scholarly journals Sex-Specific Differences in Resolution of Airway Inflammation in Fat-1 Transgenic Mice Following Repetitive Agricultural Dust Exposure

2022 ◽  
Vol 12 ◽  
Author(s):  
Arzu Ulu ◽  
Jalene V. Velazquez ◽  
Abigail Burr ◽  
Stefanie N. Sveiven ◽  
Jun Yang ◽  
...  

In agriculture industries, workers are at increased risk for developing pulmonary diseases due to inhalation of agricultural dusts, particularly when working in enclosed confinement facilities. Agricultural dusts inhalation leads to unresolved airway inflammation that precedes the development and progression of lung disease. We have previously shown beneficial effects of the omega-3 polyunsaturated fatty acid (ω-3 PUFA) DHA in protecting against the negative inflammatory effects of repetitive dust exposure in the lung. Dietary manipulation of pulmonary disease risk is an attractive and timely approach given the contribution of an increased ω-6 to ω-3 PUFA ratio to low grade inflammation and chronic disease in the Western diet. To prevent any confounding factors that comes with dietary supplementation of ω-3 PUFA (different sources, purity, dose, and duration), we employed a Fat-1 transgenic mouse model that convert ω-6 PUFA to ω-3 PUFA, leading to a tissue ω-6 to ω-3 PUFA ratio of approximately 1:1. Building on our initial findings, we hypothesized that attaining elevated tissue levels of ω-3 PUFA would attenuate agricultural dust-induced lung inflammation and its resolution. To test this hypothesis, we compared wild-type (WT) and Fat-1 transgenic mice in their response to aqueous extracts of agricultural dust (DE). We also used a soluble epoxide hydrolase inhibitor (sEH) to potentiate the effects of ω-3 PUFA, since sEH inhibitors have been shown to stabilize the anti-inflammatory P450 metabolites derived from both ω-3 and ω-6 PUFA and promote generation of specialized pro-resolving lipid mediators from ω-3 PUFA. Over a three-week period, mice were exposed to a total of 15 intranasal instillations of DE obtained from swine confinement buildings in the Midwest. We observed genotype and sex-specific differences between the WT vs. Fat-1 transgenic mice in response to repetitive dust exposure, where three-way ANOVA revealed significant main effects of treatment, genotype, and sex. Also, Fat-1 transgenic mice displayed reduced lymphoid aggregates in the lung following DE exposure as compared to WT animals exposed to DE, suggesting improved resilience to the DE-induced inflammatory effects. Overall, our data implicate a protective role of ω-3 FA in the lung following repetitive dust exposure.

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 334
Author(s):  
Hannah Land Lail ◽  
Rafaela G. Feresin ◽  
Dominique Hicks ◽  
Blakely Stone ◽  
Emily Price ◽  
...  

Inflammation that accompanies obesity is associated with the infiltration of metabolically active tissues by inflammatory immune cells. This propagates a chronic low-grade inflammation associated with increased signaling of common inflammatory pathways such as NF-κB and Toll-like receptor 4 (TLR4). Obesity-associated inflammation is linked to an increased risk of chronic diseases, including type 2 diabetes, cardiovascular disease, and cancer. Preclinical rodent and cell culture studies provide robust evidence that berries and their bioactive components have beneficial effects not only on inflammation, but also on biomarkers of many of these chronic diseases. Berries contain an abundance of bioactive compounds that have been shown to inhibit inflammation and to reduce reactive oxygen species. Therefore, berries represent an intriguing possibility for the treatment of obesity-induced inflammation and associated comorbidities. This review summarizes the anti-inflammatory properties of blackberries, blueberries, strawberries, and raspberries. This review highlights the anti-inflammatory mechanisms of berries and their bioactive components that have been elucidated through the use of preclinical models. The primary mechanisms mediating the anti-inflammatory effects of berries include a reduction in NF-κB signaling that may be secondary to reduced oxidative stress, a down-regulation of TLR4 signaling, and an increase in Nrf2.


Author(s):  
Shahieda Adams ◽  
Andreas Lopata ◽  
Cornelius Smuts ◽  
Roslynn Baatjies ◽  
Mohamed Jeebhay

Recent studies have highlighted the potential protective role of omega-3 polyunsaturated fatty acids (n-3 PUFA) in asthma. This study aimed at determining the association between seafood intake, serum PUFA composition and clinical endpoints of asthma in adults. A cross-sectional study of 642 subjects used the European Committee Respiratory Health Survey (ECRHS) questionnaire, skin prick tests, spirometry and methacholine challenge tests following ATS guidelines. Sera was analysed for n-3 and n-6 PUFA composition. Subjects had a mean age of 34 years, were largely female (65%) and 51% were current smokers. While 99% reported fish consumption, rock lobster, mussels, squid and abalone were also consumed less frequently. The prevalence of asthma symptoms was 11%, current asthma (ECRHS definition) was 8% and non-specific bronchial hyperresponsiveness (NSBH) was much higher (26%) In adjusted models the n-3 PUFAs 20:5 (EPA) and 22:5 (DPA) were significantly associated with a decreased risk of having NSBH. Total n-3 PUFA composition was associated with decreased NSBH risk (OR = 0.92), while high n-6 PUFA composition was associated with an increased risk (OR = 1.14).


Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1504 ◽  
Author(s):  
Cristina Carresi ◽  
Micaela Gliozzi ◽  
Vincenzo Musolino ◽  
Miriam Scicchitano ◽  
Federica Scarano ◽  
...  

Metabolic syndrome (MetS) represents a set of clinical findings that include visceral adiposity, insulin-resistance, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C) levels and hypertension, which is linked to an increased risk of developing type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). The pathogenesis of MetS involves both genetic and acquired factors triggering oxidative stress, cellular dysfunction and systemic inflammation process mainly responsible for the pathophysiological mechanism. In recent years, MetS has gained importance due to the exponential increase in obesity worldwide. However, at present, it remains underdiagnosed and undertreated. The present review will summarize the pathogenesis of MetS and the existing pharmacological therapies currently used and focus attention on the beneficial effects of natural compounds to reduce the risk and progression of MetS. In this regard, emerging evidence suggests a potential protective role of bergamot extracts, in particular bergamot flavonoids, in the management of different features of MetS, due to their pleiotropic anti-oxidative, anti-inflammatory and lipid-lowering effects.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Robert K. McNamara ◽  
Ronald Jandacek ◽  
Therese Rider ◽  
Patrick Tso ◽  
Yogesh Dwivedi ◽  
...  

Deficiency in long-chain omega-3 (LCn − 3) fatty acids, eicosapentaenoic acid (EPA, 20:5n − 3) and docosahexaenoic acid (DHA, 22:6n − 3), has been implicated in the pathoetiology of cardiovascular disease, a primary cause of excess premature mortality in patients with schizophrenia (SZ). In the present study, we determined erythrocyte EPA + DHA levels in adult medication-free patients SZ (n=20) and age-matched healthy controls (n=24). Erythrocyte EPA + DHA composition exhibited by SZ patients (3.5%) was significantly lower than healthy controls (4.5%, −22%, P=0.007). The majority of SZ patients (72%) exhibited EPA+DHA levels ≤4.0% compared with 37% of controls (Chi-square, P=0.001). In contrast, the omega-6 fatty acid arachidonic acid (AA, 20:4n−6) (+9%, P=0.02) and the AA:EPA + DHA ratio (+28%, P=0.0004) were significantly greater in SZ patients. Linoleic acid (18:2n−6) was significantly lower (−12%, P=0.009) and the erythrocyte 20:3/18:2 ratio (an index of delta6-desaturase activity) was significantly elevated in SZ patients. Compared with same-gender controls, EPA + DHA composition was significantly lower in male (−19%, P=0.04) but not female (−13%, P=0.33) SZ patients, whereas the 20:3/18:2 ratio was significantly elevated in both male (+22%, P=0.008) and female (+22%, P=0.04) SZ patients. These results suggest that the majority of SZ patients exhibit low LCn − 3 fatty acid levels which may place them at increased risk for cardiovascular morbidity and mortality.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 330
Author(s):  
Adam Lepczyński ◽  
Małgorzata Ożgo ◽  
Katarzyna Michałek ◽  
Alicja Dratwa-Chałupnik ◽  
Marta Grabowska ◽  
...  

Westernized diet is characterized by a high content of saturated fatty acids (SFA) and a low level of omega-3 polyunsaturated fatty acids (PUFA), often accompanied by an imbalance in the omega-6/omega-3 PUFA ratio. Since increased intake of SFA and n-6 PUFA is considered as a cardiovascular disease risk factor, this study was conducted to determine whether a three-month dietary supplementation of high-fat diets (HFDs) with saturated fatty acids and a significant proportion of various n-6 and n-3 PUFA ratios would affect the architecture and protein expression patterns of the murine heart. Therefore, three HFD (n = 6) feeding groups: rich in SFA, dominated by PUFA with the n-6/n-3–14:1, and n-6/n-3–5:1, ratios were compared to animals fed standard mouse chow. For this purpose, we performed two-dimensional electrophoresis with MALDI-ToF mass spectrometry-based identification of differentially expressed cardiac proteins, and a histological examination of cardiac morphology. The results indicated that mice fed with all HFDs developed signs of hypertrophy and cardiac fibrosis. Animals fed SFA-rich HFD manifested the most severe cardiac hypertrophy and fibrosis lesions, whereas less pronounced changes were observed in the group of animals that ingested the highest amount of omega-3 FA. In general, all HFDs, regardless of FA composition, evoked a comparable pattern of cardiac protein changes and affected the following biological processes: lipid metabolism and FA β-oxidation, glycolysis, TCA cycle, respiratory chain, myocardium contractility, oxidative stress and PUFA eicosanoid metabolism. However, it should be noted that three proteins, namely IDH3A, LDHB, and AK1, were affected differently by various FA contents. High expression of these myocardial proteins found in the group of animals fed a HFD with the highest n-3 PUFA content could be closely related to the observed development of hypertrophy.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Simone Isling Pærregaard ◽  
Marianne Agerholm ◽  
Annette Karen Serup ◽  
Tao Ma ◽  
Bente Kiens ◽  
...  

Free fatty acid receptor-4 (FFAR4), also known as GPR120, has been reported to mediate the beneficial effects of omega-3 polyunsaturated fatty acids (ω3-PUFAs) by inducing an anti-inflammatory immune response. Thus, activation of FFAR4 has been reported to ameliorate chronic low-grade inflammation and insulin resistance accompanying obesity. However, conflicting reports on the role of FFAR4 in mediating the effects ofω3-PUFAs are emerging, suggesting that FFAR4 may not be the sole effector. Hence analyses of the importance of this receptor in relation to other signaling pathways and prominent effects ofω3-PUFAs remain to be elucidated. In the present study, we usedFfar4knockouts (KO) and heterozygous (HET) mice fed either low fat, low sucrose reference diet; high fat, high sucroseω3-PUFA; or high fat, high sucroseω6-PUFA diet for 36 weeks. We demonstrate that both KO and HET mice fedω3-PUFAs were protected against obesity, hepatic triacylglycerol accumulation, and whole-body insulin resistance. Moreover,ω3-PUFA fed mice had increased circulating protein levels of the anti-inflammatory adipokine, adiponectin, decreased fasting insulin levels, and decreased mRNA expression of several proinflammatory molecules within visceral adipose tissue. In conclusion, we find that FFAR4 signaling is not required for the reported anti-inflammatory and insulin-sensitizing effects mediated byω3-PUFAs.


Author(s):  
Carla J. Olave ◽  
Kathleen M. Ivester ◽  
Laurent L. Couëtil ◽  
Jackeline Franco-Marmolejo ◽  
Abhijit Mukhopadhyay ◽  
...  

Abstract OBJECTIVE To investigate the role of omega-3 polyunsaturated fatty acids (Ω-3)–derived proresolving lipid mediators (PRLM) in the resolution of mild airway inflammation in horses. ANIMALS 20 horses with mild airway inflammation. PROCEDURES Horses previously eating hay were fed hay pellets (low Ω-3 content; n = 10) or haylage (high Ω-3 content; 9) for 6 weeks. Dust exposure was measured in the breathing zone with a real-time particulate monitor. Bronchoalveolar lavage (BAL) was performed at baseline, week 3, and week 6. The effect of PRLM on neutrophil apoptosis and efferocytosis was examined in vitro. BAL fluid inflammatory cell proportions, apoptosis of circulating neutrophils, efferocytosis displayed by alveolar macrophages, and plasma lipid concentrations were compared between groups fed low and high amounts of Ω-3 by use of repeated measures of generalized linear models. RESULTS Dust exposure was significantly higher with hay feeding, compared to haylage and pellets, and equivalent between haylage and pellets. BAL fluid neutrophil proportions decreased significantly in horses fed haylage (baseline, 11.8 ± 2.4%; week 6, 2.5 ± 1.1%) but not pellets (baseline, 12.1 ± 2.3%; week 6, 8.5% ± 1.7%). At week 6, horses eating haylage had significantly lower BAL neutrophil proportions than those eating pellets, and a significantly lower concentration of stearic acid than at baseline. PRLM treatments did not affect neutrophil apoptosis or efferocytosis. CLINICAL RELEVANCE Despite similar reduction in dust exposure, horses fed haylage displayed greater resolution of airway inflammation than those fed pellets. This improvement was not associated with increased plasma Ω-3 concentrations. Feeding haylage improves airway inflammation beyond that due to reduced dust exposure, though the mechanism remains unclear.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Akadiri Yessoufou ◽  
Magloire P. Nekoua ◽  
Adam Gbankoto ◽  
Yohana Mashalla ◽  
Kabirou Moutairou

Omega-3 polyunsaturated fatty acids (PUFAs) are increasingly being used to prevent cardiovascular diseases, including diabetes and obesity. In this paper, we report data on the observed effects of omega-3 PUFA on major metabolic disorders and immune system disruption during gestational diabetes and their consequences on macrosomia. While controversies still exist about omega-3 PUFA effects on antioxidant status regarding the level of omega-3 PUFA in diet supplementation, their lipid-lowering effects are unanimously recognized by researchers. Animal studies have shown that omega-3 PUFA contributes to the maintenance of the immune defense system by promoting the differentiation of T helper (Th) cell to a Th2 phenotype in diabetic pregnancy and by shifting the Th1/Th2 ratio from a deleterious proinflammatory Th1 phenotype to a protective anti-inflammatory Th2 phenotype in macrosomia and in adulthood obesity that results from macrosomia at birth. Based on the available evidence, international nutritional and food agencies recommend administration of omega-3 PUFA as triglyceride-lowering agents, for the prevention of cardiovascular disease risk and during human pregnancy and lactation. Furthermore, studies targeting humans are still required to explore application of the fatty acids as supplement in the management of gestational diabetes and inflammatory and immune diseases.


Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1194 ◽  
Author(s):  
Salvador Fernández-Arroyo ◽  
Anna Hernández-Aguilera ◽  
Marijke A. de Vries ◽  
Benjamin Burggraaf ◽  
Ellen van der Zwan ◽  
...  

Postprandial lipemia can lead to an accumulation of atherogenic lipoproteins in the circulation associated with systemic low-grade inflammation and an increased risk of cardiovascular disease. Lifestyle and pharmacological treatments are usually prescribed for prevention. Vitamin D3 (cholecalciferol), as an anti-atherogenic agent, is being taken into consideration due to its potential beneficial effects in lipid metabolism and its anti-inflammatory potency. To assess the effects of vitamin D3 in the postprandial lipid profile in obese, vitamin D-deficient women, a non-targeted lipidomics approach using liquid chromatography coupled to a quadrupole time-of flight mass spectrometer was used to identify and quantitate a wide-range of circulating lipid species, including diglycerides, lysophosphatidylcholines, phosphatidylcholines, phosphatidylethanolamines, sphingomyelins and triglycerides. The most important changes were found in plasmatic sphingomyelin levels, which experience a decrease after vitamin D3 intake. Our results suggest a turnover of sphingomyelins, probably due to an increased activity of neutral sphingomyelinases, and, therefore, with implications in the clearance of chylomicrons, LDL and VLDL, decreasing postprandial inflammation and macrophage adherence to endothelia, potentially improving cardiovascular disease risk.


2016 ◽  
Vol 3 (2) ◽  
Author(s):  
Dr. Meena Jain ◽  
Saloni Chandalia

This research paper deals with the Family Environment and its Correlation with Anxiety and Depression level among persons with Heart Disease. There had been a number of researches that investigated that ischemic heart disease patients who suffer significant anxiety have close to a 5-fold increased risk of experiencing frequent angina and those with depression have more than a 3-fold increased risk for these episodes. This observed link between psychiatric symptoms and angina underlines the importance of treating anxiety and depression in cardiac patients, according to study co author Dr Mark D Sullivan (University of Washington School of Medicine, Seattle). To gather the needed data, Hamilton Anxiety Scale and Becks Depression Inventory were used. As stated from literatures, for people with heart dysfunction, depression and anxiety can increase the risk of an adverse cardiac event such as a heart attack or blood clots. For people who do not have heart disease, depression and anxiety can also increase the risk of a heart attack and development of coronary artery disease. Researchers have also emphasized on the role of family psychosocial environment and its positive association with the Coronary Heart Disease risk.


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