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BACKGROUND: Gut microbiota are involved in the onset and development of chronic intestinal inflammation. The recently described endocannabinoidome (eCBome), a diverse and complex system of bioactive lipid mediators, has been reported to play a role in various physio-pathological processes such as inflammation, immune responses and energy metabolism. The eCBome and the gut microbiome (miBIome) are closely linked and form the eCBome - miBIome axis, which may be of special relevance to colitis. METHODS: Colitis was induced in conventionally raised (CR), antibiotic-treated (ABX) and germ-free (GF) mice with dinitrobenzene sulfonic acid (DNBS). Inflammation was assessed by Disease Activity Index (DAI) score, body weight change, colon weight-length ratio, myeloperoxidase (MPO) activity and cytokine gene expression. Colonic eCBome lipid mediator concentrations were measured by HPLC-MS /MS. RESULTS: GF mice showed increased levels of anti-inflammatory eCBome lipids (LEA, OEA, DHEA and 13- HODE-EA) in the healthy state and higher MPO activity. DNBS elicited reduced inflammation in GF mice, having lower colon weight/length ratios and lower expression levels of Il1b, Il6, Tnfa and neutrophil markers compared to one or both of the other DNBS-treated groups. Il10 expression was also lower and the levels of several N-acyl ethanolamines and 13-HODE-EA levels were higher in DNBS-treated GF mice than in CR and ABX mice. The levels of these eCBome lipids negatively correlated with measures of colitis and inflammation. CONCLUSIONS: These results suggest that the depletion of the gut microbiota and subsequent differential development of the gut immune system in GF mice is followed by a compensatory effect on eCBome lipid mediators, which may explain, in part, the observed lower susceptibility of GF mice to develop DNBS-induced colitis.
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Colite , Dinitrobenzenos , Camundongos , Animais , Dinitrobenzenos/efeitos adversos , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Inflamação , LipídeosRESUMO
Background: Gestational diabetes mellitus (GDM) is known to affect human milk composition. Aims of this study were to compare macronutrient and energy content of human milk of women with (GDM+) and without GDM (GDM-), to assess the association between maternal health and human milk macronutrient and energy content and association between human milk macronutrient and energy content and infant growth. Study Design and Methods: Two months after delivery, hindmilk samples were collected. Triglyceride (TG), lactose, and protein content of human milk were measured. An oral glucose tolerance test was performed. Infant weight and length at birth and 2 months were collected. Weight-for-age (WAZ) and weight-for-length z-scores were calculated. Results: Twenty-four GDM+ and 29 GDM- women were included. Protein, lactose, and energy content of human milk were similar between groups. TG concentration was higher in GDM+ than in GDM- women (6.3 ± 2.0 versus 5.3 ± 1.2, p = 0.04). This difference was no longer significant after adjustment for maternal age and infant sex (p = 0.23). Maternal age was associated with TG (r = 0.28, p = 0.04) and lactose (r = -0.30, p = 0.03), while fasting glucose was associated with proteins (r = 0.30, p = 0.03) and tended to be associated with TG (r = 0.27, p = 0.05) and energy (r = 0.24, p = 0.08). TG levels in human milk were associated with weight (ß: 0.26, 95% confidence interval [CI]: 0.02 to 0.50) and WAZ (ß: 0.40, 95% CI: 0.05 to 0.75) at 2 months among children unexposed (GDM-) to GDM, but not among children exposed (GDM+) Conclusions: In conclusion, GDM status, maternal age, and fasting glucose level were associated with human milk composition. Finally, TG in human milk was associated with infant growth among GDM- children but not among GDM+ children. ClinicalTrials.gov NCT02872402.
Assuntos
Diabetes Gestacional , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Aleitamento Materno , Diabetes Gestacional/metabolismo , Glucose , Lactose , Leite Humano/metabolismoRESUMO
Dietary micronutrients act at the intestinal level, thereby influencing microbial communities, the host endocannabinoidome, and immune and anti-oxidative response. Selenium (Se) is a trace element with several health benefits. Indeed, Se plays an important role in the regulation of enzymes with antioxidative and anti-inflammatory activity as well as indicators of the level of oxidative stress, which, together with chronic low-grade inflammation, is associated to obesity. To understand how Se variations affect diet-related metabolic health, we fed female and male mice for 28 days with Se-depleted or Se-enriched diets combined with low- and high-fat/sucrose diets. We quantified the plasma and intestinal endocannabinoidome, profiled the gut microbiota, and measured intestinal gene expression related to the immune and the antioxidant responses in the intestinal microenvironment. Overall, we show that intestinal segment-specific microbiota alterations occur following high-fat or low-fat diets enriched or depleted in Se, concomitantly with modifications of circulating endocannabinoidome mediators and changes in cytokine and antioxidant enzyme expression. Specifically, Se enrichment was associated with increased circulating plasma levels of 2-docosahexaenoyl-glycerol (2-DHG), a mediator with putative beneficial actions on metabolism and inflammation. Others eCBome mediators also responded to the diets. Concomitantly, changes in gut microbiota were observed in Se-enriched diets following a high-fat diet, including an increase in the relative abundance of Peptostreptococcaceae and Lactobacillaceae. With respect to the intestinal immune response and anti-oxidative gene expression, we observed a decrease in the expression of proinflammatory genes Il1ß and Tnfα in high-fat Se-enriched diets in caecum, while in ileum an increase in the expression levels of the antioxidant gene Gpx4 was observed following Se depletion. The sex of the animal influenced the response to the diet of both the gut microbiota and endocannabinoid mediators. These results identify Se as a regulator of the gut microbiome and endocannabinoidome in conjunction with high-fat diet, and might be relevant to the development of new nutritional strategies to improve metabolic health and chronic low-grade inflammation associated to metabolic disorders.
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Microbioma Gastrointestinal , Selênio , Camundongos , Masculino , Feminino , Animais , Microbioma Gastrointestinal/fisiologia , Selênio/farmacologia , Antioxidantes , Dieta Hiperlipídica/efeitos adversos , InflamaçãoRESUMO
The objective of the present study was to test whether a brown seaweed extract rich in polyphenols combined with a low-calorie diet would induce additional weight loss and improve blood glucose homeostasis in association with a metabolic and inflammatory response in overweight/obese prediabetic subjects. Fifty-six overweight/obese, dysglycemic, and insulin-resistant men and women completed a randomized, placebo-controlled, double-blind, and parallel clinical trial. Subjects were administrated 500 mg/d of either brown seaweed extract or placebo combined with individualized nutritional advice for moderate weight loss over a period of 12 weeks. Glycemic, anthropometric, blood pressure, heart rate, body composition, lipid profile, gut integrity, and oxidative and inflammatory markers were measured before and at the end of the trial. No effect was observed on blood glucose. We observed significant but small decreases in plasma C-peptide at 120 min during 2 h-OGTT (3218 ± 181 at pre-intervention vs. 2865 ± 186 pmol/L at post-intervention in the brown seaweed group; 3004 ± 199 at pre-intervention vs. 2954 ± 179 pmol/L at post-intervention in the placebo group; changes between the two groups, p = 0.002), heart rate (72 ± 10 at pre-intervention vs. 69 ± 9 (n/min) at post-intervention in the brown seaweed group; 68 ± 9 at pre-intervention vs. 68 ± 8 (n/min) at post-intervention in the placebo group; changes between the two groups, p = 0.01), and an inhibition in the increase of pro-inflammatory interleukin-6 (IL-6) (1.3 ± 0.7 at pre-intervention vs. 1.5 ± 0.7 pg/L at post-intervention in the brown seaweed group; 1.4 ± 1.1 at pre-intervention vs. 2.2 ± 1.6 pg/L at post-intervention in the placebo group; changes between the two groups, p = 0.02) following brown seaweed consumption compared with placebo in the context of moderate weight loss. Although consumption of brown seaweed extract had no effect on body weight or blood glucose, an early attenuation of the inflammatory response was observed in association with marginal changes in metabolic parameters related to the prevention of diabetes type 2.
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Anti-Inflamatórios/uso terapêutico , Ascophyllum/química , Misturas Complexas/uso terapêutico , Fucus/química , Sobrepeso/tratamento farmacológico , Polifenóis/uso terapêutico , Estado Pré-Diabético/tratamento farmacológico , Alga Marinha/química , Adolescente , Adulto , Idoso , Glicemia/efeitos dos fármacos , Peptídeo C/sangue , Dieta com Restrição de Gorduras , Método Duplo-Cego , Feminino , Humanos , Insulina/sangue , Interleucina-6/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Sobrepeso/sangue , Estado Pré-Diabético/sangue , Resultado do Tratamento , Redução de Peso/efeitos dos fármacos , Adulto JovemRESUMO
The natural inflammation occurring during pregnancy can, under certain conditions, be associated with adverse pregnancy outcomes. This study aimed to (1) quantify changes in circulating concentrations of leptin, adiponectin, interleukin-6 (IL-6) and C-reactive protein (CRP) across trimesters of pregnancy, according to pre-pregnancy body mass index (ppBMI); and (2) examine the trimester-specific associations between the inflammatory markers' concentrations, a Mediterranean diet score (MDS) and the dietary inflammatory index (DII). We measured leptin, adiponectin and IL-6 by ELISA and CRP by high-sensitivity immunonephelometry, in blood samples from 79 pregnant women (age: 32.1 ± 3.7 years; ppBMI: 25.7 ± 5.8 kg/m2). Three Web-based 24-h recalls were completed at each trimester and used to compute the MDS and the DII. CRP concentrations remained stable across trimesters, whereas concentrations of leptin and IL-6 increased, and adiponectin concentrations decreased (p < 0.001). Changes in leptin and adiponectin concentrations also differed according to ppBMI categories (p < 0.05). As for the dietary scores, the only significant association was observed in the second trimester between leptin concentrations and the MDS (r = -0.26, p < 0.05). In conclusion, ppBMI and the progression of pregnancy itself probably supplant the potential associations between diet and the inflammation occurring during that period. Novelty: Circulating leptin and IL-6 concentrations increased across trimesters whereas CRP was stable, and adiponectin decreased. Variations in circulating leptin and adiponectin concentrations differed by ppBMI categories. Very few associations were observed between dietary scores and inflammatory markers.
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Dieta Mediterrânea , Leptina , Adiponectina , Adulto , Biomarcadores , Proteína C-Reativa/metabolismo , Feminino , Humanos , Inflamação , GravidezRESUMO
Vitamin D deficiency is associated with poor mental health and dysmetabolism. Several metabolic abnormalities are associated with psychotic diseases, which can be compounded by atypical antipsychotics that induce weight gain and insulin resistance. These side-effects may be affected by vitamin D levels. The gut microbiota and endocannabinoidome (eCBome) are significant regulators of both metabolism and mental health, but their role in the development of atypical antipsychotic drug metabolic side-effects and their interaction with vitamin D status is unknown. We studied the effects of different combinations of vitamin D levels and atypical antipsychotic drug (olanzapine) exposure on whole-body metabolism and the eCBome-gut microbiota axis in female C57BL/6J mice under a high fat/high sucrose (HFHS) diet in an attempt to identify a link between the latter and the different metabolic outputs induced by the treatments. Olanzapine exerted a protective effect against diet-induced obesity and insulin resistance, largely independent of dietary vitamin D status. These changes were concomitant with olanzapine-mediated decreases in Trpv1 expression and increases in the levels of its agonists, including various N-acylethanolamines and 2-monoacylglycerols, which are consistent with the observed improvement in adiposity and metabolic status. Furthermore, while global gut bacteria community architecture was not altered by olanzapine, we identified changes in the relative abundances of various commensal bacterial families. Taken together, changes of eCBome and gut microbiota families under our experimental conditions might contribute to olanzapine and vitamin D-mediated inhibition of weight gain in mice on a HFHS diet.
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Antipsicóticos/farmacologia , Endocanabinoides/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/tratamento farmacológico , Olanzapina/farmacologia , Vitamina D/farmacologia , Aldo-Ceto Redutases/genética , Aldo-Ceto Redutases/metabolismo , Amidoidrolases/genética , Amidoidrolases/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Sacarose Alimentar/efeitos adversos , Etanolaminas/metabolismo , Feminino , Regulação da Expressão Gênica , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Camundongos , Camundongos Endogâmicos C57BL , Monoacilglicerol Lipases/genética , Monoacilglicerol Lipases/metabolismo , Monoglicerídeos/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/metabolismo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Aumento de Peso/efeitos dos fármacosRESUMO
Monoglyceride lipase (MGLL) regulates metabolism by catabolizing monoacylglycerols (MAGs), including the endocannabinoid 2-arachidonoyl glycerol (2-AG) and some of its bioactive congeners, to the corresponding free fatty acids. Mgll knockout mice (Mgll-/-) exhibit elevated tissue levels of MAGs in association with resistance to the metabolic and cardiovascular perturbations induced by a high fat diet (HFD). The gut microbiome and its metabolic function are disrupted in obesity in a manner modulated by 2-arachidonoyl glycerol (2-AG's) main receptors, the cannabinoid CB1 receptors. We therefore hypothesized that Mgll-/- mice have an altered microbiome, that responds differently to diet-induced obesity from that of wild-type (WT) mice. We subjected mice to HFD and assessed changes in the microbiomes after 8 and 22 weeks. As expected, Mgll-/- mice showed decreased adiposity, improved insulin sensitivity, and altered circulating incretin/adipokine levels in response to HFD. Mgll-/- mice on a chow diet exhibited significantly higher levels of Hydrogenoanaerobacterium, Roseburia, and Ruminococcus than WT mice. The relative abundance of the Lactobacillaceae and Coriobacteriaceae and of the Lactobacillus, Enterorhabdus, Clostridium_XlVa, and Falsiporphyromonas genera was significantly altered by HFD in WT but not Mgll-/- mice. Differently abundant families were also associated with changes in circulating adipokine and incretin levels in HFD-fed mice. Some gut microbiota family alterations could be reproduced by supplementing 2-AG or MAGs in culturomics experiments carried out with WT mouse fecal samples. We suggest that the altered microbiome of Mgll-/- mice contributes to their obesity resistant phenotype, and results in part from increased levels of 2-AG and MAGs.
Assuntos
Dieta Hiperlipídica , Microbioma Gastrointestinal , Monoacilglicerol Lipases/genética , Adipocinas/sangue , Animais , Fezes/microbiologia , Teste de Tolerância a Glucose , Incretinas/sangue , Resistência à Insulina , Lactobacillaceae/genética , Lactobacillaceae/isolamento & purificação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monoacilglicerol Lipases/deficiência , Monoacilglicerol Lipases/metabolismo , Obesidade/microbiologia , Obesidade/patologia , Análise de Componente Principal , Ruminococcus/genética , Ruminococcus/isolamento & purificaçãoRESUMO
Sea cucumbers have been shown to have potential health benefits and are a rich source of several bioactive compounds, particularly triterpenoid saponins. However, most studies concentrate on the body wall, and little is known about the health effects of the coproducts. The objectives of this study were to determine the nutritional composition of a coproduct from the sea cucumber Cucumaria frondosa and the effects of the dietary consumption of this coproduct on cardiometabolic health in rats. Chemical, biochemical, and nutritional analyses were performed to characterize this coproduct. Forty (40) male Wistar rats were then equally divided into four groups and fed a purified control diet or a diet enriched with 0.5%, 1.5%, or 2.5% (by protein) of coproduct. After 28 days of feeding, the rats were sacrificed. Body and tissue weight, body composition, epididymal adipocyte diameter, plasma and hepatic lipids, glycemia, and insulinemia were measured at the end of the 28-day experiment. Analysis of the coproduct revealed high levels of protein, omega-3 fatty acids, minerals, and saponins. The 1.5% group had significantly smaller epididymal adipocytes vs. the control. We conclude that dietary administration of this sea cucumber coproduct at 1.5% doses decreases visceral adiposity, potentially decreasing the risk of cardiometabolic dysfunction. The coproduct's saponin content may contribute to the observed effects, but the impact of other components cannot be ruled out.
Assuntos
Adipócitos/efeitos dos fármacos , Produtos Biológicos/farmacologia , Pepinos-do-Mar/química , Adipócitos/fisiologia , Animais , Produtos Biológicos/química , Composição Corporal/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Pepinos-do-Mar/metabolismoRESUMO
The gut microbiota is a unique ecosystem of microorganisms interacting with the host through several biochemical mechanisms. The endocannabinoidome (eCBome), a complex signaling system including the endocannabinoid system, approximately 50 receptors and metabolic enzymes, and more than 20 lipid mediators with important physiopathologic functions, modulates gastrointestinal tract function and may mediate host cell-microbe communications there. Germ-free (GF) mice, which lack an intestinal microbiome and so differ drastically from conventionally raised (CR) mice, offer a unique opportunity to explore the eCBome in a microbe-free model and in the presence of a reintroduced functional gut microbiome through fecal microbiota transplant (FMT). We aimed to gain direct evidence for a link between the microbiome and eCBome systems by investigating eCBome alterations in the gut in GF mice before and after FMT. Basal eCBome gene expression and lipid profiles were measured in various segments of the intestine of GF and CR mice at juvenile and adult ages using targeted quantitative PCR transcriptomics and LC-MS/MS lipidomics. GF mice exhibited age-dependent modifications in intestinal eCBome gene expression and lipid mediator levels. FMT from CR donor mice to age-matched GF male mice reversed several of these alterations, particularly in the ileum and jejunum, after only 1 week, demonstrating that the gut microbiome directly impacts the host eCBome and providing a cause-effect relationship between the presence or absence of intestinal microbes and eCBome signaling. These results open the way to new studies investigating the mechanisms through which intestinal microorganisms exploit eCBome signaling to exert some of their physiopathologic functions.
Assuntos
Endocanabinoides/metabolismo , Microbioma Gastrointestinal , Intestinos/química , Intestinos/microbiologia , Transdução de Sinais , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Prenatal exposure to persistent organic pollutants (POPs) has been associated with the development of metabolic syndrome-related diseases in offspring. According to epidemiological studies, father's transmission of environmental effects in addition to mother's can influence offspring health. Moreover, maternal prenatal dietary folic acid (FA) may beneficially impact offspring health. The objective is to investigate whether prenatal FA supplementation can overcome the deleterious effects of prenatal exposure to POPs on lipid homeostasis and inflammation in three generations of male rat descendants through the paternal lineage. Female Sprague-Dawley rats (F0) were exposed to a POPs mixture (or corn oil) +/- FA supplementation for 9 weeks before and during gestation. F1 and F2 males were mated with untreated females. Plasma and hepatic lipids were measured in F1, F2, and F3 males after 12-h fast. Gene expression of inflammatory cytokines was determined by qPCR in epididymal adipose tissue. In F1 males, prenatal POPs exposure increased plasma lipids at 14 weeks old and hepatic lipids at 28 weeks old and prenatal FA supplementation decreased plasma total cholesterol at 14 weeks old. Prenatal POPs exposure decreased plasma triglycerides at 14 weeks old in F2 males. No change was observed in inflammatory markers. Our results show an impact of the paternal lineage on lipid homeostasis in rats up to the F2 male generation. FA supplementation of the F0 diet, regardless of POPs exposure, lowered plasma cholesterol in F1 males but failed to attenuate the deleterious effects of prenatal POPs exposure on plasma and hepatic lipids in F1 males.
Assuntos
Suplementos Nutricionais , Poluentes Ambientais/toxicidade , Ácido Fólico/administração & dosagem , Inflamação/patologia , Lipídeos/análise , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/patologia , Animais , Animais Recém-Nascidos , Feminino , Homeostase , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Ratos , Ratos Sprague-DawleyRESUMO
The intestinal microbiota and the expanded endocannabinoid (eCB) system, or endocannabinoidome (eCBome), have both been implicated in diet-induced obesity and dysmetabolism. These systems were recently suggested to interact during the development of obesity. We aimed at identifying the potential interactions between gut microbiota composition and the eCBome during the establishment of diet-induced obesity and metabolic complications. Male mice were fed a high-fat, high-sucrose (HFHS) diet for 56 days to assess jejunum, ileum, and cecum microbiomes by 16S rRNA gene metataxonomics as well as ileum and plasma eCBome by targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). The HFHS diet induced early (3 days) and persistent glucose intolerance followed by weight gain and hyperinsulinemia. Concomitantly, it induced the elevation of the two eCBs, anandamide, in both ileum and plasma, and 2-arachidonoyl-glycerol, in plasma, as well as alterations in several other N-acylethanolamines and 2-acylglycerols. It also promoted segment-specific changes in the relative abundance of several genera in intestinal microbiota, some of which were observed as early as 3 days following HFHS diet. Weight-independent correlations were found between the relative abundances of, among others, Barnesiella, Eubacterium, Adlercreutzia, Parasutterella, Propionibacterium, Enterococcus, and Methylobacterium and the concentrations of anandamide and the anti-inflammatory eCBome mediator N-docosahexaenoyl-ethanolamine. This study highlights for the first time the existence of potential interactions between the eCBome, an endogenous system of multifunctional signaling lipids, and several intestinal genera during early and late HFHS-induced dysmetabolic events, with potential impact on the host capability of adapting to increased intake of fat and sucrose.IMPORTANCE The intestinal microbiota and the expanded endocannabinoid system, or endocannabinoidome, have both been implicated in diet-induced obesity and dysmetabolism. This study aims at identifying the potential interactions between these two fundamental systems-which form the gut microbiota-endocannabinoidome axis-and their involvement in the establishment of diet-induced obesity and related metabolic complications. We report here time- and segment-specific microbiome disturbances as well as modifications of intestinal and circulating endocannabinoidome mediators during high-fat, high-sucrose diet-induced glucose intolerance and subsequent obesity and hyperinsulinemia. This highlights the involvement of, and the interaction between, the gut microbiota and the endocannabinoidome during metabolic adaptation to high-fat and high-sucrose feeding. These results will help identifying actionable gut microbiome members and/or endocannabinoidome mediators to improve metabolic health.
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Cyclic fatty acid monomers (CFAM) generated through domestic or industrial heating of vegetable oils may alter liver enzymes and induce hepatomegaly and steatosis, but the underlying mechanisms are not clearly understood. This study aimed to assess the effects of CFAM on liver and plasma lipids and to determine whether these effects are modulated by dietary lipids. Thirty-six (36) male Wistar rats were fed either of the four isoenergetic diets consisting of canola oil or soybean oil with/without 500 mg/100 g CFAM of total fat for 28 days. Rats fed CFAM had higher liver total lipids (p = 0.03) and triacylglycerols (TAG) (p = 0.02), but less hepatic phosphatidylcholine (p = 0.02) compared to those fed the non-CFAM diets. CFAM did not alter liver phosphatidylethanolamine N-methyltransferase (PEMT) activity and CTP: phosphocholine cytidylyltransferase (CT-α) protein levels. Rats fed CFAM diets had higher levels of plasma total cholesterol (TC), VLDL + LDL cholesterol, higher ratio of TC to HDL cholesterol, and lower levels of HDL cholesterol compared with rats fed non-CFAM diets (p < 0.05). Plasma alanine transaminase (ALT) was decreased with CFAM, but plasma insulin, glucose, and TAG did not vary among the four diet groups (p < 0.05). Rats fed canola oil and CFAM had higher plasma levels of aspartate transaminase (AST) and AST/ALT ratio compared with the other three diet groups. These results indicate that CFAM may provoke an accumulation of TAG in the liver related to a decrease in phosphatidylcholine (PC) levels, but the effect of CFAM on PC concentrations may not occur through impairment of the two main PC biosynthesis pathways.
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This study assesses the effects of cyclic fatty acid monomers (CFAM) from heated vegetable oils on oxidative stress and inflammation. Wistar rats were fed either of these four diets for 28 days: canola oil (CO), canola oil and 0.5% CFAM (CC), soybean oil (SO), and soybean oil and 0.5% CFAM (SC). Markers of oxidative stress and inflammation were determined by micro liquid chromatography tandem mass spectrometry (micro-LC-MS/MS) and enzyme-linked immunosorbent assay (ELISA) kits, respectively. Analysis of variance (ANOVA) for a 2 × 2 factorial design was performed to determine the CFAM and oil effects and interactions between these two factors at P ≤ 0.05. For significant interactions, a post hoc multiple comparison test was performed, i.e., Tukey HSD (honest significant difference) test. CFAM induced higher plasma levels of 15-F2t-IsoP (CC, 396 ± 43 ng/mL, SC, 465 ± 75 ng/mL vs CO, 261 ± 23 ng/mL and SO, 288 ± 35 ng/mL, P < 0.05). Rats fed the SC diet had higher plasma 2,3-dinor-15-F2t-IsoP (SC, 145 ± 9 ng/mL vs CC, 84 ± 8 ng/mL, CO, 12 ± 1 ng/mL, and SO, 12 ± 1 ng/mL, P < 0.05), urinary 2,3-dinor-15-F2t-IsoP (SC, 117 ± 12 ng/mL vs CC, 67 ± 13 ng/mL, CO, 15 ± 2 ng/mL, and SO, 18 ± 4 ng/mL, P < 0.05), and plasma IL-6 (SC, 57 ± 10 pg/mL vs CC, 48 ± 11 pg/mL, CO, 46 ± 9 pg/mL, and SO, 44 ± 4 pg/mL, P < 0.05) than the other three diet groups. These results indicate that CFAM increased the levels of markers of oxidative stress, and those effects are exacerbated by a CFAM-high-linoleic acid diet.
Assuntos
Ácidos Graxos/farmacologia , Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Óleo de Brassica napus/farmacologia , Óleo de Soja/farmacologia , Animais , Biomarcadores/sangue , Biomarcadores/urina , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Ácidos Graxos/sangue , Ácidos Graxos/química , Inflamação/induzido quimicamente , Interleucina-6/sangue , Isoprostanos/metabolismo , Isoprostanos/urina , Ácido Linoleico/efeitos adversos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Neuroprostanos/sangue , Neuroprostanos/urina , Óleo de Brassica napus/efeitos adversos , Ratos Wistar , Óleo de Soja/efeitos adversos , Espectrometria de Massas em TandemRESUMO
This study was designed to determine whether marine-derived proteins other than cod could have beneficial effects on inflammation following muscle injury. Macrophage and neutrophil densities were measured from bupivacaine-injured tibialis anterior muscle of rats fed isoenergetic diets containing either shrimp hydrolysate (Shr), casein hydrolysate (CaH), or whole casein (Ca). In this study, Shr reduced ED1+-macrophages at day 2 (p = 0.013), day 5 (p = 0.006), and day 14 after injury (p = 0.038) compared with Ca, indicating faster resolution of inflammation in Shr. Except for day 2 after injury where Shr led to lower ED1+-macrophages compared with CaH (p = 0.006), both Shr and CaH responded similarly at days 5, 14, and 28 after injury. This findings suggest that beneficial effects of Shr on ED1+-cells might be related to generation of anti-inflammatory peptides through the hydrolysis process, in addition to its high content of anti-inflammatory amino acids. However, while increasing myofiber cross-sectional area in noninjured muscles compared with both Ca and CaH, Shr failed to have a positive effect in corresponding injured muscles. These data indicate that shrimp hydrolysate can facilitate resolution of inflammation after muscle injury mainly through modulating proinflammatory macrophage accumulation but have less effect on optimal recovery in terms of muscle mass and fiber size.
Assuntos
Inflamação/tratamento farmacológico , Músculo Esquelético/efeitos dos fármacos , Hidrolisados de Proteína/administração & dosagem , Ferimentos e Lesões/tratamento farmacológico , Animais , Bupivacaína/toxicidade , Caseínas/administração & dosagem , Inflamação/fisiopatologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Músculo Esquelético/lesões , Músculo Esquelético/fisiopatologia , Pandalidae/química , Hidrolisados de Proteína/química , Ratos , Ferimentos e Lesões/induzido quimicamente , Ferimentos e Lesões/fisiopatologiaRESUMO
Cyclic fatty acid monomers (CFAM) are mainly formed during heat treatments, such as frying, of edible oils. These fatty acids are mixtures of disubstituted five- or six-carbon-membered ring structures. Some earlier studies have suggested that some of these molecules could be metabolized and detoxified, but so far, neither the detoxification mechanisms nor the metabolite identifications have been elucidated. The objective of the present study was to identify the metabolites resulting from the metabolism and detoxification of CFAM. A deuterium-labeled CFAM, [9-(2)H]-10-(6-propyl-2-cyclohexenyl)-dodecenoic acid, was synthesized and fed to rats for 3 days, along with a standard chow diet while the control group was fed the same chow diet which did not contain any CFAM. Biological fluids (urine, blood) were collected for both groups of rats and analyzed using an untargeted metabolomic approach by ultra-performance liquid chromatography coupled with mass spectrometry. Two discriminant metabolites and 18 molecules derived from CFAM were identified or tentatively identified in plasma and urine samples, respectively. The structures of the metabolites suggest that CFAM having a six-carbon-membered ring could be detoxified by the classical drug metabolic pathway (phase I and phase II reactions), but our study also indicates that these are substrates for the ß-oxidation pathway and eliminated as glucuronide, sulphate, and/or nitrate conjugates. Urine metabolomics investigations without diet effects have indicated a higher excretion of medium-chain acylcarnitines in the D-CFAM diet group, which may indicate an incomplete ß-oxidation.
Assuntos
Gorduras Insaturadas na Dieta/metabolismo , Ácidos Graxos/metabolismo , Animais , Culinária , Ciclização , Gorduras Insaturadas na Dieta/análise , Gorduras Insaturadas na Dieta/sangue , Gorduras Insaturadas na Dieta/urina , Ácidos Graxos/análise , Ácidos Graxos/sangue , Ácidos Graxos/urina , Temperatura Alta , Masculino , Espectrometria de Massas , Redes e Vias Metabólicas , Metabolômica , Oxirredução , Ratos , Ratos Sprague-DawleyRESUMO
We have shown that feeding cod protein, which is rich in anti-inflammatory arginine, glycine, and taurine, may beneficially modulate the inflammatory response during recovery following skeletal muscle injury; however it is unknown if these amino acids are responsible for this effect. This study was designed to assess whether supplementing casein with an amino acid mixture composed of arginine, glycine, taurine and lysine, matching their respective levels in cod protein, may account for the anti-inflammatory effect of cod protein. Male Wistar rats were fed isoenergetic diets containing either casein, cod protein, or casein supplemented with L-arginine (0.45%), glycine (0.43%), L-taurine (0.17%) and L-lysine (0.44%) (casein+). After 21 days of ad libitum feeding, one tibialis anterior muscle was injured with 200 µl bupivacaine while the saline-injected contra-lateral tibialis anterior was served as sham. Cod protein and casein+ similarly modulated the inflammation as they decreased COX-2 level at day 2 post-injury (cod protein, p=0.014; casein+, p=0.029) and ED1(+) macrophage density at days 2 (cod protein, p=0.012; casein+, p<0.0001), 5 (cod protein, p=0.001; casein+, p<0.0001) and 14 (cod protein, p<0.0001; casein+, p<0.0001) post-injury, and increased ED2(+) macrophage density at days 5 (cod protein, p<0.0001; casein+, p=0.006), 14 (cod protein, p=0.001; casein+, p<0.002) and 28 (cod protein, p<0.009; casein+, p<0.005) post-injury compared with casein. Furthermore, cod protein up-regulated (p=0.037) whereas casein+ tended to up-regulate (p=0.062) myogenin expression at day 5 post-injury compared with casein. In the cod protein-fed group, these changes resulted in greater muscle mass at days 14 (p=0.002), and 28 (p=0.001) post-injury and larger myofiber cross-sectional area at day 28 post-injury compared with casein (p=0.012). No such effects were observed with casein+. These data indicate that anti-inflammatory actions of cod protein, contrary to its effect on muscle mass recovery, are driven by its high levels of arginine, glycine, taurine and lysine.
Assuntos
Aminoácidos/metabolismo , Proteínas de Peixes/administração & dosagem , Gadiformes , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Animais , Arginina/metabolismo , Ciclo-Oxigenase 2/metabolismo , Proteínas Alimentares/administração & dosagem , Proteínas Alimentares/química , Ingestão de Alimentos , Proteínas de Peixes/química , Glicina/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Lisina/metabolismo , Masculino , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/lesões , Proteína MyoD/metabolismo , Miogenina/metabolismo , Tamanho do Órgão , Ratos , Taurina/metabolismo , Aumento de PesoRESUMO
This study examined the effect of peanut and cod proteins on post-damage skeletal muscle repair, compared with casein. We hypothesized that because of their high arginine content, these proteins would improve the resolution of inflammation and muscle mass recovery following injury. One hundred and twenty-eight male Wistar rats were assigned to isoenergetic diets composed of casein and peanut (experiment 1) or cod protein (experiment 2). After 21 days of feeding, one tibialis anterior muscle (TA) was injured with bupivacaine, while the contralateral TA was injected with saline (sham muscle). Measurements were taken at days 0, 3, 14, and 24 post-injury. Compared with casein, peanut protein reduced muscle mass at days 0 (-12%, p = 0.005) and 14 post-injury in the injured muscle (-13%, p = 0.04), and lowered myofiber cross-sectional area in both the sham (-21%, p = 0.008) and injured muscles (-26%, p = 0.05) at day 24 post-injury, showing that peanut protein has a weak potential to support muscle growth. At day 14 post-injury, muscle mass in the sham (13%, p = 0.02) and injured muscles (12%, p = 0.01) was higher in cod-protein-fed rats, indicating better muscle mass recovery, than in casein-fed rats. Cod protein tended (p = 0.06) to decrease the density of neutrophils (-24%) at day 14 post-injury in the injured muscle, and to decrease the density of ED1(+) macrophages at day 24 post-injury in both sham (-29%, p = 0.03) and injured (-40%, p = 0.01) muscles. No effects were observed for peanut protein. These data indicate that cod protein is better for promoting growth and regeneration of skeletal muscle after trauma, partly because of the improved resolution of inflammation.
Assuntos
Proteínas de Peixes/farmacologia , Gadiformes/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/lesões , Regeneração/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Arachis/metabolismo , Caseínas/farmacologia , Dieta/métodos , Modelos Animais de Doenças , Proteínas de Peixes/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Músculo Esquelético/metabolismo , Ratos , Ratos Wistar , Cloreto de SódioRESUMO
The facial expression of pain plays a crucial role in pain communication and pain diagnostics. Despite its importance, it has remained unknown which dimensions of pain (sensory and/or affective) are encoded in the face. To answer this question, we used a well-established cognitive strategy (suggestions) to differentially modulate the sensory and affective dimensions of pain and investigate the effect of this manipulation on facial responses to experimental pain. Twenty-two subjects participated in the study. Their facial expressions, pain intensity, and unpleasantness ratings as well as skin conductance responses to tonic and phasic heat pain were assessed before and after suggestions directed toward increase in affective and sensory qualities of pain, respectively, were provided. Facial expressions were analyzed with the Facial Action Coding system. As expected, suggestions designed to increase the sensory dimension produced a selective increase in pain intensity ratings, whereas suggestions designed to increase pain affect produced increased unpleasantness ratings and elevated skin conductance responses. Furthermore, suggestions for either increased pain affect or pain sensation produced selective modulations in facial response patterns, with facial movements around the eyes mostly encoding sensory aspects, whereas movements of the eyebrows and of the upper lip were closely associated with the affective pain dimension. The facial expression of pain is a multidimensional response system that differentially encodes affective and sensory pain qualities. This differential encoding might have evolved to guarantee that the specific characteristics of one's pain experience are facially communicated, thereby ensuring adequate help and support from others.
Assuntos
Afeto/fisiologia , Emoções Manifestas/fisiologia , Expressão Facial , Dor/psicologia , Sensação/fisiologia , Estresse Psicológico/psicologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Dor/diagnóstico , Dor/fisiopatologia , Estresse Psicológico/diagnóstico , Estresse Psicológico/fisiopatologia , Adulto JovemRESUMO
It is well known that diets high in nuts or peanuts favourably affect plasma lipid concentrations. However, few studies have examined the effects of nut and peanut protein (PP) on body composition and skeletal muscle properties. The present study was aimed at evaluating the effect of dietary PP compared with two animal proteins, casein (C) and cod protein (CP) on body composition, skeletal muscle contractile properties and lipid metabolism in rats. Thirty-two male rats were assigned to one of the following four diets containing either C, CP, PP or C+peanut protein (CPP, 50:50) mixture. After 28 d of ad libitum feeding and after 12-h fast, blood, liver and muscle were collected for measurements of plasma and hepatic cholesterol and TAG, plasma glucose and insulin and contractile properties. Rats fed with the low-quality protein, PP, had lower body weight gain, body protein mass, soleus mass and liver weight than those fed with the high-quality dietary proteins, C and CP. PP also caused a deficit in contractile properties in soleus. Likewise, PP increased plasma cholesterol and body fat mass compared with CP. However, these elevations were accompanied with increased hepatic TAG concentrations and lowered intestinal fat excretion. These results show that PP intake alters body composition by reducing skeletal muscle mass and liver weight as well as muscle contractility and lipid metabolism. Adding a complete protein such as C might partially counteract these adverse effects.
Assuntos
Arachis/química , Composição Corporal/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Proteínas de Plantas/farmacologia , Animais , Glicemia/efeitos dos fármacos , Dieta , Proteínas Alimentares/análise , Proteínas Alimentares/farmacologia , Ingestão de Alimentos , Insulina/sangue , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Músculo Esquelético , Tamanho do Órgão , Proteínas de Plantas/química , Ratos , Ratos WistarRESUMO
The objective of the present study was to compare the effects of cis-9,trans-11 + trans-8,cis-10 conjugated linoleic acid (CLA) mixture to those of cis-9,trans-11 + trans-10,cis-12 CLA mixture and linoleic acid (LA) on lipoprotein profile, hepatic lipids, body composition and digestibility of dietary fat in hamsters (n = 17) fed diets containing 2% of experimental fat (w/w) for 28 days. The cis-9,trans-11 + trans-10,cis-12 CLA mixture showed higher LDL cholesterol concentrations than LA and the cis-9,trans-11 + trans-8,cis-10 CLA mixture. The cis-9,trans-11 + trans-8,cis-10 CLA mixture induced similar plasma LDL cholesterol and hepatic lipid concentrations, and coefficient of digestibility as LA, indicating no effect of the trans-8,cis-10 CLA isomer on these lipid parameters. On the other hand, the cis-9,trans-11 + trans-8,cis-10 CLA mixture induced higher plasma VLDL cholesterol and triglycerides than LA and the cis-9,trans-11 + trans-10,cis-12 CLA mixture. The cis-9,trans-11 + trans-8,cis-10 CLA mixture also induced the highest plasma glucose concentrations compared with the two other groups, indicating an impairment of glycemic control. No differences in body composition were noted between the three groups. The present results thus show that the cis-9,trans-11 + trans-8,cis-10 CLA mixture can deteriorate plasma VLDL cholesterol and triglycerides in hamsters, possibly due to an increased flux of glucose.