered apoptosis by arresting the cell cycle at the G2/M phase. Other observed effects included a decrease in the multi-drug resistance (MDR) carrier P-glycoprotein (P-gp) and TG2, a tumor survival factor. Augmented quantities of molecules promoting apoptosis such as Bak1 and caspase-3 and enhanced lipid peroxidation were also detected. Our findings in the cell model suggest that DHA can be further investigated as a natural compound to be used alongside doxorubicin in the treatment of breast cancer that is unresponsive to chemotherapy. Full article
(This article belongs to the Special Issue Fatty Acids as Modulators of Immune Function: Implications on Human Health)
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15 pages, 3241 KiB  
Article
CCN1/Integrin α5β1 Instigates Free Fatty Acid-Induced Hepatocyte Lipid Accumulation and Pyroptosis through NLRP3 Inflammasome Activation
by Qinyu Yao, Jia Liu, Qi Cui, Tingting Jiang, Xinya Xie, Xiong Du, Ziwei Zhao, Baochang Lai, Lei Xiao and Nanping Wang
Nutrients 2022, 14(18), 3871; https://doi.org/10.3390/nu14183871 - 19 Sep 2022
Cited by 9 | Viewed by 3031
Abstract
Hyperlipidemia with high blood levels of free fatty acids (FFA) is the leading cause of non-alcoholic steatohepatitis. CCN1 is a secreted matricellular protein that drives various cellular functions, including proliferation, migration, and differentiation. However, its role in mediating FFA-induced pro-inflammatory cell death and [...] Read more.
Hyperlipidemia with high blood levels of free fatty acids (FFA) is the leading cause of non-alcoholic steatohepatitis. CCN1 is a secreted matricellular protein that drives various cellular functions, including proliferation, migration, and differentiation. However, its role in mediating FFA-induced pro-inflammatory cell death and its underlying molecular mechanisms have not been characterized. In this study, we demonstrated that CCN1 was upregulated in the livers of obese mice. The increase in FFA-induced CCN1 was evaluated in vitro by treating hepatocytes with a combination of oleic acid and palmitic acid (2:1). Gene silencing using specific small interfering RNAs (siRNA) revealed that CCN1 participated in FFA-induced intracellular lipid accumulation, caspase-1 activation, and hepatocyte pyroptosis. Next, we identified integrin α5β1 as a potential receptor of CCN1. Co-immunoprecipitation demonstrated that the binding between CCN1 and integrin α5β1 increased in hepatocytes upon FFA stimulation in the livers of obese mice. Similarly, the protein levels of integrin α5 and β1 were increased in vitro and in vivo. Experiments with specific siRNAs confirmed that integrin α5β1 played a part in FFA-induced intracellular lipid accumulation, NLRP3 inflammasome activation, and pyroptosis in hepatocytes. In conclusion, these results provide novel evidence that the CCN1/integrin α5β1 is a novel mediator that drives hepatic lipotoxicity via NLRP3-dependent pyroptosis. Full article
(This article belongs to the Special Issue Fatty Acids as Modulators of Immune Function: Implications on Human Health)
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Review

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15 pages, 1566 KiB  
Review
Polyunsaturated Fatty Acids and Their Immunomodulatory Actions in Periodontal Disease
by Jeneen Panezai and Thomas van Dyke
Nutrients 2023, 15(4), 821; https://doi.org/10.3390/nu15040821 - 5 Feb 2023
Cited by 9 | Viewed by 3277
Abstract
Polyunsaturated fatty acids (PUFAs) are a diverse set of molecules with remarkable contributions to human physiology. They not only serve as sources of fuel but also cellular structural components as well as substrates that provide bioactive metabolites. A growing body of evidence demonstrates [...] Read more.
Polyunsaturated fatty acids (PUFAs) are a diverse set of molecules with remarkable contributions to human physiology. They not only serve as sources of fuel but also cellular structural components as well as substrates that provide bioactive metabolites. A growing body of evidence demonstrates their role in inflammation. Inflammation in the presence of a polymicrobial biofilm contributes to the pathology of periodontitis. The role PUFAs in modulating immuno-inflammatory reactions in periodontitis is only beginning to be uncovered as research continues to unravel their far-reaching immunologic implications. Full article
(This article belongs to the Special Issue Fatty Acids as Modulators of Immune Function: Implications on Human Health)
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13 pages, 1645 KiB  
Review
Significance of Gut Microbiota and Short-Chain Fatty Acids in Heart Failure
by Peng Zhao, Suhong Zhao, Jinwei Tian and Xinxin Liu
Nutrients 2022, 14(18), 3758; https://doi.org/10.3390/nu14183758 - 11 Sep 2022
Cited by 29 | Viewed by 5240
Abstract
Heart failure (HF), as the terminal stage of various heart diseases, seriously threatens an individual’s life, health, and quality of life. Emerging evidence has shown that the gut microbiota comprises an important component of human physiology and metabolic homeostasis, and can directly or [...] Read more.
Heart failure (HF), as the terminal stage of various heart diseases, seriously threatens an individual’s life, health, and quality of life. Emerging evidence has shown that the gut microbiota comprises an important component of human physiology and metabolic homeostasis, and can directly or indirectly affect the metabolic health of the host through metabolites. Upon in-depth study of intestinal microecology, the “gut-heart axis” appears to provide a novel direction for HF research. Thus, this review primarily focuses on the relationship between the gut microbiota and its major metabolites—i.e., short-chain fatty acids (SCFAs)—and HF. It explores the mechanisms underlying HF and its effective treatment by targeting SCFAs to optimize current HF treatment and thus improve the quality of patients’ lives. Full article
(This article belongs to the Special Issue Fatty Acids as Modulators of Immune Function: Implications on Human Health)
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