RESUMO
Capsaicin, a pungent compound in chili peppers, is described as having potent anti-inflammatory, antioxidant, and antimicrobial properties. It is also described as a potential modulator of the immune system and intestinal microbiota. Oral or rectal administration of capsaicin has been studied to treat or prevent colitis. However, those vias are often not well accepted due to the burning sensation that capsaicin can cause. Our objective was to evaluate whether the application of capsaicin skin creams (0.075%) would be effective in improving inflammation and epithelial barrier function as well as the composition of the gut microbiota in a model of mild colitis induced by dextran sulfate sodium (1.5%). The results showed that the cutaneous application of capsaicin reversed weight loss and decreased colon shortening and diarrhea, all typical signs of colitis. There was also an improvement in the intestinal epithelial barrier, preserving proteins from tight junctions. We also evaluated the biodistribution of 99mtechnetium-radiolabeled capsaicin (99mTc-CAPS) applied to the back skin of the animals. We found significant concentrations of 99 mTc-Cap in the colon and small intestine after 2 and 4 h of administration. In addition, there was an increased expression of capsaicin receptor TRPV1 in the colon. Moreover, animals with colitis receiving cutaneous capsaicin presented a better short-chain fatty acid profile and increased levels of SIgA, suggesting increased microbiota diversity. In conclusion, our work opens avenues for further studies to better understand capsaicin's potential benefits and mechanisms in addressing colitis through cutaneous application.
RESUMO
Hypercholesterolemia is one of the most important risk factors for cardiovascular diseases. However, it is mostly associated with vascular dysfunction and atherosclerotic lesions, while evidence of direct effects of hypercholesterolemia on cardiomyocytes and heart function is still incomplete and controversial. In this study, we assessed the direct effects of hypercholesterolemia on heart function and the electro-contractile properties of isolated cardiomyocytes. After 5 weeks, male Swiss mice fed with AIN-93 diet added with 1.25% cholesterol (CHO), developed an increase in total serum cholesterol levels and cardiomyocytes cholesterol content. These changes led to altered electrocardiographic records, with a shortening of the QT interval. Isolated cardiomyocytes displayed a shortening of the action potential duration with increased rate of depolarization, which was explained by increased IK, reduced ICa.L and altered INa voltage-dependent inactivation. Also, reduced diastolic [Ca2+]i was found with preserved adrenergic response and cellular contraction function. However, contraction of isolated hearts is impaired in isolated CHO hearts, before and after ischemia/reperfusion, although CHO heart was less susceptible to arrhythmic contractions. Overall, our results demonstrate that early hypercholesterolemia-driven increase in cellular cholesterol content is associated with direct modulation of the heart and cardiomyocytes' excitability, Ca2+ handling, and contraction.
Assuntos
Hipercolesterolemia , Miócitos Cardíacos , Animais , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Hipercolesterolemia/fisiopatologia , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Camundongos , MasculinoRESUMO
Mucositis is a high-incidence side effect in cancer patients undergoing chemotherapy. Next-generation probiotics are emerging as new therapeutic tools for managing various disorders. Studies have demonstrated the potential of Akkermansia muciniphila to increase the efficiency of anticancer treatment and to mitigate mucositis. Due to the beneficial effect of A. muciniphila on the host, we evaluated the dose-response, the microorganism viability, and the treatment protocol of A. muciniphila BAA-835 in a murine model of chemotherapy-induced mucositis. Female Balb/c mice were divided into groups that received either sterile 0.9% saline or A. muciniphila by gavage. Mucositis was induced using a single intraperitoneal injection of 5-fluorouracil. The animals were euthanized three days after the induction of mucositis, and tissue and blood were collected for analysis. Prevention of weight loss and small intestine shortening and reduction of neutrophil and eosinophil influx were observed when animals were pretreated with viable A. muciniphila at 1010 colony-forming units per mL (CFU/mL). The A. muciniphila improved mucosal damage by preserving tissue architecture and increasing villus height and goblet cell number. It also improved the integrity of the epithelial barrier, decreasing intestinal permeability and bacterial translocation. In addition, the treatment prevented the expansion of Enterobacteriaceae. The immunological parameters were also improved by decreasing the expression of pro-inflammatory cytokines (IL6, IL1ß, and TNF) and increasing IL10. In conclusion, pretreatment with 1010 CFU/mL of viable A. muciniphila effectively controlled inflammation, protected the intestinal mucosa and the epithelial barrier, and prevented Enterobacteriaceae expansion in treated mice.
Assuntos
Antineoplásicos , Mucosite , Humanos , Camundongos , Feminino , Animais , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/metabolismo , Citocinas/metabolismo , Mucosa Intestinal/metabolismo , Antineoplásicos/farmacologia , AkkermansiaRESUMO
Although it is well established that platelet-activated receptor (PAF) and protease-activated receptor 2 (PAR2) play a pivotal role in the pathophysiology of lung and airway inflammatory diseases, a role for a PAR2-PAFR cooperation in lung inflammation has not been investigated. Here, we investigated the role of PAR2 in PAF-induced lung inflammation and neutrophil recruitment in lungs of BALB/c mice. Mice were pretreated with the PAR2 antagonist ENMD1068, PAF receptor (PAFR) antagonist WEB2086, or aprotinin prior to intranasal instillation of carbamyl-PAF (C-PAF) or the PAR2 agonist peptide SLIGRL-NH2 (PAR2-AP). Leukocyte infiltration in bronchoalveolar lavage fluid (BALF), C-X-C motif ligand 1 (CXCL)1 and CXCL2 chemokines, myeloperoxidase (MPO), and N-acetyl-glycosaminidase (NAG) levels in BALF, or lung inflammation were evaluated. Intracellular calcium signaling, PAFR/PAR2 physical interaction, and the expression of PAR2 and nuclear factor-kappa B (NF-ÐB, p65) transcription factor were investigated in RAW 264.7 cells stimulated with C-PAF in the presence or absence of ENMD1068. C-PAF- or PAR2-AP-induced neutrophil recruitment into lungs was inhibited in mice pretreated with ENMD1068 and aprotinin or WEB2086, respectively. PAR2 blockade impaired C-PAF-induced neutrophil rolling and adhesion, lung inflammation, and production of MPO, NAG, CXCL1, and CXCL2 production in lungs of mice. PAFR activation reduced PAR2 expression and physical interaction of PAR2 and PAFR; co-activation is required for PAFR/PAR2 physical interaction. PAR2 blockade impaired C-PAF-induced calcium signal and NF-κB p65 translocation in RAW 264.7 murine macrophages. This study provides the first evidence for a cooperation between PAFR and PAR2 mediating neutrophil recruitment, lung inflammation, and macrophage activation.
Assuntos
NF-kappa B , Pneumonia , Camundongos , Animais , NF-kappa B/metabolismo , Fator de Ativação de Plaquetas/metabolismo , Receptor PAR-2/genética , Receptor PAR-2/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Aprotinina/metabolismo , Infiltração de Neutrófilos , Ativação Transcricional , Pneumonia/induzido quimicamenteRESUMO
Capsaicin, a lipophilic, volatile compound, is responsible for the pungent properties of chili peppers. In recent years, a significant increase in investigations into its properties has allowed the production of new formulations and the development of tools with biotechnological, diagnostic, and potential therapeutic applications. Most of these studies show beneficial effects, improving antioxidant and anti-inflammatory status, inducing thermogenesis, and reducing white adipose tissue. Other mechanisms, including reducing food intake and improving intestinal dysbiosis, are also described. In this way, the possible clinical application of such compound is expanding every year. This opinion article aims to provide a synthesis of recent findings regarding the mechanisms by which capsaicin participates in the control of non-communicable diseases such as obesity, diabetes, and dyslipidemia.
Assuntos
Capsicum , Neuralgia , Capsaicina/uso terapêutico , Capsaicina/farmacologia , Neuralgia/tratamento farmacológico , Obesidade/tratamento farmacológicoRESUMO
Obesity is closely associated with non-alcoholic fatty liver disease (NAFLD), characterized by hepatic fat accumulation and hepatocyte injury. Preclinical studies have shown exacerbated weight gain associated with an obesogenic gluten-containing diet. However, whether gluten affects obesity-induced hepatic lipid accumulation still remains unclear. We hypothesized that gluten intake could affect fatty liver development in high-fat diet (HFD)-induced obese mice. Thus, we aimed to investigate the impact of gluten intake on NAFLD in HFD-induced obese mice. Male apolipoprotein E-deficient (Apoe-/-) mice were fed with a HFD containing (GD) or not (GFD) vital wheat gluten (4.5%) for 10 weeks. Blood and liver were collected for further analysis. We found that gluten exacerbated weight gain, hepatic fat deposition, and hyperglycemia without affecting the serum lipid profile. Livers of the GD group showed a larger area of fibrosis, associated with the expression of collagen and MMP9, and higher expression of apoptosis-related factors, p53, p21, and caspase-3. The expression of lipogenic factors, such as PPARγ and Acc1, was more elevated and factors related to beta-oxidation, such as PPARα and Cpt1, were lower in the GD group compared to the GFD. Further, gluten intake induced a more significant expression of Cd36, suggesting higher uptake of free fatty acids. Finally, we found lower protein expression of PGC1α followed by lower activation of AMPK. Our data show that gluten-containing high-fat diet exacerbated NAFLD by affecting lipogenesis and fatty acid oxidation in obese Apoe-/- mice through a mechanism involving lower activation of AMPK.
RESUMO
This cross-sectional study evaluated the association between human exposure to mercury and cardiovascular risk using lipid profile (including apolipoproteins) and genetic analysis of Amazonian riverine population. Anthropometric data (gender, age, height, weight, blood pressure, and neck and waist circumferences) of the participants were recorded. Total mercury and methylmercury (MeHg) content were quantified in hair by ICP-MS and GC-pyro-AFS system. Polymorphisms rs662799, rs693, rs429358 and rs7412 (of genes of apolipoproteins A-V, B, and E at positions 112 and 158, respectively) were genotyped by real-time PCR. The population presented a dyslipidemia profile significantly correlated with high mercury levels. The apolipoprotein B/apolipoprotein A-I (ApoB/ApoA-I) index was also positively correlated with mercury, supporting a possible causal relationship. Allelic distributions were similar to those described in other populations, suggesting that genetic susceptibility may not have a significant role in the lipid alterations found in this work. This study demonstrated for the first time: i) the relationship between mercury exposure and cardiovascular risk-related apolipoproteins in humans, ii) the ApoB levels and the ApoB/ApoA-I index as the risk factors more strongly associated to the mercury-related dyslipidemia in humans, and iii) the prevalence of high/moderate risk of acute myocardial infarction in the vulnerable and chronically exposed-populations of the Amazon, in addition to the genotypic profile of the three most frequent polymorphisms in apolipoproteins of relevance for cardiovascular risk. This early detection of lipid alterations is essential to prevent the development of cardiovascular diseases (CVD), especially in chronically exposed populations such as those found in the Amazon. Therefore, in addition to provide data for the Minamata Convention implementation, our work is in line with the efforts joined by all members of the World Health Organization committed to reducing premature deaths originating from non-communicable diseases by 25% in 2025, including CVD.
Assuntos
Doenças Cardiovasculares , Dislipidemias , Mercúrio , Humanos , Estudos Transversais , Apolipoproteína A-I/genética , Apolipoproteína A-I/análise , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Fatores de Risco , Populações Vulneráveis , Mercúrio/toxicidade , Mercúrio/análise , Apolipoproteínas B/análise , Apolipoproteínas/análise , Fatores de Risco de Doenças Cardíacas , Dislipidemias/induzido quimicamente , Dislipidemias/epidemiologia , Dislipidemias/genética , Cabelo/químicaRESUMO
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder in the world. We have seen that gluten intake exacerbated obesity and atherosclerosis in apolipoprotein E knockout (ApoE-/-) mice. In this study, we investigated the effect of gluten consumption on inflammation and oxidative stress in the liver of mice with NAFLD. Male ApoE-/- mice were fed a gluten-free (GF-HFD) or gluten-containing (G-HFD) high-fat diet for 10 weeks. Blood, liver, and spleen were collected to perform the analyses. The animals of the gluten group had increased hepatic steatosis, followed by increased serum AST and ALT. Gluten intake increased hepatic infiltration of neutrophils, macrophages, and eosinophils, as well as the levels of chemotaxis-related factors CCL2, Cxcl2, and Cxcr3. The production of the TNF, IL-1ß, IFNγ, and IL-4 cytokines in the liver was also increased by gluten intake. Furthermore, gluten exacerbated the hepatic lipid peroxidation and nitrotyrosine deposition, which were associated with increased production of ROS and nitric oxide. These effects were related to increased expression of NADPH oxidase and iNOS, as well as decreased activity of superoxide dismutase and catalase enzymes. There was an increased hepatic expression of the NF-κB and AP1 transcription factors, corroborating the worsening effect of gluten on inflammation and oxidative stress. Finally, we found an increased frequency of CD4+FOXP3+ lymphocytes in the spleen and increased gene expression of Foxp3 in the livers of the G-HFD group. In conclusion, dietary gluten aggravates NAFLD, exacerbating hepatic inflammation and oxidative stress in obese ApoE-deficient mice.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Masculino , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Dieta Hiperlipídica/efeitos adversos , Glutens/metabolismo , Camundongos Knockout para ApoE , Fígado/metabolismo , Inflamação/metabolismo , Estresse Oxidativo , Apolipoproteínas E/genética , Fatores de Transcrição Forkhead/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Methylmercury (MeHg) is highly toxic to the human brain. Although much is known about MeHg neurotoxic effects, less is known about how chronic MeHg affects hippocampal amino acids and other neurochemical markers in adult mice. In this study, we evaluated the MeHg effects on systemic lipids and inflammation, hippocampal oxidative stress, amino acid levels, neuroinflammation, and behavior in adult male mice. Challenged mice received MeHg in drinking water (2 mg/L) for 30 days. We assessed weight gain, total plasma cholesterol (TC), triglycerides (TG), endotoxin, and TNF levels. Hippocampal myeloperoxidase (MPO), malondialdehyde (MDA), acetylcholinesterase (AChE), amino acid levels, and cytokine transcripts were evaluated. Mice underwent open field, object recognition, Y, and Barnes maze tests. MeHg-intoxicated mice had higher weight gain and increased the TG and TC plasma levels. Elevated circulating TNF and LPS confirmed systemic inflammation. Higher levels of MPO and MDA and a reduction in IL-4 transcripts were found in the hippocampus. MeHg-intoxication led to increased GABA and glycine, reduced hippocampal taurine levels, delayed acquisition in the Barnes maze, and poor locomotor activity. No significant changes were found in AChE activity and object recognition. Altogether, our findings highlight chronic MeHg-induced effects that may have long-term mental health consequences in prolonged exposed human populations.
Assuntos
Compostos de Metilmercúrio , Animais , Humanos , Masculino , Camundongos , Acetilcolinesterase/metabolismo , Aminoácidos , Hipocampo/metabolismo , Inflamação/induzido quimicamente , Compostos de Metilmercúrio/toxicidade , Compostos de Metilmercúrio/metabolismo , Aumento de Peso , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Epidemiological and experimental studies have shown a protective effect of helminth infections in weight gain and against the development of metabolic dysfunctions in the host. However, the mechanisms Treg cells exert in the helminth-obesity interface has been poorly investigated. The present study aimed to verify the influence of Heligmosomoides polygyrus infection in early stages of high fat diet-induced obesity. PRINCIPAL FINDINGS: The presence of infection was able to prevent exacerbated weight gain in mice fed with high fat diet when compared to non-infected controls. In addition, infected animals displayed improved insulin sensitivity and decreased fat accumulation in the liver. Obesity-associated inflammation was reduced in the presence of infection, demonstrated by lower levels of leptin and resistin, lower infiltration of Th1 and Th17 cells in adipose tissue, higher expression of IL10 and adiponectin, increased infiltration of Th2 and eosinophils in adipose tissue of infected animals. Of note, the parasite infection was associated with increased Treg frequency in adipose tissue which showed higher expression of cell surface markers of function and activation, like LAP and CD134. The infection could also increase adipose Treg suppressor function in animals on high fat diet. CONCLUSION: These data suggest that H. polygyrus modulates adipose tissue Treg cells with implication for weight gain and metabolic syndrome.
Assuntos
Dieta Hiperlipídica , Resistência à Insulina , Tecido Adiposo , Animais , Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Aumento de PesoRESUMO
Intestinal mucositis (IM) is a critical side-effect associated with antineoplastic therapy. Treatment available is only palliative and often not effective. However, alternative therapeutic strategies, such as probiotics, have attracted significant attention due to their immune-modulatory action in several diseases. Thus, the present study aims to elucidate the therapeutic potential of the probiotic strain Bifidobacterium longum 51A in a murine model of mucositis induced by irinotecan. Due to the scarcity of studies on dose-response and viability (probiotic vs paraprobiotic), we first evaluated which dose and cell viability would be most effective in treating mucositis. In this study, the oral pretreatment with viable B. longum 51A at a concentration of 1 × 109 CFU/mL reduced the daily disease activity index (p < 0.01), protected the intestinal architecture, preserved the length of the intestine (p < 0.05), and reduced intestinal permeability (p < 0.01), inflammation, and oxidative damage (p < 0.01) induced by irinotecan. Also, treatment with B. longum 51A increased the production of secretory immunoglobulin A (p < 0.05) in the intestinal fluid of mice with mucositis. Furthermore, B. longum 51A reversed the mucositis-induced increase in Enterobacteriaceae bacterial group in the gut (p < 0.01). In conclusion, these results showed that oral administration of B. longum 51A protects mice against intestinal damage caused by irinotecan, suggesting its use as a potential probiotic in therapy during mucositis.
Assuntos
Bifidobacterium longum , Microbioma Gastrointestinal/efeitos dos fármacos , Enteropatias , Irinotecano/efeitos adversos , Mucosite , Probióticos/farmacologia , Animais , Feminino , Enteropatias/induzido quimicamente , Enteropatias/microbiologia , Enteropatias/terapia , Irinotecano/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Mucosite/induzido quimicamente , Mucosite/microbiologia , Mucosite/terapiaRESUMO
Apolipoprotein E plays a crucial role in cholesterol metabolism. The immunomodulatory functions of the human polymorphic APOE gene have gained particular interest because APOE4, a well-recognized risk factor for late-onset Alzheimer's disease, has also been recently linked to increased risk of COVID-19 infection severity in a large UK biobank study. Although much is known about apoE functions in the nervous system, much less is known about APOE polymorphism effects on malnutrition and enteric infections and the consequences for later development in underprivileged environments. In this review, recent findings are summarized of apoE's effects on intestinal function in health and disease and the role of APOE4 in protecting against infection and malnutrition in children living in unfavorable settings, where poor sanitation and hygiene prevail, is highlighted. The potential impact of APOE4 on later development also is discussed and gaps in knowledge are identified that need to be addressed to protect children's development under adverse environments.
Assuntos
Apolipoproteína E4 , Doença Crônica , Desnutrição , Doença de Alzheimer , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Apolipoproteínas E/genética , Criança , Humanos , Desnutrição/complicaçõesRESUMO
Mercury (Hg) is one of the most toxic environmental pollutants, especially when methylated, forming methylmercury (MeHg). MeHg affects DNA repair, increases oxidative stress, and predisposes to cancer. MeHg neurotoxicity is well-known, but recently MeHg-associated cardiovascular effects were recognized. This study evaluated circulating lipids, oxidative stress, and genotoxicity after MeHg-chronic exposure (20 mg/L in drinking water) in C57BL/6J wild-type and APOE knockout (ko) mice, the latter, being spontaneously dyslipidemic. Experimental mice were assigned to four groups: non-intoxicated and MeHg-intoxicated wild-type mice and non-intoxicated and MeHg-intoxicated APOE ko mice. Plasma levels of triglycerides, total cholesterol (TC), HDL, and LDL were analyzed. Liver lipid peroxidation and splenic gene expression of xeroderma pigmentosum complementation groups A, C, D, and G (XPA, XPC, XPD, and XPG), X-ray repair cross-complementing protein 1 (XRCC1), and telomerase reverse transcriptase (TERT) were measured. Fur Hg levels confirmed chronic MeHg intoxication. MeHg exposure raises TC levels both in wild-type and APOE ko mice. HDL and LDL-cholesterol levels were increased only in the MeHg-challenged APOE ko mice. MeHg increased liver lipid peroxidation, regardless of the genetic background. Unintoxicated APOE ko mice showed higher expression of TERT than all other groups. APOE deficiency increases XPA expression, regardless of MeHg intoxication. Furthermore, MeHg-intoxicated mice had more cytogenetic abnormalities, effect which was independent of APOE deficiency. More studies are needed to dissect the interactions between circulating lipids, MeHg intoxication, and DNA-repair pathways even at young age, interactions that likely play critical roles in cell senescence and the risk for chronic disorders later in life.
Assuntos
Aberrações Cromossômicas/induzido quimicamente , Reparo do DNA/efeitos dos fármacos , Compostos de Metilmercúrio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/metabolismo , Dislipidemias/metabolismo , Poluentes Ambientais/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoERESUMO
The metabolic syndrome (MetS) epidemic is a global challenge. Although developing countries (including Brazil, India, and South Africa) present a higher proportion of deaths by cardiovascular diseases than developed countries, most of our knowledge is from these developed countries. Amazonian riverine populations (ARP), as well as other vulnerable populations of the Southern Hemisphere, share low-income and traditional practices, among other features. This large cross-sectional study of ARP (n = 818) shows high prevalence of hypertension (51%) and obesity (23%). MetS was diagnosed in 38% of participants (especially in women and 60-69 years-old individuals) without the influence of ancestry. Only 7-8% of adults had no cardio-metabolic abnormalities related to MetS. Atherogenic dyslipidemia (low HDL-cholesterol) was generally observed, including in individuals without MetS. Still, slight differences were detected between settings with a clear predominance of hypertension in Tucuruí. Hypotheses on possible genetic influence and factors (nutrition transition and environmental pollutants -mercury) are proposed for future studies. Moreover, a roadmap to MetS progression based on the most prevalent components is provided for the development of tailored interventions in the Amazon (initially, individuals would present low HDL-cholesterol levels, later progressing to increased blood pressure characterizing hypertension, and ultimately reaching MetS with obesity). Our alarming results support the need to improve our knowledge on these vulnerable populations.
RESUMO
Methylmercury (MeHg) intoxication is associated with hypertension, hypercholesterolemia, and atherosclerosis by mechanisms that are not yet fully understood. We investigated the effects of MeHg intoxication in atherosclerosis-prone (ApoE-KO) and resistant C57BL/6 mice. Mice were submitted to carotid stenosis surgery (to induce atherosclerosis faster) and received water or MeHg solution (20 mg/L) for 15 days. Tail plethysmography was performed before and after MeHg exposure. Food and MeHg solution intakes were monitored weekly. On the 15th day, mice were submitted to intravital fluorescence microscopy of mesenteric vasculature to observe in vivo leukocyte rolling and adhesion. Results showed that despite the high hair and liver Hg concentrations in the MeHg group, food and water (or MeHg solution) consumption and liver function marker levels were similar to those in controls. MeHg exposure increased total cholesterol, the atherogenic (non-HDL) fraction and systolic and diastolic blood pressure. MeHg exposure also induced inflammation, as seen by the increased rolling and adhered leukocytes in the mesenteric vasculature. Atherosclerosis lesions were more extensive in the aorta and carotid sites of MeHg-ApoE knockout mice. Surprisingly, MeHg exposure also induced atherosclerosis lesions in C57BL/6 mice, which are resistant to atherosclerosis formation. We concluded that MeHg intoxication might represent a risk for cardiovascular diseases since it accelerates atherogenesis by exacerbating several independent risk factors.
RESUMO
The search for new antiobesogenic agents is increasing because of the current obesity pandemic. Capsaicin (Caps), an exogenous agonist of the vanilloid receptor of transient potential type 1 (TRPV1), has shown promising results in the treatment of obesity. This scoping review aims to verify the pathways mediating the effects of Caps in obesity and the different methods adopted to identify these pathways. The search was carried out using data from the EMBASE, MEDLINE (PubMed), Web of Science, and SCOPUS databases. Studies considered eligible evaluated the mechanisms of action of Caps in obesity models or cell types involved in obesity. Nine studies were included and 100% (n = 6) of the in vivo studies showed a high risk of bias. Of the 9 studies, 66.6% (n = 6) administered Caps orally in the diet and 55.5% (n = 5) used a concentration of Caps of 0.01% in the diet. In vitro, the most tested concentration was 1 µM (88.9%; n = 8). Capsazepine was the antagonist chosen by 66.6% (n = 6) of the studies. Seven studies (77.8%) linked the antiobesogenic effects of Caps to TRPV1 activation and 3 (33.3%) indicated peroxisome proliferator-activated receptor (PPAR) involvement as an upstream connection to TRPV1, rather than a direct metabolic target of Caps. The main secondary effects of Caps were lower weight gain (33.3%; n = 3) or loss (22.2%; n = 2), greater improvement in lipid profile (33.3%; n = 3), lower white adipocyte adipogenesis (33.3%; n = 3), browning process activation (44.4%; n = 4), and higher brown adipocyte activity (33.3%; n = 3) compared with those of the control treatment. Some studies have shown that PPAR agonists modulate TRPV1 activity, and no study has evaluated the simultaneous antagonism of these 2 receptors. Consequently, further studies are necessary to elucidate the role of each of these signaling molecules in the antiobesogenic effects of Caps.
Assuntos
Capsaicina , Canais de Cátion TRPV , Adipócitos Marrons , Adipogenia , Capsaicina/farmacologia , Humanos , Obesidade/tratamento farmacológicoRESUMO
BACKGROUND AND AIMS: There is no clear evidence about the effects of gluten intake on obesity. It is known that gluten's effects on gut permeability are mediated by zonulin, a protein identified as pre-haptoglobin 2, a physiological regulator of the intestinal barrier. We investigated the obesogenic and inflammatory effects of gluten and its association with the haptoglobin genotype. METHODS: This was a single blinded, crossover study, including 40 overweight or obesity women free of celiac disease. Participants adopted a gluten-free diet (GFD) for 8 weeks and consumed a gluten-free muffin (GF-M) or a gluten-containing muffin (GLU-M, 24 g gluten) for 4 weeks, switching muffin type during the subsequent 4 weeks. During a follow-up period of 4 weeks we evaluated the usual diet (UD). Food diaries were collected to estimate the macronutrient intake and dietary inflammatory index (DII®). Bodyweight and composition, resting energy expenditure (REE), and cytokines were assessed. Haptoglobin alleles (Hp1 and Hp2) were genotyped to characterize zonulin expression. RESULTS: Energy and macronutrient intakes were similar during both periods, except for protein intake, which was higher during GLU-M. DII scores indicated a more inflammatory profile during the GF-M and GLU-M periods compared to UD. No differences were observed in body composition or REE between interventions when the Hp genotype was not considered. Nonetheless, those carrying the Hp2-2 genotype (overexpressing zonulin) presented lower REE and higher levels of IL6 and IL1beta only during gluten intake (GLU-M and UD) compared to age- and body mass index-matched Hp1-1 carrier. These results suggest an obesogenic and inflammatory action of gluten only in those overexpressing zonulin (Hp2-2). CONCLUSION: These results highlight the importance of zonulin as the mediator of gluten obesogenic and inflammatory effects. Our data suggest that in the presence of gluten, zonulin release is associated with a reduction of REE and an increase of inflammatory markers that are not seen in zonulin low producers.