RESUMO
Mast cells (MCs) play critical roles in the establishment of allergic diseases. We recently demonstrated an unexpected, proinflammatory role for IL-10 in regulating MC responses. IL-10 enhanced MC activation and promoted IgE-dependent responses during food allergy. However, whether these effects extend to IgE-independent stimuli is not clear. In this article, we demonstrate that IL-10 plays a critical role in driving IL-33-mediated MC responses. IL-10 stimulation enhanced MC expansion and degranulation, ST2 expression, IL-13 production, and phospho-relA upregulation in IL-33-treated cells while suppressing TNF-α. These effects were partly dependent on endogenous IL-10 and further amplified in MCs coactivated with both IL-33 and IgE/Ag. IL-10's divergent effects also extended in vivo. In a MC-dependent model of IL-33-induced neutrophilia, IL-10 treatment enhanced MC responsiveness, leading to suppression of neutrophils and decreased TNF-α. In contrast, during IL-33-induced type 2 inflammation, IL-10 priming exacerbated MC activity, resulting in MC recruitment to various tissues, enhanced ST2 expression, induction of hypothermia, recruitment of eosinophils, and increased MCPT-1 and IL-13 levels. Our data elucidate an important role for IL-10 as an augmenter of IL-33-mediated MC responses, with implications during both allergic diseases and other MC-dependent disorders. IL-10 induction is routinely used as a prognostic marker of disease improvement. Our data suggest instead that IL-10 can enhance ST2 responsiveness in IL-33-activated MCs, with the potential to both aggravate or suppress disease severity depending on the inflammatory context.
Assuntos
Hipersensibilidade Alimentar , Mastócitos , Humanos , Mastócitos/metabolismo , Interleucina-10/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Imunoglobulina E/metabolismo , Interleucina-33/metabolismo , Interleucina-13/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Inflamação/metabolismo , Degranulação CelularRESUMO
Oral and gut Bacteroidetes produce unique classes of serine-glycine lipodipeptides and glycine aminolipids that signal through host Toll-like receptor 2. These glycine lipids have also been detected in human arteries, but their effects on atherosclerosis are unknown. Here, we sought to investigate the bioactivity of bacterial glycine lipids in mouse models of atherosclerosis. Lipid 654 (L654), a serine-glycine lipodipeptide species, was first tested in a high-fat diet (HFD)-fed Ldlr-/- model of atherosclerosis. Intraperitoneal administration of L654 over 7 weeks to HFD-fed Ldlr-/- mice resulted in hypocholesterolemic effects and significantly attenuated the progression of atherosclerosis. We found that L654 also reduced liver inflammatory and extracellular matrix gene expression, which may be related to inhibition of macrophage activation as demonstrated in vivo by lower major histocompatibility complex class II gene expression and confirmed in cell experiments. In addition, L654 and other bacterial glycine lipids in feces, liver, and serum were markedly reduced alongside changes in Bacteroidetes relative abundance in HFD-fed mice. Finally, we tested the bioactivities of L654 and related lipid 567 in chow-fed Apoe-/- mice, which displayed much higher fecal glycine lipids relative to HFD-fed Ldlr-/- mice. Administration of L654 or lipid 567 for 7 weeks to these mice reduced the liver injury marker alanine aminotransferase, but other effects seen in Ldlr-/- were not observed. Therefore, we conclude that conditions in which gut microbiome-derived glycine lipids are lost, such as HFD, may exacerbate the development of atherosclerosis and liver injury, whereas correction of such depletion may protect from these disorders.
Assuntos
Aterosclerose , Microbioma Gastrointestinal , Animais , Aterosclerose/genética , Bactérias , Bacteroidetes , Dieta Hiperlipídica/efeitos adversos , Glicina/farmacologia , Fígado , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , SerinaRESUMO
Cytokines are small secreted proteins released by different types of cells with specific effects on cellular signaling and communication via binding to their receptors on the cell surface. IL-10 is known to be a pleiotropic and potent anti-inflammatory and immunosuppressive cytokine that is produced by both innate and adaptive immunity cells including dendritic cells, macrophages, mast cells, natural killer cells, eosinophils, neutrophils, B cells, CD8+ T cells, and TH1, TH2, and TH17 and regulatory T cells. Both direct and indirect activation of the stress axis promotes IL-10 secretion. IL-10 deregulation plays a role in the development of a large number of inflammatory diseases such as neuropathic pain, Parkinson's disease, Alzheimer's disease, osteoarthritis, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, type 1 diabetes, inflammatory bowel disease, and allergy. Curcumin is a natural anti-inflammatory compound able to induce the expression and production of IL-10 and enhancing its action on a large number of tissues. In vitro and in pre-clinical models curcumin is able to modulate the disease pathophysiology of conditions such as pain and neurodegenerative diseases, bowel inflammation, and allergy, but also of infections and cancer through its effect on IL-10 secretion. In humans, at least one part of the positive effects of curcumin on health could be related to its ability to enhance IL-10 -mediated effects.
Assuntos
Curcumina/farmacologia , Imunomodulação/efeitos dos fármacos , Interleucina-10/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-10/genéticaRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver diseases, and is closely related to metabolic syndrome and its related conditions, diabetes mellitus and dyslipidemia. On the other hand, NAFLD as a multisystem disease increases the risk of several chronic diseases include type 2 diabetes mellitus, cardiovascular disease (CVD), and chronic kidney disease. The main objective was to review the efficacy of bioactive natural compounds assessed by clinical trials. Search literature using four databases (PubMed, EBSCO, Web of Science, and Ovid Medline) to review publications that focused on the impact of bioactive natural compounds in NAFLD treatment. Due to the lack of effective pharmacological treatments available for NAFLD, lifestyle modifications such as following a healthy diet, vigorous physical activity, and weight reduction remain the first line of treatment for NAFLD. However, due to the poor adherence to this type of treatment, especially for long-term weight loss diets some of which may have harmful effects on the liver, finding novel therapeutic agents for NAFLD treatment and/or preventing NAFLD progression has garnered significant interest. Although the therapeutic agents of NAFLD treatment have been reviewed previously, to date, no summary has been conducted of clinical trials examining the effects of herbal compounds on NAFLD-related biomarkers. This review highlights the beneficial role of herbal bioactives and medicinal plants in NAFLD treatment, particularly as complementary to a healthy lifestyle. All natural products described in this review seem to have some benefits to improve oxidative stress, cellular inflammation and insulin-resistance, which always remain as the "primum movens" of NAFLD pathogenesis.
Assuntos
Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Fitoterapia , Preparações de Plantas/uso terapêutico , Plantas Medicinais , Animais , HumanosRESUMO
BACKGROUND: Habitual consumption of eggs has been hypothesized to positively modify biomarkers of cardiovascular disease risk through proposed antioxidant properties. OBJECTIVES: To examine this relationship, 50 young, healthy men and women were enrolled into a randomized crossover clinical intervention. METHODS: Participants consumed either 2 eggs per day or one packet of oatmeal a day for 4 weeks, followed by a 3-week wash-out and crossed over to the alternate breakfast. Fasting blood samples and peripheral blood mononuclear cells (PBMCs) were collected at the end of each intervention period. RESULTS: Increases in plasma large high-density lipoprotein (HDL) and large low-density lipoprotein (LDL) particle concentrations as measured by nuclear magnetic resonance were found following egg consumption (p < 0.001, p < 0.05), respectively, with increases in apolipoprotein concentration as well (p < 0.05). Though there was no difference in the intake of antioxidants lutein and zeaxanthin, a significant increase in plasma concentrations of these carotenoids was observed (p < 0.001) after egg consumption. There was no change in lecithin-cholesterol acyl transferase, cholesteryl ester transfer protein, or paroxanase-1 arylesterase activities between breakfast interventions. Dietary and plasma choline were both higher following egg consumption compared to oatmeal consumption (p < 0.001); however, there was no change in plasma trimethylamine N-oxide (TMAO) concentrations. Two eggs per day had no impact on PBMC gene expression related to cholesterol metabolism, oxidation, or TMAO production. CONCLUSIONS: These results suggest that compared to oatmeal, consumption of 2 eggs for breakfast provided increased plasma carotenoids and improved biomarkers of cardiovascular disease (CVD) risk while not affecting TMAO levels in this population.
Assuntos
Avena , Desjejum , Carotenoides/sangue , Colina/sangue , Ovos , Metilaminas/sangue , Adolescente , Adulto , Antioxidantes/administração & dosagem , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Colesterol/genética , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Colina/administração & dosagem , Estudos Cross-Over , Dieta , Feminino , Expressão Gênica , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Fatores de RiscoRESUMO
Background: HDL function may be more important than HDL concentration in determining risk for cardiovascular disease. In addition, HDL is a carrier of carotenoids and antioxidant enzymes, which protect HDL and LDL particles against oxidation.Objective: The goal of this study was to determine the impact of consuming 0-3 eggs/d on LDL and HDL particle size, HDL function, and plasma antioxidants in a young, healthy population.Methods: Thirty-eight healthy men and women [age 18-30 y, body mass index (in kg/m2) 18.5-29.9] participated in this 14-wk crossover intervention. Subjects underwent a 2-wk washout (0 eggs/d) followed by sequentially increasing intake of 1, 2, and 3 eggs/d for 4 wk each. After each period, fasting blood was collected for analysis of lipoprotein subfractions, plasma apolipoprotein (apo) concentration, lutein and zeaxanthin concentration, and activities of lecithin-cholesterol acyltransferase, cholesteryl ester transfer protein, and paraoxonase-1.Results: Compared with intake of 0 eggs/d, consuming 1-3 eggs/d resulted in increased large-LDL (21-37%) and large-HDL (6-13%) particle concentrations, plasma apoAI (9-15%), and lecithin-cholesterol acyltransferase activity (5-15%) (P < 0.05 for all biomarkers). Intake of 2-3 eggs/d also promoted an 11% increase in apoAII (P < 0.05) and a 20-31% increase in plasma lutein and zeaxanthin (P < 0.05), whereas intake of 3 eggs/d resulted in a 9-16% increase in serum paraoxonase-1 activity compared with intake of 1-2 eggs/d (P < 0.05). Egg intake did not affect cholesteryl ester transfer protein activity.Conclusions: Intake of 1 egg/d was sufficient to increase HDL function and large-LDL particle concentration; however, intake of 2-3 eggs/d supported greater improvements in HDL function as well as increased plasma carotenoids. Overall, intake of ≤3 eggs/d favored a less atherogenic LDL particle profile, improved HDL function, and increased plasma antioxidants in young, healthy adults. This trial was registered at clinicaltrials.gov as NCT02531958.
Assuntos
Antioxidantes/metabolismo , HDL-Colesterol/sangue , Dieta , Ovos , Adolescente , Adulto , Apolipoproteínas/sangue , Apolipoproteínas/metabolismo , Arildialquilfosfatase/genética , Arildialquilfosfatase/metabolismo , HDL-Colesterol/fisiologia , Estudos Cross-Over , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Curcumin, a bioactive polyphenol, is a yellow pigment of the Curcuma longa (turmeric) plant. Curcumin has many pharmacologic effects including antioxidant, anti-carcinogenic, anti-obesity, anti-angiogenic and anti-inflammatory properties. Recently, it has been found that curcumin affects lipid metabolism, and subsequently, may alleviate hyperlipidemia and atherosclerosis. Plasma HDL cholesterol (HDL-C) is an independent negative risk predictor of cardiovascular disease (CVD). However, numerous clinical and genetic studies have yielded disappointing results about the therapeutic benefit of raising plasma HDL-C levels. Therefore, research efforts are now focused on improving HDL functionality, independent of HDL-C levels. The quality of HDL particles can vary considerably due to heterogeneity in composition. Consistent with its complexity in composition and metabolism, a wide range of biological activities is reported for HDL, including antioxidant, anti-glycation, anti-inflammatory, anti-thrombotic, anti-apoptotic and immune modulatory activities. Protective properties of curcumin may influence HDL functionality; therefore, we reviewed the literature to determine whether curcumin can augment HDL function. In this review, we concluded that curcumin may modulate markers of HDL function, such as apo-AI, CETP, LCAT, PON1, MPO activities and levels. Curcumin may subsequently improve conditions in which HDL is dysfunctional and may have potential as a therapeutic drug in future. Further clinical trials with bioavailability-improved formulations of curcumin are warranted to examine its effects on lipid metabolism and HDL function.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Curcumina/farmacologia , Lipoproteínas HDL/metabolismo , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/química , Antioxidantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Curcuma/química , Curcumina/química , Curcumina/uso terapêutico , Dislipidemias/tratamento farmacológico , Dislipidemias/metabolismo , Humanos , Lipoproteínas HDL/análiseRESUMO
To investigate the mechanisms by which Moringa oleifera leaves (ML) modulate hepatic lipids, guinea pigs were allocated to either control (0% ML), 10% Low Moringa (LM) or 15% High Moringa (HM) diets with 0.25% dietary cholesterol to induce hepatic steatosis. After 6 weeks, guinea pigs were sacrificed and liver and plasma were collected to determine plasma lipids, hepatic lipids, cytokines and the expression of genes involved in hepatic cholesterol (CH) and triglyceride (TG) metabolism. There were no differences in plasma lipids among groups. A dose-response effect of ML was observed in hepatic lipids (CH and TG) with the lowest concentrations in the HM group (p < 0.001), consistent with histological evaluation of lipid droplets. Hepatic gene expression of diglyceride acyltransferase-2 and peroxisome proliferator activated receptor-γ, as well as protein concentrations interleukin (IL)-1ß and interferon-γ, were lowest in the HM group (p < 0.005). Hepatic gene expression of cluster of differentiation-68 and sterol regulatory element binding protein-1c were 60% lower in both the LM and HM groups compared to controls (p < 0.01). This study demonstrates that ML may prevent hepatic steatosis by affecting gene expression related to hepatic lipids synthesis resulting in lower concentrations of cholesterol and triglycerides and reduced inflammation in the liver.
Assuntos
Fígado Gorduroso/prevenção & controle , Inflamação/prevenção & controle , Metabolismo dos Lipídeos , Moringa , Ração Animal/análise , Animais , Glicemia/metabolismo , Dieta , Ingestão de Alimentos , Fígado Gorduroso/sangue , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Regulação da Expressão Gênica , Cobaias , Inflamação/sangue , Inflamação/genética , Inflamação/metabolismo , Lipídeos/sangue , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Masculino , Moringa/químicaRESUMO
Studies in human populations have shown a significant correlation between procollagen C-endopeptidase enhancer protein 2 (PCPE2) single nucleotide polymorphisms and plasma HDL cholesterol concentrations. PCPE2, a 52-kDa glycoprotein located in the extracellular matrix, enhances the cleavage of C-terminal procollagen by bone morphogenetic protein 1 (BMP1). Our studies here focused on investigating the basis for the elevated concentration of enlarged plasma HDL in PCPE2-deficient mice to determine whether they protected against diet-induced atherosclerosis. PCPE2-deficient mice were crossed with LDL receptor-deficient mice to obtain LDLr(-/-), PCPE2(-/-) mice, which had elevated HDL levels compared with LDLr(-/-) mice with similar LDL concentrations. We found that LDLr(-/-), PCPE2(-/-) mice had significantly more neutral lipid and CD68+ infiltration in the aortic root than LDLr(-/-) mice. Surprisingly, in light of their elevated HDL levels, the extent of aortic lipid deposition in LDLr(-/-), PCPE2(-/-) mice was similar to that reported for LDLr(-/-), apoA-I(-/-) mice, which lack any apoA-I/HDL. Furthermore, LDLr(-/-), PCPE2(-/-) mice had reduced HDL apoA-I fractional clearance and macrophage to fecal reverse cholesterol transport rates compared with LDLr(-/-) mice, despite a 2-fold increase in liver SR-BI expression. PCPE2 was shown to enhance SR-BI function by increasing the rate of HDL-associated cholesteryl ester uptake, possibly by optimizing SR-BI localization and/or conformation. We conclude that PCPE2 is atheroprotective and an important component of the reverse cholesterol transport HDL system.
Assuntos
Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Ésteres do Colesterol/metabolismo , Glicoproteínas/metabolismo , Lipoproteínas HDL/metabolismo , Receptores Depuradores Classe B/metabolismo , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Aorta/metabolismo , Aorta/patologia , Apolipoproteína A-I/genética , Apolipoproteína A-I/metabolismo , Aterosclerose/induzido quimicamente , Aterosclerose/genética , Aterosclerose/patologia , Transporte Biológico Ativo/genética , Células CHO , Ésteres do Colesterol/genética , Cricetulus , Glicoproteínas/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Lipoproteínas HDL/genética , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Knockout , Receptores de LDL/genética , Receptores de LDL/metabolismo , Receptores Depuradores Classe B/genéticaRESUMO
BACKGROUND: It is not clear how oil-in-water nanoemulsions of lutein may affect bioavailability and consequently alter lipoprotein metabolism, oxidative stress, and inflammation. OBJECTIVE: The bioavailability as well as effects of a powdered lutein (PL) and an oil-in-water lutein nanoemulsion (NANO; particle size: 254.2 nm; polydispersity index: 0.29; and ζ-potential: -65 mV) on metabolic variables in liver, plasma, and adipose tissue in a guinea pig model of hepatic steatosis were evaluated. METHODS: Twenty-four 2-mo-old male Hartley guinea pigs, weighing 200-300 g (n = 8/group), were fed diets containing 0.25 g cholesterol/100 g to induce liver injury for the duration of the study. They were allocated to control (0 mg lutein), PL (3.5 mg/d), or NANO (3.5 mg/d) groups. After 6 wk, plasma, liver, and adipose tissue were collected for determination of lutein, plasma lipids, tissue cholesterol, and inflammatory cytokines. RESULTS: The NANO group had 2-fold higher concentrations of lutein in plasma (P < 0.001) and 1.6-fold higher concentrations in liver (P < 0.001) than did the PL group, indicating greater bioavailability of this carotenoid. The NANO group also had 24% lower hepatic steatosis scores (P < 0.05), 31% lower hepatic cholesterol accumulation (P < 0.05), and 64% lower plasma alanine aminotransferase (P < 0.05) than did the control group. Hepatic oxidized LDL was 55% lower in both the PL and NANO groups than in the control group (P < 0.05). In plasma, the NANO group had 2-fold higher concentrations of LDL and HDL cholesterol as well as a 2-fold higher number of VLDL, LDL, and HDL particles than did the other 2 groups as evaluated by nuclear magnetic resonance. Furthermore, the NANO group had 15% higher concentrations of free cholesterol in adipose tissue, resulting in higher concentrations of inflammatory markers, than did the other 2 groups. CONCLUSIONS: These results indicate that, although this lutein nanoemulsion exerted protective effects against hepatic steatosis, plasma lipoproteins and adipose tissue cholesterol were increased. These data suggest that the metabolic effects of this particular nanoemulsion might not be protective in all tissues in guinea pigs.
Assuntos
Fígado Gorduroso/tratamento farmacológico , Luteína/administração & dosagem , Luteína/farmacocinética , Substâncias Protetoras/administração & dosagem , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Modelos Animais de Doenças , Emulsões , Cobaias , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Pós , Substâncias Protetoras/farmacocinética , Triglicerídeos/sangueRESUMO
Dietary anthocyanins have been shown to reduce inflammation in animal models and may ameliorate obesity-related complications. Black elderberry is one of the richest sources of anthocyanins. We investigated the metabolic effects of anthocyanin-rich black elderberry extract (BEE) in a diet-induced obese C57BL/6J mouse model. Mice were fed either a low-fat diet (n 8), high-fat lard-based diet (HFD; n 16), HFD+0·25 % (w/w) BEE (0·25 %-BEE; n 16) or HFD+1·25 % BEE (1·25 %-BEE; n 16) for 16 weeks. The 0·25 % BEE (0·034 % anthocyanin, w/w) and 1·25 % BEE (0·17 % anthocyanin, w/w) diets corresponded to estimated anthocyanin doses of 20-40 mg and 100-200 mg per kg of body weight, respectively. After 16 weeks, both BEE groups had significantly lower liver weights, serum TAG, homoeostasis model assessment and serum monocyte chemoattractant protein-1 compared with HFD. The 0·25 %-BEE also had lower serum insulin and TNFα compared with HFD. Hepatic fatty acid synthase mRNA was lower in both BEE groups, whereas PPARγ2 mRNA and liver cholesterol were lower in 1·25 %-BEE, suggesting decreased hepatic lipid synthesis. Higher adipose PPARγ mRNA, transforming growth factor ß mRNA and adipose tissue histology suggested a pro-fibrogenic phenotype that was less inflammatory in 1·25 %-BEE. Skeletal muscle mRNA expression of the myokine IL-6 was higher in 0·25 %-BEE relative to HFD. These results suggest that BEE may have improved some metabolic disturbances present in this mouse model of obesity by lowering serum TAG, inflammatory markers and insulin resistance.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Inflamação/tratamento farmacológico , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Sambucus nigra/química , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Peso Corporal , Quimiocina CCL2/sangue , Dieta com Restrição de Gorduras , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Insulina/sangue , Resistência à Insulina , Interleucina-6/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
How the microbiome regulates responses of systemic innate immune cells is unclear. In the present study, our purpose was to document a novel mechanism by which the microbiome mediates crosstalk with the systemic innate immune system. We have identified a family of microbiome Bacteroidota-derived lipopeptides-the serine-glycine (S/G) lipids, which are TLR2 ligands, access the systemic circulation, and regulate proinflammatory responses of splenic monocytes. To document the role of these lipids in regulating systemic immunity, we used oral gavage with an antibiotic to decrease the production of these lipids and administered exogenously purified lipids to increase the systemic level of these lipids. We found that decreasing systemic S/G lipids by decreasing microbiome Bacteroidota significantly enhanced splenic monocyte proinflammatory responses. Replenishing systemic levels of S/G lipids via exogenous administration returned splenic monocyte responses to control levels. Transcriptomic analysis demonstrated that S/G lipids regulate monocyte proinflammatory responses at the level of gene expression of a small set of upstream inhibitors of TLR and NF-κB pathways that include Trem2 and Irf4. Consistent with enhancement in proinflammatory cytokine responses, decreasing S/G lipids lowered gene expression of specific pathway inhibitors. Replenishing S/G lipids normalized gene expression of these inhibitors. In conclusion, our results suggest that microbiome-derived S/G lipids normally establish a level of buffered signaling activation necessary for well-regulated innate immune responses in systemic monocytes. By regulating gene expression of inflammatory pathway inhibitors such as Trem2, S/G lipids merit broader investigation into the potential dysfunction of other innate immune cells, such as microglia, in diseases such as Alzheimer's disease.
Assuntos
Monócitos , Transdução de Sinais , Monócitos/imunologia , Monócitos/metabolismo , Monócitos/efeitos dos fármacos , Animais , Camundongos , Microbiota/imunologia , Camundongos Endogâmicos C57BL , Imunidade Inata , Receptor 2 Toll-Like/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Lipopeptídeos/farmacologia , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , NF-kappa B/metabolismo , Inflamação/imunologia , Fatores Reguladores de Interferon/metabolismo , Fatores Reguladores de Interferon/genética , Masculino , Lipídeos , Baço/imunologia , Baço/metabolismo , Citocinas/metabolismo , FemininoRESUMO
Lipid metabolism plays a major role in the regulation of the immune system. Exogenous (dietary and microbial-derived) and endogenous (non-microbial-derived) lipids play a direct role in regulating immune cell activation, differentiation and expansion, and inflammatory phenotypes. Understanding the complexities of lipid-immune interactions may have important implications for human health, as certain lipids or immune pathways may be beneficial in circumstances of acute infection yet detrimental in chronic inflammatory diseases. Further, there are key differences in the lipid effects between specific immune cell types and location (e.g., gut mucosal vs. systemic immune cells), suggesting that the immunomodulatory properties of lipids may be tissue-compartment-specific, although the direct effect of dietary lipids on the mucosal immune system warrants further investigation. Importantly, there is recent evidence to suggest that lipid-immune interactions are dependent on sex, metabolic status, and the gut microbiome in preclinical models. While the lipid-immune relationship has not been adequately established in/translated to humans, research is warranted to evaluate the differences in lipid-immune interactions across individuals and whether the optimization of lipid-immune interactions requires precision nutrition approaches to mitigate or manage disease. In this review, we discuss the mechanisms by which lipids regulate immune responses and the influence of dietary lipids on these processes, highlighting compelling areas for future research.
RESUMO
We evaluated the effects of grape polyphenols in individuals classified with metabolic syndrome (MetS). Men (n = 24) aged 30-70 y were randomly assigned to consume either a freeze-dried grape polyphenol powder (GRAPE) or a placebo for 30 d in a double-blind, crossover design, separated by a 3-wk washout period. Participants were asked to maintain their usual diet and physical activity during the study and abstain from consuming polyphenol-rich foods. MetS criteria including blood pressure (BP) and markers of vascular endothelial function including brachial artery flow-mediated vasodilation (FMD), plasma total nitrite + nitrate (NOx) to estimate NO production, plasma soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured at the end of each dietary period. Systolic BP (P < 0.0025) and plasma sICAM-1 concentrations (P < 0.025) were lower, whereas the FMD response was higher (P < 0.0001), during the GRAPE compared with the placebo period. In addition, changes in sVCAM-1 concentrations between periods were positively correlated with changes in systolic BP (r = 0.45; P < 0.05). Although NOx concentrations did not differ between periods, changes in systolic BP were negatively correlated with changes in NOx concentrations (r = -0.44; P < 0.05), indicating the vasodilating properties of NO. Other MetS variables did not differ between the GRAPE and placebo periods. These results suggest that GRAPE polyphenols may potentiate vasorelaxation and reduce BP and circulating cell adhesion molecules, resulting in improvements in vascular function.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Polifenóis/administração & dosagem , Vasodilatação/efeitos dos fármacos , Vitis/química , Adulto , Idoso , Biomarcadores/sangue , Artéria Braquial/efeitos dos fármacos , Artéria Braquial/fisiologia , Estudos Cross-Over , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Liofilização , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Nitratos/sangue , Nitritos/sangue , Placebos , Molécula 1 de Adesão de Célula Vascular/sangue , Vasculite/tratamento farmacológico , Vasodilatação/fisiologiaRESUMO
Atherosclerosis remains the leading cause of death worldwide. Lifestyle modification, including diet and exercise, is recommended to be the primary prevention strategy for atherosclerosis. Dietary patterns have been shown to be strongly associated with atherosclerosis risk. In addition, diet-induced modulation of gut microbiota and the resultant microbial metabolites may influence the progression of atherosclerosis. This review summarizes the role of gut dysbiosis and different microbial metabolites in atherosclerosis, and how different diets may promote or prevent atherosclerosis through gut microbiome modulation. Non-digestible carbohydrates can increase the production of microbial metabolite short-chain fatty acids in the gut, protecting the gut barrier and decreasing overall systemic inflammation. High animal protein/L-carnitine diets may contribute to gut microbiome-dependent production of trimethylamine N-oxide, contributing to atherosclerosis by increased foam cell formation, decreased reverse cholesterol transport (RCT), and pro-thrombotic actions. Western/high-fat diets can increase the gut microbiome production of secondary bile acids and influence downstream signaling via farnesoid X receptor and lead to dysbiosis. Dysbiosis leads to the translocation of lipopolysaccharide (LPS) to the bloodstream by compromising the gut barrier. LPS can activate Toll-like receptor 4 signaling and decrease RCT to exacerbate atherosclerosis. Studies showing a relationship between the gut microbiome and atherosclerosis are still mostly through correlation, while causal pathways are still being uncovered. Future research should integrate proteomics and metabolomics to 16S microbiome sequencing to get a complete picture of the pathways, metabolites, and microbes involved, and to elucidate the complex interaction between the gut microbiome and atherosclerosis.
Assuntos
Aterosclerose , Microbioma Gastrointestinal , Animais , Aterosclerose/etiologia , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Dieta Hiperlipídica , Disbiose , Inflamação , Metabolismo dos Lipídeos , Lipopolissacarídeos/metabolismoRESUMO
In the United States, over three million adults suffer from inflammatory bowel disease (IBD). The gut microbiome, host immune response, and nutrient-microbial interactions are known to play a role in IBD. The relationship between dairy and IBD is controversial; thus, the objectives of this study were to identify how milk polar lipids (MPLs) and anhydrous milk fat affect colitis disease activity, the colonic transcriptome, and the gut microbiome in a mouse model of chemical-induced colitis. Male and female C57BL/6J mice (n = 120) were randomized into either a low (5% w/w) milk fat or a high (21% w/w) milk fat diet supplemented with either 0%, 1%, or 2% w/w of MPLs for three weeks (n = 10/group/sex). Afterwards, colitis was induced using 1% dextran sodium sulfate in drinking water for five days (colitis induction) and then switched to regular water for five days (colitis recovery). Mice fed added MPLs were protected against colitis when fed a high-fat diet, while added MPLs during low-fat diet attenuated disease activity during the colitis induction period yet promoted colitis and inflammation in male mice during the recovery period. Dietary fat content can alter colitis and influence the anti-inflammatory effect of milk polar lipids.
Assuntos
Colite , Doenças Inflamatórias Intestinais , Masculino , Feminino , Camundongos , Animais , Sulfato de Dextrana/efeitos adversos , Gorduras na Dieta/efeitos adversos , Leite , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de DoençasRESUMO
We previously demonstrated that intake of three eggs/d for 4 weeks increased plasma choline and decreased inflammation in subjects with metabolic syndrome (MetS). The purpose of the current study was to further explore the effects of phosphatidylcholine (PC) provided by eggs versus a choline bitartrate (CB) supplement on the gut microbiota, trimethylamine N-oxide (TMAO) formation, and plasma carotenoids lutein and zeaxanthin in MetS. This randomized, controlled crossover clinical trial included 23 subjects with MetS. Following a washout period of 2 weeks without consuming any choline-containing foods, subjects were randomly allocated to consume either three eggs/d or a CB supplement for 4 weeks (both diets had a choline equivalent of 400 mg/day). DNA was extracted from stool samples to sequence the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and the α-diversity of the community were determined using QIIME software. Plasma TMAO, methionine, betaine, and dimethylglycine (DMG) were quantified by stable isotope dilution liquid chromatography with tandem mass spectrometry. Plasma carotenoids, lutein, and zeaxanthin were measured using reversed-phase high-performance liquid chromatography. There were significant increases in plasma lutein and zeaxanthin after egg intake compared to the baseline or intake of CB supplement (p < 0.01). In contrast, TMAO was not different between treatments compared to the baseline (p > 0.05). Additionally, while diet intervention had no effects on microbiota diversity measures or relative taxa abundances, a correlation between bacterial biodiversity and HDL was observed. Following egg intake, the observed increases in plasma lutein and zeaxanthin may suggest additional protection against oxidative stress, a common condition in MetS.
Assuntos
Microbioma Gastrointestinal , Síndrome Metabólica , Carotenoides , Colina , Suplementos Nutricionais , Ovos , Humanos , RNA Ribossômico 16SRESUMO
There is a clear correlation between gut microbiota, diet, and metabolic outcomes. A diet high in fiber has been shown to decrease inflammation, increase insulin sensitivity, and reduce dyslipidemias whereas a diet high in fat and sugar leads to dyslipidemia, insulin resistance, and low-grade inflammation. There is recent evidence suggesting that the human gut microbiota has a significant role in the development or the resolution of metabolic syndrome (MetS) and associated conditions. Leading a stressful, sedentary lifestyle with limited or no physical activity and consuming an unhealthy diet high in saturated fat, simple carbohydrates, and sodium and low in dietary fiber and in high-quality protein are some of the contributing factors. Unhealthy diets have been shown to induce alterations in the gut microbiota and contribute to the pathogenesis of MetS by altering microbiota composition and disrupting the intestinal barrier, which leads to low-grade systemic inflammation. In contrast, healthy diets can lead to changes in microbiota that increase gut barrier function and increase the production of anti-inflammatory biomarkers. This review aims at providing a more in-depth discussion of diet-induced dysbiosis of the gut microbiota and its effect on MetS. Here, we discuss the possible mechanisms involved in the development of the metabolic biomarkers that define MetS, with an emphasis on the role of sugar and dietary fiber in microbiome-mediated changes in low-grade systemic inflammation and metabolic dysfunction.
Assuntos
Microbioma Gastrointestinal , Resistência à Insulina , Síndrome Metabólica , Humanos , Síndrome Metabólica/complicações , Dieta , Fibras na Dieta , Inflamação/complicações , Biomarcadores , Açúcares/farmacologia , Sódio , Dieta HiperlipídicaRESUMO
We recently reported that the inclusion of whole eggs in plant-based diets (PBD) increased plasma choline, lutein, and zeaxanthin in individuals with metabolic syndrome (MetS). The objective of the current study was to evaluate whether this dietary pattern would protect against oxidative stress and low-grade inflammation, two common characteristics of MetS. We recruited 24 men and women with MetS, who, after following a PBD for 2 weeks (baseline), were randomly allocated to consume either two whole eggs with 70 g of spinach/day (EGG) or the equivalent amount of egg substitute with spinach (SUB) as breakfast for 4 weeks. After a 3-week washout, they were allocated to the alternate breakfast. We measured biomarkers of oxidation and inflammation at baseline and at the end of each intervention. Tumor necrosis factor-alpha, interleukin-6, monocyte protein attractant-1, liver enzymes, and C-reactive protein, as well as total antioxidant capacity, paraoxonase-1 (PON-1) activity, and other biomarkers of oxidation were not different at the end of EGG or SUB or when compared to baseline. However, plasma malondialdehyde (MDA) concentrations were lower (p < 0.05) during the EGG and baseline compared to SUB. In addition, the increases in dietary lutein and zeaxanthin previously observed had a strong positive correlation with PON-1 activity (r = 0.522, p < 0.01) only during the EGG period, whereas plasma zeaxanthin was negatively correlated with MDA (r = −0.437, p < 0.01). The number of participants with MetS was reduced from 24 during screening to 21, 13, and 17 during the BL, EGG, and SUB periods, respectively, indicating that eggs were more effective in reversing the characteristics of MetS. These data suggest that adding eggs to a PBD does not detrimentally affect inflammation or oxidative stress; on the contrary, eggs seem to provide additional protection against the biomarkers that define MetS.
Assuntos
Síndrome Metabólica , Biomarcadores , Dieta , Dieta Vegetariana , Ovos/análise , Feminino , Humanos , Inflamação , Luteína , Masculino , Estresse Oxidativo , ZeaxantinasRESUMO
Atherosclerosis develops due to lipid accumulation in the arterial wall and sclerosis as result of increased hyperlipidemia, oxidative stress, lipid oxidation, and protein oxidation. However, improving antioxidant status through diet may prevent the progression of atherosclerotic cardiovascular disease. It is believed that polyphenol-rich plants contribute to the inverse relationship between fruit and vegetable intake and chronic disease. Anthocyanins are flavonoid polyphenols with antioxidant properties that have been associated with reduced risk of cardiovascular disease. The consumption of anthocyanins increases total antioxidant capacity, antioxidant defense enzymes, and HDL antioxidant properties by several measures in preclinical and clinical populations. Anthocyanins appear to impart antioxidant actions via direct antioxidant properties, as well as indirectly via inducing intracellular Nrf2 activation and antioxidant gene expression. These actions counter oxidative stress and inflammatory signaling in cells present in atherosclerotic plaques, including macrophages and endothelial cells. Overall, anthocyanins may protect against atherosclerosis and cardiovascular disease through their effects on cellular antioxidant status, oxidative stress, and inflammation; however, their underlying mechanisms of action appear to be complex and require further elucidation.