scholarly journals Dietary omega-6, but not omega-3, polyunsaturated or saturated fatty acids increase inflammation in primary lung mesenchymal cells

2018 ◽  
Vol 314 (6) ◽  
pp. L922-L935 ◽  
Author(s):  
Sandra Rutting ◽  
Dia Xenaki ◽  
Edmund Lau ◽  
Jay Horvat ◽  
Lisa G. Wood ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Epithelial Cells ◽  
Airway Inflammation ◽  
Saturated Fatty Acids ◽  
Dietary Fatty Acids ◽  
Omega 3 ◽  
Obese Person ◽  
Tnf Α ◽  
Phosphoinositide 3 Kinase

Obesity is an important risk factor for developing severe asthma. Dietary fatty acids, which are increased in sera of obese individuals and after high-fat meals, activate the innate immune system and induce inflammation. This study investigated whether dietary fatty acids directly cause inflammation and/or synergize with obesity-induced cytokines in primary human pulmonary fibroblasts in vitro. Fibroblasts were challenged with BSA-conjugated fatty acids [ω-6 polyunsaturated fatty acids (PUFAs) and ω-3 PUFAs or saturated fatty acids (SFAs)], with or without TNF-α, and release of the proinflammatory cytokines, IL-6 and CXCL8, was measured. We found that the ω-6 PUFA arachidonic acid (AA), but not ω-3 PUFAs or SFAs, upregulates IL-6 and CXCL8 release. Combined AA and TNF-α challenge resulted in substantially greater cytokine release than either alone, demonstrating synergy. Synergistic upregulation of IL-6, but not CXCL8, was mainly mediated via cyclooxygenase (COX). Inhibition of p38 MAPK reduced CXCL8 release, induced by AA and TNF-α alone, but not in combination. Synergistic CXCL8 release, following AA and TNF-α challenge, was not medicated via a single signaling pathway (MEK1, JNK, phosphoinositide 3-kinase, and NF-κB) nor by hyperactivation of NF-κB or p38. To investigate if these findings occur in other airway cells, effects of AA in primary human airway smooth muscle (ASM) cells and human bronchial epithelial cells were also investigated. We found proinflammatory effects in ASM cells but not epithelial cells. This study suggests that diets rich in ω-6 PUFAs might promote airway inflammation via multiple pathways, including COX-dependent and -independent pathways, and in an obese person, may lead to more severe airway inflammation.

scholarly journals Omega-3 Fatty Acids and PPARγin Cancer

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-14 ◽  
Author(s):  
Iris J. Edwards ◽  
Joseph T. O'Flaherty
Keyword(s):  
Fatty Acids ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Dietary Fatty Acids ◽  
Human Populations ◽  
Peroxisome Proliferator ◽  
Omega 3 ◽  
New Paradigm

Omega-3 (or n-3) polyunsaturated fatty acids (PUFAs) and their metabolites are natural ligands for peroxisome proliferator receptor activator (PPAR)γand, due to the effects of PPARγon cell proliferation, survival, and differentiation, are potential anticancer agents. Dietary intake of omega-3 PUFAs has been associated with a reduced risk of certain cancers in human populations and in animal models. In vitro studies have shown that omega-3 PUFAs inhibit cell proliferation and induce apoptosis in cancer cells through various pathways but one of which involves PPARγactivation. The differential activation of PPARγand PPARγ-regulated genes by specific dietary fatty acids may be central to their distinct roles in cancer. This review summarizes studies relating PUFAs to PPARγand cancer and offers a new paradigm relating an n-3 PUFA through PPARγto the expression of the cell surface proteoglycan, syndecan-1, and to the death of cancer cells.

scholarly journals Bioaccessibility and Oxidative Stability of Omega-3 Fatty Acids in Supplements, Sardines and Enriched Eggs Studied Using a Static In Vitro Gastrointestinal Model

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 415
Author(s):  
Stylianos Floros ◽  
Alexandros Toskas ◽  
Evagelia Pasidi ◽  
Patroklos Vareltzis
Keyword(s):  
Fatty Acids ◽  
Bioactive Compounds ◽  
Dietary Habits ◽  
Healthy Lifestyle ◽  
Saturated Fatty Acids ◽  
Oxidation Products ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Simulated Digestion

Modern dietary habits have created the need for the design and production of functional foods enriched in bioactive compounds for a healthy lifestyle. However, the fate of many of these bioactive compounds in the human gastrointestinal (GI) tract has not been thoroughly investigated. Thus, in the present study, the bioaccessibility of omega-3 fatty acids was examined. To that end, different foods and supplements underwent simulated digestion following the INFOGEST protocol. The selected samples were foods rich in omega-3 fatty acids both in free and bound form—i.e., dietary fish oil supplements, heat-treated fish, and eggs enriched with omega-3 fatty acids. The oxidation of polyunsaturated fatty acids (PUFAs) was measured at each stage of the digestion process using peroxide value (PV) and TBARS and by quantifying individual omega-3 fatty acids using a gas chromatograph with flame ionization detector (GC-FID). The final bioaccessibility values of omega-3 fatty acids were determined. Changes in the quantity of mono-saturated fatty acids (MUFAs) and saturated fatty acids (SFAs) were recorded as well. The results indicated a profound oxidation of omega-3 fatty acids, giving rise to both primary and secondary oxidation products. Additionally, stomach conditions seemed to exert the most significant effect on the oxidation of PUFAs during digestion, significantly decreasing their bioaccessibility. The oxidation rate of each fatty acid was found to be strongly correlated with its initial concentration. Finally, the oxidation pattern was found to be different for each matrix and emulsified lipids seemed to be better protected than non-emulsified lipids. It is concluded that digestion has a profound negative effect on omega-3 bioaccessibility and therefore there is a need for improved protective mechanisms.

scholarly journals Dietary and Pharmacological Fatty Acids and Cardiovascular Health

2019 ◽  
Vol 105 (4) ◽  
pp. 1030-1045 ◽  
Author(s):  
Huaizhu Wu ◽  
Lu Xu ◽  
Christie M Ballantyne
Keyword(s):  
Fatty Acids ◽  
Clinical Trials ◽  
Polyunsaturated Fatty Acids ◽  
Cardiovascular Health ◽  
Evidence Synthesis ◽  
Saturated Fatty Acids ◽  
Saturated Fat ◽  
Dietary Fatty Acids ◽  
Atherosclerotic Cardiovascular Disease ◽  
Omega 3

Abstract Context The effects of dietary intake of different fatty acids and pharmacological use of fatty acids, specifically long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), on cardiovascular health and atherosclerotic cardiovascular disease (ASCVD) prevention have been examined in a large number of observational studies and clinical trials. This review summarizes recent data and discusses potential mechanisms. Evidence acquisition The review is based on the authors’ knowledge of the field supplemented by a PubMed search using the terms seafood, fish oil, saturated fatty acids, omega-3 fatty acids, eicosapentaenoic acid, docosahexaenoic acid, polyunsaturated fatty acids, monounsaturated fatty acids, and ASCVD. Evidence synthesis We mainly discuss the recent clinical trials that examine the effects of different types of dietary fatty acids and pharmacological use of n-3 PUFA products on ASCVD prevention and the potential mechanisms. Conclusions While replacement of dietary saturated fat with unsaturated fat, polyunsaturated fat in particular, or intake of LC n-3 PUFA–rich seafood has generally shown benefit for ASCVD prevention and is recommended for cardiovascular benefits, data on effects of n-3 PUFA products on ASCVD health are inconsistent. However, recent clinical trials support benefits of prescription EPA in ASCVD prevention. n-3 PUFAs may contribute to ASCVD prevention through multiple mechanisms, including lowering plasma triglyceride levels, anti-inflammatory effects, antithrombotic effects, and effects on endothelial function.

scholarly journals Omega-3 Polyunsaturated Fatty Acids and the Intestinal Epithelium—A Review

Foods ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 199
Author(s):  
Luke A. Durkin ◽  
Caroline E. Childs ◽  
Philip C. Calder
Keyword(s):  
Fatty Acids ◽  
Epithelial Cells ◽  
Polyunsaturated Fatty Acids ◽  
Intestinal Barrier ◽  
In Vitro Models ◽  
Omega 3 ◽  
Alpha Linolenic Acid ◽  
Chemical Mediator ◽  
Anti Inflammatory

Epithelial cells (enterocytes) form part of the intestinal barrier, the largest human interface between the internal and external environments, and responsible for maintaining regulated intestinal absorption and immunological control. Under inflammatory conditions, the intestinal barrier and its component enterocytes become inflamed, leading to changes in barrier histology, permeability, and chemical mediator production. Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) can influence the inflammatory state of a range of cell types, including endothelial cells, monocytes, and macrophages. This review aims to assess the current literature detailing the effects of ω-3 PUFAs on epithelial cells. Marine-derived ω-3 PUFAs, eicosapentaenoic acid and docosahexaenoic acid, as well as plant-derived alpha-linolenic acid, are incorporated into intestinal epithelial cell membranes, prevent changes to epithelial permeability, inhibit the production of pro-inflammatory cytokines and eicosanoids and induce the production of anti-inflammatory eicosanoids and docosanoids. Altered inflammatory markers have been attributed to changes in activity and/or expression of proteins involved in inflammatory signalling including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator activated receptor (PPAR) α and γ, G-protein coupled receptor (GPR) 120 and cyclooxygenase (COX)-2. Effective doses for each ω-3 PUFA are difficult to determine due to inconsistencies in dose and time of exposure between different in vitro models and between in vivo and in vitro models. Further research is needed to determine the anti-inflammatory potential of less-studied ω-3 PUFAs, including docosapentaenoic acid and stearidonic acid.

scholarly journals Neonatal Mouse Gut Metabolites Influence Cryptosporidium parvum Infection in Intestinal Epithelial Cells

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. e02582-20
Author(s):  
Kelli L. VanDussen ◽  
Lisa J. Funkhouser-Jones ◽  
Marianna E. Akey ◽  
Deborah A. Schaefer ◽  
Kevin Ackman ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Epithelial Cells ◽  
Cryptosporidium Parvum ◽  
Intestinal Epithelial Cells ◽  
Saturated Fatty Acids ◽  
Intestinal Lumen ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Long Chain

ABSTRACTThe protozoan parasite Cryptosporidium sp. is a leading cause of diarrheal disease in those with compromised or underdeveloped immune systems, particularly infants and toddlers in resource-poor localities. As an enteric pathogen, Cryptosporidium sp. invades the apical surface of intestinal epithelial cells, where it resides in close proximity to metabolites in the intestinal lumen. However, the effect of gut metabolites on susceptibility to Cryptosporidium infection remains largely unstudied. Here, we first identified which gut metabolites are prevalent in neonatal mice when they are most susceptible to Cryptosporidium parvum infection and then tested the isolated effects of these metabolites on C. parvum invasion and growth in intestinal epithelial cells. Our findings demonstrate that medium or long-chain saturated fatty acids inhibit C. parvum growth, perhaps by negatively affecting the streamlined metabolism in C. parvum, which is unable to synthesize fatty acids. Conversely, long-chain unsaturated fatty acids enhanced C. parvum invasion, possibly by modulating membrane fluidity. Hence, gut metabolites, either from diet or produced by the microbiota, influence C. parvum growth in vitro and may also contribute to the early susceptibility to cryptosporidiosis seen in young animals.IMPORTANCECryptosporidium sp. occupies a unique intracellular niche that exposes the parasite to both host cell contents and the intestinal lumen, including metabolites from the diet and produced by the microbiota. Both dietary and microbial products change over the course of early development and could contribute to the changes seen in susceptibility to cryptosporidiosis in humans and mice. Consistent with this model, we show that the immature gut metabolome influenced the growth of Cryptosporidium parvumin vitro. Interestingly, metabolites that significantly altered parasite growth were fatty acids, a class of molecules that Cryptosporidium sp. is unable to synthesize de novo. The enhancing effects of polyunsaturated fatty acids and the inhibitory effects of saturated fatty acids presented in this study may provide a framework for future studies into this enteric parasite’s interactions with exogenous fatty acids during the initial stages of infection.

scholarly journals Effect of Different Types of Dietary Fatty Acids on Subclinical Inflammation in Humans

2013 ◽  
pp. 145-152 ◽  
Author(s):  
I. KRÁLOVÁ LESNÁ ◽  
P. SUCHÁNEK ◽  
E. BRABCOVÁ ◽  
J. KOVÁŘ ◽  
H. MALÍNSKÁ ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Systemic Inflammation ◽  
Molecular Mechanisms ◽  
Statistical Significance ◽  
Saturated Fatty Acids ◽  
Dietary Fatty Acids ◽  
Low Density ◽  
Pufa Diet

Replacing SAFAs (saturated fatty acids) for vegetable PUFAs (polyunsaturated fatty acids) has a well documented positive effect on the lipoprotein pattern while the direct effect of dietary fatty acids composition on systemic inflammation remains to be proven. In well controlled randomised cross-over study with 15 overweight/obese postmenopausal women, the effect of dietary switch on systemic inflammation was investigated. A two 3 weeks dietary period either with predominant animal fat (SAFA, 29 caloric % SAFA) or vegetable fat (PUFA 25 % caloric % PUFA) were interrupted by wash-out period. The expected increasing effect on SAFA diet to LDL-C (low density cholesterol) and opposite effect of PUFA diet was documented following changes in fatty acid spectrum in VLDL (very low density cholesterol) particles. The switch from SAFA diet to PUFA diet produced a significant change of CRP (C-reactive protein) concentration (p<0.01) whereas similar trend of IL-18 did not reach statistical significance. In this study, previous in vitro results of different SAFA and PUFA proinflammatory effects with well documented molecular mechanisms were first proven in a clinical study. It could be stated that the substantial change of dietary fatty acid composition might influence proinflammatory effect in addition to traditional cardiovascular risk factors.

SER-287, AN INVESTIGATIONAL MICROBIOME THERAPEUTIC FOR PATIENTS WITH ACTIVE MILD-TO-MODERATE ULCERATIVE COLITIS, PRODUCES REMISSION ASSOCIATED METABOLITES, REDUCES INTESTINAL EPITHELIAL IL-8 SECRETION AND PROTECTS EPITHELIAL BARRIER FUNCTION IN VITRO

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S41-S42
Author(s):  
Asunción Martínez ◽  
Divya Balasubramanian ◽  
Ambar Piña ◽  
Karen Kieser ◽  
Priyanka Narendar ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fatty Acids ◽  
Epithelial Cells ◽  
Epithelial Barrier ◽  
Epithelial Integrity ◽  
Tnf Α ◽  
Phase 1B ◽  
Ifn Γ ◽  
Culture Supernatants

Abstract Background In a Phase 1b study of mild-to-moderate ulcerative colitis (UC) (Henn et al. Gastro 2020), oral daily dosing of SER-287, a purified consortium of Firmicutes spores administered after vancomycin pre-conditioning, led to significantly higher rates of clinical remission compared to placebo (40% versus 0%, respectively; p=0.024). Engraftment, defined as SER-287 spore germination and growth of metabolically-active bacteria, was associated with remission and shifts in disease relevant microbe-associated metabolites. To better understand the mechanism underlying these favorable clinical observations, we evaluated metabolite production by SER-287 and their impact on specific inflammatory pathways and barrier epithelial integrity in vitro. Methods Three SER-287 lots and a negative control pro-inflammatory consortium including three strains isolated from UC subjects (Escherichia coli, Bifidobacterium dentium, and Streptococcus parasanguinis) were grown in vitro in a complex medium designed to mimic the nutrient composition found in the human colon. Culture supernatants were assessed for the presence of anti-inflammatory and remission associated metabolites by GC-MS or LC-MS. Anti- and pro-inflammatory activities were determined by measuring IL-8 secretion, an inflammatory cytokine whose expression is elevated in UC patients, by HT29 epithelial cells after incubation with bacterial supernatants in the presence or absence of TNF-α. Epithelial integrity was assayed by measuring FITC-dextran leakage in a trans-well culture of differentiated primary human colonic epithelial cells challenged with IFN-γ in the presence or absence of culture supernatants. Results When cultured in vitro, all SER-287 lots tested produced the anti-inflammatory short-chain fatty acids butyrate and propionate and other metabolites associated with remission in the Phase 1b trial, including tryptophan metabolites, bile acids and medium-chain fatty acids. SER-287 culture supernatants significantly reduced IL-8 secretion in TNF-α stimulated HT29 cells while the pro-inflammatory consortium increased IL-8 secretion compared to TNF-α alone (Figure 1A). SER-287 lots induced minimal IL-8 secretion in the absence of TNF-α while the pro-inflammatory consortium strongly induced IL-8 (Figure 1B). SER-287 supernatants significantly decreased IFN-γ-mediated barrier disruption, while the pro-inflammatory consortium was not protective (Figure 2). Conclusions Production of remission-associated metabolites, reduction of epithelial inflammation, and protection from epithelial barrier damage are shown to be pharmacological properties of SER-287 which may underlie the mechanism of action of this microbiome therapeutic for mild-to-moderate UC.

scholarly journals Effects of Dietary n–3 and n–6 Polyunsaturated Fatty Acids in Inflammation and Cancerogenesis

2021 ◽  
Vol 22 (13) ◽  
pp. 6965
Author(s):  
Kamila P. Liput ◽  
Adam Lepczyński ◽  
Magdalena Ogłuszka ◽  
Agata Nawrocka ◽  
Ewa Poławska ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Epidemiological Studies ◽  
Omega 3 ◽  
Metabolic Disturbances ◽  
Cancer Models ◽  
Omega 6 ◽  
3 Omega

The dietary recommendation encourages reducing saturated fatty acids (SFA) in diet and replacing them with polyunsaturated fatty acids (PUFAs) n–3 (omega–3) and n–6 (omega–6) to decrease the risk of metabolic disturbances. Consequently, excessive n–6 PUFAs content and high n–6/n–3 ratio are found in Western-type diet. The importance of a dietary n–6/n–3 ratio to prevent chronic diseases is linked with anti-inflammatory functions of linolenic acid (ALA, 18:3n–3) and longer-chain n–3 PUFAs. Thus, this review provides an overview of the role of oxylipins derived from n–3 PUFAs and oxylipins formed from n–6 PUFAs on inflammation. Evidence of PUFAs’ role in carcinogenesis was also discussed. In vitro studies, animal cancer models and epidemiological studies demonstrate that these two PUFA groups have different effects on the cell growth, proliferation and progression of neoplastic lesions.

The Effects of Omega-3 Polyunsaturated Fatty Acids on TNF-α and IL-10 Secretion by Murine Peritoneal Cells In Vitro

Lipids ◽  
2007 ◽  
Vol 42 (8) ◽  
pp. 699-706 ◽  
Author(s):  
Ingibjorg H. Skuladottir ◽  
Dagbjort H. Petursdottir ◽  
Ingibjorg Hardardottir
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Omega 3 ◽  
Peritoneal Cells ◽  
Tnf Α

Dietary supplementation with omega-3 polyunsaturated fatty acids ameliorates acute pneumonia induced byKlebsiella pneumoniaein BALB/c mice

2013 ◽  
Vol 59 (7) ◽  
pp. 503-510 ◽  
Author(s):  
Sonica Sharma ◽  
Sanjay Chhibber ◽  
Harsh Mohan ◽  
Saroj Sharma
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Interleukin 1 ◽  
Bacterial Load ◽  
Dietary Fatty Acids ◽  
Omega 3 ◽  
Necrosis Factor Alpha ◽  
Pufa Supplementation ◽  
Acute Pneumonia

The immune benefits associated with the optimal intake of dietary fatty acids are widely known. The objective of the present investigation was to elucidate the role of omega-3 polyunsaturated fatty acids (n-3 PUFA) food source on acute pneumonia induced by Klebsiella pneumoniae. Three different n-3 PUFA preparations (cod liver oil, Maxigard, and flaxseed oil) were orally supplemented and infection was induced in different groups of experimental mice. Mice fed olive oil and normal saline served as oil and saline controls, respectively. After 2 weeks of fatty acid feeding, no effect on the establishment of infection was observed when acute pneumonia was induced in animals. On the other hand, 6 weeks of n-3 PUFA administration was found to improve resistance in mice, as reduced lung bacterial load coupled with significant improvement in pathology was seen in infected mice. Alveolar macrophages collected from all 3 groups of mice fed n-3 PUFA exhibited a significant decrease in the level of apoptosis following infection with K. pneumoniae and an enhanced in vitro phagocytic potential for the pathogen. Lower lung levels of nitric oxide, malondialdehyde, and lactate dehydrogenase were associated with a decrease in the severity of tissue damage. There was a significant increase in the lung levels of pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β)). No significant change was observed in the levels of interleukin-10 (IL-10). This study highlights that dietary n-3 PUFA supplementation exerts an overall beneficial effect against acute experimental pneumonia. This mechanism is operative through upregulation of nonspecific and specific immune defenses of the host.

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