Advances in Fatty Acid Metabolism as the Markers of Civilization Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: closed (1 December 2022) | Viewed by 10428

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Guest Editor
Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 70-204 Szczecin, Poland
Interests: fatty acids metabolism; inflammatory process; eicosanoids; SCFA; PUFA; MUFA; nutriepigenomics; chromatography; ischemic stroke; NAFLD; NASH
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Special Issue Information

Dear Colleagues,

Fatty acids (FA), as the basic component of cell membranes, participate in maintaining the homeostasis of cellular metabolism, cell signaling and gene expression. Fatty acids are a biochemically diverse group of organic compounds in terms of their structure and origin. Regulatory functions in humans body are performed by both SCFA short-chain fatty acids, produced by the bacteria from gut microbiome, and dietary fatty acids, mainly PUFA n3 and n6. The FA are very important factors modifying a number of metabolic pathways in our body, and at the same time being their components. Eicosanoids, EPA and DHA derivatives, such as prostaglandins, leukotrienes, resolvins, protectins and maresins, are anti-inflammatory or pro-inflammatory mediators. Low-intensity inflammation may be associated with susceptibility to developing non-communicable chronic diseases (NCCD), such as obesity, lipid disorders and NAFLD, cardiovascular diseases (CVD), type 2 diabetes (T2D), insulin resistance , or some types of cancers. It is also believed that disturbance of lipid homeostasis is also associated with neurological disorders as well as neurodegenerative diseases such as Alzheimer's disease (AD).

I have hope that the recent advances in lipidometabolomics help a better understanding of the role of some nutritional factors, including fatty acids, in the development of civilization diseases. It is possible that understanding the fatty acid profile in these diseases will allow for the development of new diagnostic, therapeutic, and prophylactic strategies. I invite scientists to share their experiences in this area in the form of original research and review articles.

Dr. Arleta Drozd
Guest Editor

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Keywords

  • fatty acids
  • lipidomics
  • biochemistry
  • infalmmation
  • pathophysiological mechanisms
  • lipid mediators
  • gut microbiota
  • NAFLD/NASH
  • insulin resistance
  • type 2 diabetes
  • endocine diseases
  • cardiovascular diseases

Published Papers (6 papers)

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Research

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19 pages, 2086 KiB  
Article
Smoking Affects the Post-Stroke Inflammatory Response of Lipid Mediators in a Gender-Related Manner
by Arleta Drozd, Dariusz Kotlęga, Krzysztof Dmytrów and Małgorzata Szczuko
Biomedicines 2023, 11(1), 92; https://doi.org/10.3390/biomedicines11010092 - 29 Dec 2022
Viewed by 1435
Abstract
The main goal of our study was to determine the effect of cigarette smoking on selected derivatives of arachidonic acid, linoleic acid, DHA, and EPA, which may be markers of post-stroke inflammation. The eicosanoid profile was compared in both smoking and non-smoking patients, [...] Read more.
The main goal of our study was to determine the effect of cigarette smoking on selected derivatives of arachidonic acid, linoleic acid, DHA, and EPA, which may be markers of post-stroke inflammation. The eicosanoid profile was compared in both smoking and non-smoking patients, without division and with division into gender. In the group of non-smokers, we observed higher levels of the linolenic acid derivative (LA) 9S HODE (p ≤ 0.05) than in smokers. However, after dividing the results by sex, it turned out that the level of this derivative was higher in non-smoking women compared to smoking women (p ≤ 0.01) and did not differentiate the group of men. Similarly, the level of the arachidonic acid metabolite LTX A4 (p ≤ 0.05) differed only in the group of women. In this group, we also observed a decreased level of 15S HETE in smoking women, but it was statistically insignificant (p ≤ 0.08). On the other hand, the level of this derivative was statistically significantly higher in the group of non-smoking women compared to male non-smokers. The group of men was differentiated by two compounds: TXB2 and NPD1. Male smokers had an almost two-fold elevation of TXB2 (p ≤ 0.01) compared with non-smokers, and in this group, we also observed an increased level of NPD1 compared with male non-smokers. On the other hand, when comparing female non-smokers and male non-smokers, in addition to the difference in 15S HETE levels, we also observed elevated levels of TXB2 in the group of non-smokers. We also analyzed a number of statistically significant correlations between the analyzed groups. Generally, men and women smokers showed a much smaller amount of statistically significant correlations than non-smokers. We believe that this is related to the varying degrees of inflammation associated with acute ischemic stroke and post-stroke response. On the one hand, tobacco smoke inhibits the activity of enzymes responsible for the conversion of fatty acids, but on the other hand, it can cause the failure of the inflammatory system, which is also the body’s defense mechanism. Smoking cigarettes is a factor that increases oxidative stress even before the occurrence of a stroke incident, and at the same time accelerates it and inhibits post-stroke repair mechanisms. This study highlights the effect of smoking on inflammation in both genders mediated by lipid mediators, which makes smoking cessation undeniable. Full article
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15 pages, 2422 KiB  
Article
Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet
by Huawei Zeng, Bryan D. Safratowich, Wen-Hsing Cheng, Andrew D. Magnuson and Matthew J. Picklo
Biomedicines 2022, 10(11), 2891; https://doi.org/10.3390/biomedicines10112891 - 11 Nov 2022
Viewed by 1279
Abstract
High-fat diet (HFD)-induced obesity is a risk factor for colon cancer. Our previous data show that compared to an AIN-93 diet (AIN), a HFD promotes azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation and microbial dysbiosis in C57BL/6 mice. To explore the underlying [...] Read more.
High-fat diet (HFD)-induced obesity is a risk factor for colon cancer. Our previous data show that compared to an AIN-93 diet (AIN), a HFD promotes azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation and microbial dysbiosis in C57BL/6 mice. To explore the underlying metabolic basis, we hypothesize that AOM treatment triggers a different fecal metabolomic profile in C57BL/6 mice fed the HFD or the AIN. We found that 65 of 196 identified metabolites were significantly different among the four groups of mice (AIN, AIN + AOM, HFD, and HFD + AOM). A sparse partial least squares discriminant analysis (sPLSDA) showed that concentrations of nine fecal lipid metabolites were increased in the HFD + AOM compared to the HFD, which played a key role in overall metabolome group separation. These nine fecal lipid metabolite concentrations were positively associated with the number of colonic ACF, the cell proliferation of Ki67 proteins, and the abundance of dysbiotic bacteria. These data suggest that the process of AOM-induced ACF formation may increase selective fecal lipid concentrations in mice fed with a HFD but not an AIN. Collectively, the accumulation of these critical fecal lipid species may alter the overall metabolome during tumorigenesis in the colon. Full article
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15 pages, 1005 KiB  
Article
Plasma Fatty Acid Composition Is Associated with Histological Findings of Nonalcoholic Steatohepatitis
by Teruki Miyake, Shinya Furukawa, Bunzo Matsuura, Osamu Yoshida, Masumi Miyazaki, Akihito Shiomi, Sayaka Kanzaki, Hironobu Nakaguchi, Kotaro Sunago, Yoshiko Nakamura, Yusuke Imai, Takao Watanabe, Yasunori Yamamoto, Yohei Koizumi, Yoshio Tokumoto, Masashi Hirooka, Teru Kumagi, Masanori Abe and Yoichi Hiasa
Biomedicines 2022, 10(10), 2540; https://doi.org/10.3390/biomedicines10102540 - 12 Oct 2022
Cited by 4 | Viewed by 1432
Abstract
The relationship between advanced nonalcoholic steatohepatitis (NASH) and plasma fatty acid composition remains unknown. We aimed to examine the plasma fatty acid composition in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) and evaluate the relationship between histological findings and fatty acid composition. Overall, 235 [...] Read more.
The relationship between advanced nonalcoholic steatohepatitis (NASH) and plasma fatty acid composition remains unknown. We aimed to examine the plasma fatty acid composition in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) and evaluate the relationship between histological findings and fatty acid composition. Overall, 235 patients (134 women) with NAFLD were enrolled. Comprehensive blood chemistry tests and histological examinations of liver samples were conducted. Multivariate analyses adjusted for age, sex, body mass index, alanine aminotransferase, hemoglobin A1c, creatinine, total cholesterol, triglyceride, and NAFLD Activity Score values showed that lower levels of arachidic, behenic, α-linolenic, eicosatetraenoic, docosapentaenoic, and docosahexaenoic acids and higher levels of mead acid were associated with fibrosis stage 3–4. Furthermore, higher lauric acid, myristic acid, and palmitic acid levels and monounsaturated fatty acids such as palmitoleic acid and oleic acid were significantly associated with high NAS in analyses adjusted for the same factors and fibrosis stage. The plasma fatty acid composition was associated with the histological evidence of NASH. Increased synthesis of fatty acids is associated with NASH; insufficient intake of n-3 essential fatty acids and reduced elongation of fatty acids are associated with fibrosis in NASH. These features may help clinicians to understand and treat advanced NASH cases. Full article
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16 pages, 2353 KiB  
Article
Saturated Fatty Acid Blood Levels and Cardiometabolic Phenotype in Patients with HFpEF: A Secondary Analysis of the Aldo-DHF Trial
by Katharina Lechner, Clemens von Schacky, Johannes Scherr, Elke Lorenz, Matthias Bock, Benjamin Lechner, Bernhard Haller, Alexander Krannich, Martin Halle, Rolf Wachter, André Duvinage and Frank Edelmann
Biomedicines 2022, 10(9), 2296; https://doi.org/10.3390/biomedicines10092296 - 15 Sep 2022
Cited by 5 | Viewed by 1621
Abstract
Background: Circulating long-chain (LCSFAs) and very long-chain saturated fatty acids (VLSFAs) have been differentially linked to risk of incident heart failure (HF). In patients with heart failure with preserved ejection fraction (HFpEF), associations of blood SFA levels with patient characteristics are unknown. Methods: [...] Read more.
Background: Circulating long-chain (LCSFAs) and very long-chain saturated fatty acids (VLSFAs) have been differentially linked to risk of incident heart failure (HF). In patients with heart failure with preserved ejection fraction (HFpEF), associations of blood SFA levels with patient characteristics are unknown. Methods: From the Aldo-DHF-RCT, whole blood SFAs were analyzed at baseline in n = 404 using the HS-Omega-3-Index® methodology. Patient characteristics were 67 ± 8 years, 53% female, NYHA II/III (87%/13%), ejection fraction ≥50%, E/e’ 7.1 ± 1.5; and median NT-proBNP 158 ng/L (IQR 82–298). Spearman´s correlation coefficients and linear regression analyses, using sex and age as covariates, were used to describe associations of blood SFAs with metabolic phenotype, functional capacity, cardiac function, and neurohumoral activation at baseline and after 12-month follow-up (12 mFU). Results: In line with prior data supporting a potential role of de novo lipogenesis-related LCSFAs in the development of HF, we showed that baseline blood levels of C14:0 and C16:0 were associated with cardiovascular risk factors and/or lower exercise capacity in patients with HFpEF at baseline/12 mFU. Contrarily, the three major circulating VLSFAs, lignoceric acid (C24:0), behenic acid (C22:0), and arachidic acid (C20:0), as well as the LCSFA C18:0, were broadly associated with a lower risk phenotype, particularly a lower risk lipid profile. No associations were found between cardiac function and blood SFAs. Conclusions: Blood SFAs were differentially linked to biomarkers and anthropometric markers indicative of a higher-/lower-risk cardiometabolic phenotype in HFpEF patients. Blood SFA warrant further investigation as prognostic markers in HFpEF. One Sentence Summary: In patients with HFpEF, individual circulating blood SFAs were differentially associated with cardiometabolic phenotype and aerobic capacity. Full article
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14 pages, 2111 KiB  
Article
Effect of Lauric vs. Oleic Acid-Enriched Diets on Leptin Autoparacrine Signalling in Male Mice
by Jesús Fernández-Felipe, Adrián Plaza, Gema Domínguez, Javier Pérez-Castells, Victoria Cano, Francesco Cioni, Nuria Del Olmo, Mariano Ruiz-Gayo and Beatriz Merino
Biomedicines 2022, 10(8), 1864; https://doi.org/10.3390/biomedicines10081864 - 02 Aug 2022
Cited by 2 | Viewed by 1420
Abstract
High-fat diets enriched with lauric acid (SOLF) do not enhance leptin production despite expanding white adipose tissue (WAT). Our study aimed at identifying the influence of SOLF vs. oleic acid-enriched diets (UOLF) on the autoparacrine effect of leptin and was carried out on [...] Read more.
High-fat diets enriched with lauric acid (SOLF) do not enhance leptin production despite expanding white adipose tissue (WAT). Our study aimed at identifying the influence of SOLF vs. oleic acid-enriched diets (UOLF) on the autoparacrine effect of leptin and was carried out on eight-week-old mice consuming control chow, UOLF or SOLF. Phosphorylation of kinases integral to leptin receptor (LepR) signalling pathways (705Tyr-STAT3, 473Ser-Akt, 172Thr-AMPK), adipocyte-size distribution, fatty acid content, and gene expression were analyzed in WAT. SOLF enhanced basal levels of phosphorylated proteins but reduced the ability of leptin to enhance kinase phosphorylation. In contrast, UOLF failed to increase basal levels of phosphorylated proteins and did not modify the effect of leptin. Both SOLF and UOLF similarly affected adipocyte-size distribution, and the expression of genes related with adipogenesis and inflammation. WAT composition was different between groups, with SOLF samples mostly containing palmitic, myristic and lauric acids (>48% w/w) and UOLF WAT containing more than 80% (w/w) of oleic acid. In conclusion, SOLF appears to be more detrimental than UOLF to the autoparacrine leptin actions, which may have an impact on WAT inflammation. The effect of SOLF and UOLF on WAT composition may affect WAT biophysical properties, which are able to condition LepR signaling. Full article
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Review

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21 pages, 6560 KiB  
Review
The Modulatory Effects of Fatty Acids on Cancer Progression
by Annemarie J. F. Westheim, Lara M. Stoffels, Ludwig J. Dubois, Jeroen van Bergenhenegouwen, Ardy van Helvoort, Ramon C. J. Langen, Ronit Shiri-Sverdlov and Jan Theys
Biomedicines 2023, 11(2), 280; https://doi.org/10.3390/biomedicines11020280 - 19 Jan 2023
Cited by 2 | Viewed by 2424
Abstract
Cancer is the second leading cause of death worldwide and the global cancer burden rises rapidly. The risk factors for cancer development can often be attributed to lifestyle factors, of which an unhealthy diet is a major contributor. Dietary fat is an important [...] Read more.
Cancer is the second leading cause of death worldwide and the global cancer burden rises rapidly. The risk factors for cancer development can often be attributed to lifestyle factors, of which an unhealthy diet is a major contributor. Dietary fat is an important macronutrient and therefore a crucial part of a well-balanced and healthy diet, but it is still unclear which specific fatty acids contribute to a healthy and well-balanced diet in the context of cancer risk and prognosis. In this review, we describe epidemiological evidence on the associations between the intake of different classes of fatty acids and the risk of developing cancer, and we provide preclinical evidence on how specific fatty acids can act on tumor cells, thereby modulating tumor progression and metastasis. Moreover, the pro- and anti-inflammatory effects of each of the different groups of fatty acids will be discussed specifically in the context of inflammation-induced cancer progression and we will highlight challenges as well as opportunities for successful application of fatty acid tailored nutritional interventions in the clinic. Full article
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