Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 551
Filtrar
1.
Life Sci ; 356: 123035, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39222835

RESUMO

AIMS: Obesity is a global public health issue, and some studies have linked it to an increased risk of prostatic diseases. This study aimed to evaluate the effects of a high-fat diet on metabolic parameters and prostate morphology in wild-type (WT) and adiponectin knockout (KO) mice. MAIN METHODS: Male WT and KO mice were fed a control diet (CD) or high-fat diet (HFD) for 6 months. Serum metabolic parameters, inflammatory cytokines in epididymal fat tissue, dorsal prostatic lobe morphometry and histopathology were analyzed. KEY FINDINGS: CD WT and CD KO mice did not exhibit altered metabolic or prostatic parameters. However, HFD WT mice showed altered glucose and insulin tolerance even without excessive weight gain. On the other hand, HFD KO mice developed obesity, with an increase in low-density lipoprotein (11.8 ± 5.1 vs. 31.4 ± 3.6 mg/dL), high-density lipoprotein (73.4 ± 7.4 vs. 103.4 ± 2.5 mg/dL), and total cholesterol levels (126.2 ± 16.1 vs. 294.6 ± 23.2 mg/dL), a decrease in insulin levels (28.7 ± 12.2 vs. 4.6 ± 2.3 µIU/mL), and glucose and insulin resistance. We also observed that HFD KO animals display an increase in inflammatory cytokines, such as IL6, IL1ß, and IL1RA. The dorsal prostate from HFD KO animals also presented significant increases in the mast cells (1.9 ± 0,7 vs. 5,3 ± 1.5 cells/field) and Ki67 index (2.91 ± 0.6 vs. 4.7 ± 0.4 %). SIGNIFICANCE: The above findings highlight the complex interactions between adiponectin, metabolism, malnutrition, and prostate health. Metabolic deregulation combined with adipose inflammation potentially induces a proliferative and inflammatory microenvironment in the prostate gland under conditions of low adiponectin production, potentially impairing prostate morphophysiology in the context of obesity and aging.


Assuntos
Adiponectina , Citocinas , Dieta Hiperlipídica , Camundongos Knockout , Obesidade , Próstata , Animais , Masculino , Dieta Hiperlipídica/efeitos adversos , Adiponectina/metabolismo , Adiponectina/sangue , Camundongos , Citocinas/metabolismo , Próstata/patologia , Próstata/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Obesidade/etiologia , Camundongos Endogâmicos C57BL , Resistência à Insulina , Inflamação/metabolismo , Inflamação/patologia
2.
Cells ; 13(17)2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39272990

RESUMO

BACKGROUND: Obesity poses a significant global health challenge, given its association with the excessive accumulation of adipose tissue (AT) and various systemic disruptions. Within the adipose microenvironment, expansion and enrichment with immune cells trigger the release of inflammatory mediators and growth factors, which can disrupt tissues, including bones. While obesity's contribution to bone loss is well established, the direct impact of obese AT on osteoblast maturation remains uncertain. This study aimed to explore the influence of the secretomes from obese and lean AT on osteoblast differentiation and activity. METHODS: SAOS-2 cells were exposed to the secretomes obtained by culturing human subcutaneous AT from individuals with obesity (OATS) or lean patients, and their effects on osteoblasts were evaluated. RESULTS: In the presence of the OATS, mature osteoblasts underwent dedifferentiation, showing an increased proliferation accompanied by a morphological shift towards a mesenchymal phenotype, with detrimental effects on osteogenic markers and the calcification capacity. Concurrently, the OATS promoted the expression of mesenchymal and adipogenic markers, inducing the formation of cytoplasmic lipid droplets in SAOS-2 cells exposed to an adipogenic differentiation medium. Additionally, TGF-ß1 emerged as a key mediator of these effects, as the OATS was enriched with this growth factor. CONCLUSIONS: Our findings demonstrate that obese subcutaneous AT promotes the dedifferentiation of osteoblasts and increases the adipogenic profile in these cells.


Assuntos
Adipogenia , Tecido Adiposo , Desdiferenciação Celular , Obesidade , Osteoblastos , Fenótipo , Transdução de Sinais , Fator de Crescimento Transformador beta1 , Humanos , Osteoblastos/metabolismo , Osteoblastos/patologia , Obesidade/patologia , Obesidade/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Secretoma/metabolismo , Diferenciação Celular , Proliferação de Células , Osteogênese , Masculino
3.
Free Radic Biol Med ; 222: 187-198, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38897422

RESUMO

Oxidative stress and the activation of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain containing 3 (NLRP3) inflammasome have been linked to insulin resistance in skeletal muscle. In immune cells, the exacerbated generation of reactive oxygen species (ROS) activates the NLRP3 inflammasome, by facilitating the interaction between thioredoxin interacting protein (TXNIP) and NLRP3. However, the precise role of ROS/TXNIP-dependent NLRP3 inflammasome activation in skeletal muscle during obesity-induced insulin resistance remains undefined. Here, we induced insulin resistance in C57BL/6J mice by feeding them for 8 weeks with a high-fat diet (HFD) and explored whether the ROS/TXNIP/NLRP3 pathway was involved in the induction of insulin resistance in skeletal muscle. Skeletal muscle fibers from insulin-resistant mice exhibited increased oxidative stress, as evidenced by elevated malondialdehyde levels, and altered peroxiredoxin 2 dimerization. Additionally, these fibers displayed augmented activation of the NLRP3 inflammasome, accompanied by heightened ROS-dependent proximity between TXNIP and NLRP3, which was abolished by the antioxidant N-acetylcysteine (NAC). Inhibition of the NLRP3 inflammasome with MCC950 or suppressing the ROS/TXNIP/NLRP3 pathway with NAC restored insulin-dependent glucose uptake in muscle fibers from insulin-resistant mice. These findings provide insights into the mechanistic link between oxidative stress, NLRP3 inflammasome activation, and obesity-induced insulin resistance in skeletal muscle.


Assuntos
Proteínas de Transporte , Dieta Hiperlipídica , Glucose , Resistência à Insulina , Músculo Esquelético , Proteína 3 que Contém Domínio de Pirina da Família NLR , Obesidade , Estresse Oxidativo , Espécies Reativas de Oxigênio , Transdução de Sinais , Tiorredoxinas , Animais , Masculino , Camundongos , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Dieta Hiperlipídica/efeitos adversos , Furanos/farmacologia , Glucose/metabolismo , Indenos/farmacologia , Inflamassomos/metabolismo , Insulina/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Obesos , Músculo Esquelético/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Obesidade/metabolismo , Obesidade/patologia , Espécies Reativas de Oxigênio/metabolismo , Sulfonamidas , Tiorredoxinas/metabolismo , Tiorredoxinas/genética
4.
J Cell Biochem ; 125(6): e30566, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38591648

RESUMO

We investigated the effects of obesity on metabolic, inflammatory, and oxidative stress parameters in the adipose tissue of patients with fatal COVID-19. Postmortem biopsies of subcutaneous adipose tissue were obtained from 25 unvaccinated inpatients who passed from COVID-19, stratified as nonobese (N-OB; body mass index [BMI], 26.5 ± 2.3 kg m-2) or obese (OB BMI 34.2 ± 5.1 kg m-2). Univariate and multivariate analyses revealed that body composition was responsible for most of the variations detected in the metabolome, with greater dispersion observed in the OB group. Fifteen metabolites were major segregation factors. Results from the OB group showed higher levels of creatinine, myo-inositol, O-acetylcholine, and succinate, and lower levels of sarcosine. The N-OB group showed lower levels of glutathione peroxidase activity, as well as higher content of IL-6 and adiponectin. We revealed significant changes in the metabolomic profile of the adipose tissue in fatal COVID-19 cases, with high adiposity playing a key role in these observed variations. These findings highlight the potential involvement of metabolic and inflammatory pathways, possibly dependent on hypoxia, shedding light on the impact of obesity on disease pathogenesis and suggesting avenues for further research and possible therapeutic targets.


Assuntos
Autopsia , COVID-19 , Metaboloma , Obesidade , Humanos , COVID-19/metabolismo , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Obesidade/metabolismo , Obesidade/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , SARS-CoV-2/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Metabolômica/métodos , Índice de Massa Corporal , Adulto , Estresse Oxidativo , Interleucina-6/metabolismo
5.
J Cell Physiol ; 239(6): e31265, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38577921

RESUMO

The renin-angiotensin system (RAS) is an endocrine system composed of two main axes: the classical and the counterregulatory, very often displaying opposing effects. The classical axis, primarily mediated by angiotensin receptors type 1 (AT1R), is linked to obesity-associated metabolic effects. On the other hand, the counterregulatory axis appears to exert antiobesity effects through the activation of two receptors, the G protein-coupled receptor (MasR) and Mas-related receptor type D (MrgD). The local RAS in adipose organ has prompted extensive research into white adipose tissue and brown adipose tissue (BAT), with a key role in regulating the cellular and metabolic plasticity of these tissues. The MasR activation favors the brown plasticity signature in the adipose organ by improve the thermogenesis, adipogenesis, and lipolysis, decrease the inflammatory state, and overall energy homeostasis. The MrgD metabolic effects are related to the maintenance of BAT functionality, but the signaling remains unexplored. This review provides a summary of RAS counterregulatory actions triggered by Mas and MrgD receptors on adipose tissue plasticity. Focus on the effects related to the morphology and function of adipose tissue, especially from animal studies, will be given targeting new avenues for treatment of obesity-associated metabolic effects.


Assuntos
Tecido Adiposo , Proto-Oncogene Mas , Receptores Acoplados a Proteínas G , Sistema Renina-Angiotensina , Animais , Humanos , Tecido Adiposo/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Metabolismo Energético , Obesidade/metabolismo , Obesidade/patologia , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina/fisiologia , Transdução de Sinais
6.
Obes Surg ; 34(5): 1569-1574, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38502518

RESUMO

BACKGROUND: Given the importance of fibrosis in the progression of non-alcoholic fatty liver disease (NAFLD), identifying biochemical and histopathological aspects associated with its severity is important to determine the course of disease in high-risk populations. OBJECTIVES: The study aims to investigate correlations between biochemical and histopathological variables associated with the occurrence and severity of NAFLD-related liver fibrosis in individuals with obesity. METHODS: This is a cross-sectional study which enrolled 171 individuals who underwent bariatric surgery at a tertiary university hospital. Clinical, laboratory, and histopathological hepatic characteristics were analyzed. Univariate and multivariate analyses were carried out to identify factors associated with the outcomes studied (severity of fibrosis staging) through simple and multiple regression models. RESULTS: Female were 87.7%, and the mean age was 38.4 ± 9.3 years. The most common histopathological abnormalities were macrovesicular steatosis (74.9%) and hepatocellular ballooning (40.4%). In the histopathological univariate analysis, liver fibrosis significantly correlated with severities of microvesicular steatosis (p = 0.003), lobular inflammation (p = 0.001), and NAS (p < 0.001). In the multivariate analysis, the degrees of microvesicular steatosis (p < 0.001) and NAS (p < 0.001) independently correlated with fibrosis severity. In the univariate biochemical analysis, fibrosis severity significantly correlated with levels of hemoglobin A1c (p = 0.004) and glucose (p = 0.01). In the multivariate analysis, glucose levels independently correlated with liver fibrosis degree (p = 0.007). CONCLUSION: Significant and independent associations were observed between the intensities of microvesicular steatosis, NAS, and glucose levels and the severity degree of liver fibrosis in individuals with obesity.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Estudos Transversais , Obesidade Mórbida/cirurgia , Fígado/patologia , Cirrose Hepática/complicações , Obesidade/complicações , Obesidade/patologia , Glucose , Biópsia
7.
Mol Neurobiol ; 61(9): 6366-6382, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38296901

RESUMO

Obesity causes inflammation in the adipose tissue and can affect the central nervous system, leading to oxidative stress and mitochondrial dysfunction. Therefore, it becomes necessary to seek new therapeutic alternatives. Gold nanoparticles (GNPs) could take carnitine to the adipose tissue, thus increasing fatty acid oxidation, reducing inflammation, and, consequently, restoring brain homeostasis. The objective of this study was to investigate the effects of GNPs associated with carnitine on the neurochemical parameters of obesity-induced mice. Eighty male Swiss mice that received a normal lipid diet (control group) or a high-fat diet (obese group) for 10 weeks were used. At the end of the sixth week, the groups were divided for daily treatment with saline, GNPs (70 µg/kg), carnitine (500 mg/kg), or GNPs associated with carnitine, respectively. Body weight was monitored weekly. At the end of the tenth week, the animals were euthanized and the mesenteric fat removed and weighed; the brain structures were separated for biochemical analysis. It was found that obesity caused oxidative damage and mitochondrial dysfunction in brain structures. Treatment with GNPs isolated reduced oxidative stress in the hippocampus. Carnitine isolated decreased the accumulation of mesenteric fat and oxidative stress in the hippocampus. The combination of treatments reduced the accumulation of mesenteric fat and mitochondrial dysfunction in the striatum. Therefore, these treatments in isolation, become a promising option for the treatment of obesity.


Assuntos
Encéfalo , Carnitina , Modelos Animais de Doenças , Ouro , Nanopartículas Metálicas , Obesidade , Estresse Oxidativo , Animais , Carnitina/farmacologia , Carnitina/administração & dosagem , Carnitina/uso terapêutico , Ouro/farmacologia , Masculino , Obesidade/tratamento farmacológico , Obesidade/patologia , Obesidade/complicações , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Dieta Hiperlipídica , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/patologia , Lesões Encefálicas/metabolismo , Peso Corporal/efeitos dos fármacos
8.
Osteoporos Int ; 35(4): 575-588, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38055051

RESUMO

PURPOSE: Osteoporosis is a metabolic bone disease characterized by decreased bone strength and mass, which predisposes patients to fractures and is associated with high morbidity and mortality. Like osteoporosis, obesity and diabetes are systemic metabolic diseases associated with modifiable risk factors and lifestyle, and their prevalence is increasing. They are related to decreased quality of life, functional loss and increased mortality, generating high costs for health systems and representing a worldwide public health problem. Growing evidence reinforces the role of bone marrow adipose tissue (BMAT) as an influential factor in the bone microenvironment and systemic metabolism. Given the impact of obesity and diabetes on metabolism and their possible effect on the bone microenvironment, changes in BMAT behavior may explain the risk of developing osteoporosis in the presence of these comorbidities. METHODS: This study reviewed the scientific literature on the behavior of BMAT in pathological metabolic conditions, such as obesity and diabetes, and its potential involvement in the pathogenesis of bone fragility. RESULTS: Published data strongly suggest a relationship between increased BMAT adiposity and the risk of bone fragility in the context of obesity and diabetes. CONCLUSION: By secreting a broad range of factors, BMAT modulates the bone microenvironment and metabolism, ultimately affecting skeletal health. A better understanding of the relationship between BMAT expansion and metabolic disturbances observed in diabetic and obese patients will help to identify regulatory pathways and new targets for the treatment of bone-related diseases, with BMAT as a potential therapeutic target.


Assuntos
Diabetes Mellitus , Osteoporose , Humanos , Medula Óssea/patologia , Densidade Óssea , Qualidade de Vida , Tecido Adiposo/patologia , Obesidade/complicações , Obesidade/patologia , Osteoporose/epidemiologia , Osteoporose/etiologia , Osteoporose/metabolismo
9.
J Allergy Clin Immunol ; 153(3): 860-867.e1, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38048884

RESUMO

BACKGROUND: Maternal overweight and obesity have been associated with an increased risk of atopic dermatitis (AD) in the offspring, but the underlying mechanisms are unclear. Vernix caseosa (VC) is a proteolipid material covering the fetus produced during skin development. However, whether maternal prepregnancy weight excess influences fetal skin development is unknown. Characterizing the VC of newborns from mothers with prepregnancy overweight and obesity might reveal AD-prone alterations during fetal skin development. OBJECTIVE: We sought to explore AD biomarkers and staphylococcal loads in VC from the offspring of mothers who were overweight/obese (O/O) before pregnancy versus in those from offspring of normal weight mothers. METHODS: The VC of newborns of 14 O/O and 12 normal weight mothers were collected immediately after birth. Biomarkers were determined by ELISA and staphylococcal species by quantitative PCR. RESULTS: The VC from the O/O group showed decreased expression of skin barrier proteins (filaggrin and loricrin) and increased levels of proinflammatory biomarkers (IgA, thymic stromal lymphopoietin [TSLP], S100A8, IL-25, and IL-33). No differences in concentrations of antimicrobial peptides and enzymes were detected. The VC from the O/O group had a lower Staphylococcus epidermidis and Staphylococcus hominis commensal bacterial load, whereas Staphylococcus aureus bacterial load was not significantly different between the 2 groups. Maternal body mass index was negatively correlated with VC filaggrin expression and S epidermidis load and was positively associated with TSLP concentration. One-year follow-up established that the offspring of O/O mothers had a higher incidence of AD that was specifically linked with decreased VC filaggrin expression and lower S epidermidis load. CONCLUSIONS: VC from neonates of mothers with prepregnancy overweight and obesity exhibit skin barrier molecular alterations and staphylococcal dysbiosis that suggest early mechanistic clues to this population's increased risk of AD.


Assuntos
Dermatite Atópica , Obesidade Materna , Verniz Caseoso , Humanos , Recém-Nascido , Feminino , Gravidez , Dermatite Atópica/patologia , Proteínas Filagrinas , Obesidade Materna/metabolismo , Obesidade Materna/patologia , Verniz Caseoso/metabolismo , Sobrepeso , Pele/patologia , Citocinas/metabolismo , Linfopoietina do Estroma do Timo , Obesidade/patologia , Biomarcadores/metabolismo
10.
Int J Mol Sci ; 24(13)2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37445834

RESUMO

The present study investigated the effect of gelatin-based nanoparticles (EPG) loaded with a carotenoid-rich crude extract (CE) on systemic and adipose tissue inflammatory response in a model with inflammation induced by a high glycemic index and high glycemic load diet (HGLI). Nanoparticles synthesized were characterized by different physical and chemical methods. The in vivo investigation evaluated Wistar rats (n = 20, 11 days, adult male with 21 weeks) subdivided into untreated (HGLI diet), conventional treatment (nutritionally adequate diet), treatment 1 (HGLI + crude extract (12.5 mg/kg)), and treatment 2 (HGLI + EPG (50 mg/kg)) groups. Dietary intake, caloric intake and efficiency, weight, inflammatory cytokines tissue concentration, visceral adipose tissue (VAT) weight, histopathological analysis, and antioxidant activity in plasma and VAT were investigated. EPG showed the same physical and chemical characteristics as previous batches (95.2 nm, smooth surface, and chemical interactions between materials). The EPG-treated group was the only group promoting negative ∆dietary intake, ∆caloric efficiency, and ∆weight. In addition, it presented a significant reduction (p < 0.05) in IL-6 and leptin levels and a greater presence of multilocular adipocytes. The results suggest that EPG can act as a nutraceutical in adjuvant therapy for treating inflammatory diseases associated with adipose tissue accumulation.


Assuntos
Citocinas , Obesidade , Ratos , Animais , Masculino , Ratos Wistar , Obesidade/patologia , Citocinas/farmacologia , Gelatina/farmacologia , Tecido Adiposo/patologia , Adipócitos , Hipertrofia/patologia , Carotenoides/farmacologia
11.
Braz J Med Biol Res ; 56: e12547, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36995873

RESUMO

The main goal of this study was to determine whether oxidative imbalance mediated by AT1 receptor (AT1R) is responsible for deleterious endothelial responses to mental stress (MS) in overweight/obese class I men. Fifteen overweight/obese men (27±7 years old; 29.8±2.6 kg/m2) participated in three randomized experimental sessions with oral administration of the AT1R blocker olmesartan (40 mg; AT1R blockade) or ascorbic acid (AA; 3g) infusion or placebo [both intravenously (0.9% NaCl) and orally]. After two hours, endothelial function was determined by flow-mediated dilation (FMD) before (baseline), 30 min (30MS), and 60 min (60MS) after a five-minute acute MS session (Stroop Color Word Test). Blood was collected before (baseline), during MS, and 60 min after MS for redox homeostasis profiling: lipid peroxidation (TBARS; thiobarbituric acid reactive species), protein carbonylation, and catalase activity by colorimetry and superoxide dismutase (SOD) activity by an ELISA kit. At the placebo session, FMD significantly decreased 30MS (P=0.05). When compared to baseline, TBARS (P<0.02), protein carbonylation (P<0.01), catalase (P<0.01), and SOD (P<0.01) increased during the placebo session. During AT1R blockade, FMD increased 30 min after MS (P=0.01 vs baseline; P<0.01 vs placebo), while AA infusion increased FMD only 60 min after MS. No differences were observed during MS with the AT1R blockade and AA regarding TBARS, protein carbonylation, catalase, and SOD. AT1R-mediated redox imbalances played an important role in endothelial dysfunction to mental stress.


Assuntos
Obesidade , Estresse Psicológico , Humanos , Estresse Psicológico/patologia , Células Endoteliais/patologia , Estresse Oxidativo , Masculino , Obesidade/complicações , Obesidade/metabolismo , Obesidade/patologia , Receptor Tipo 1 de Angiotensina/metabolismo
12.
Int J Mol Sci ; 24(5)2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36902320

RESUMO

Obesity causes low-grade inflammation that results in the development of comorbidities. In people with obesity, exacerbation of gastric lesion severity and delayed healing may aggravate gastric mucosal lesions. Accordingly, we aimed to evaluate the citral effects on gastric lesion healing in eutrophic and obese animals. C57Bl/6 male mice were divided into two groups: animals fed a standard diet (SD) or high-fat diet (HFD) for 12 weeks. Gastric ulcers were induced using acetic acid (80%) in both groups. Citral (25, 100, or 300 mg/kg) was administered orally for 3 or 10 days. A vehicle-treated negative control (1% Tween 80, 10 mL/kg) and lansoprazole-treated (30 mg/kg) were also established. Lesions were macroscopically examined by quantifying regenerated tissue and ulcer areas. Matrix metalloproteinases (MMP-2 and -9) were analyzed by zymography. The ulcer base area between the two examined periods was significantly reduced in HFD 100 and 300 mg/kg citral-treated animals. In the 100 mg/kg citral-treated group, healing progression was accompanied by reduced MMP-9 activity. Accordingly, HFD could alter MMP-9 activity, delaying the initial healing phase. Although macroscopic changes were undetectable, 10-day treatment with 100 mg/kg citral exhibited improved scar tissue progression in obese animals, with reduced MMP-9 activity and modulation of MMP-2 activation.


Assuntos
Metaloproteinase 2 da Matriz , Úlcera Gástrica , Camundongos , Animais , Masculino , Úlcera Gástrica/patologia , Metaloproteinase 9 da Matriz/farmacologia , Úlcera/patologia , Dieta Hiperlipídica , Obesidade/patologia , Mucosa Gástrica/patologia
13.
Adv Biol (Weinh) ; 7(8): e2200337, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36950759

RESUMO

Obesity often results in severe negative health consequences and represents a growing issue for global health. Reducing food intake is a crucial factor for weight loss. Intermittent fasting is a relatively new intervention that contributes to weight reduction. Considering the intimate relationship between obesity and inflammatory pathologies with gut microbiota alterations, a systematic review of the literature was herein conducted to elucidate the relationship between time-restricted food intake and gut microbiota diversity in humans. Searches are carried out in three databases (PubMed, MedLine/OVID, and Academic Search Complete) between April 2019 and April 2022. Nine studies (all with longitudinal design) were identified as eligible by presenting data about the impact of intermittent fasting schemes on gut microbiota. At the phylum level, Firmicutes and Bacteroidetes increase throughout follow-ups, while 16 bacteria genera change their abundance in response to intermittent fasting. Finally, some genera associated with clinical predictors such as weight change, abdominal circumference, and metabolic variables were reported. Changes induced by fasting schemes positively impact the diversity and abundance of gut microbiota and the biomarkers described here. However, the changes previously reported have been studied in short periods and some return to their basal state after fasting intervention.


Assuntos
Bactérias , Microbioma Gastrointestinal , Jejum Intermitente , Obesidade , Humanos , Animais , Obesidade/microbiologia , Obesidade/patologia , Obesidade/terapia , Inflamação/microbiologia , Bactérias/classificação , Bactérias/isolamento & purificação
14.
Life Sci ; 316: 121416, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36690245

RESUMO

AIMS: Blood vessels are surrounded by perivascular adipose tissue (PVAT), which plays an important role in vascular tonus regulation due to its anticontractile effect; however, this effect is impaired in obesity. We previously demonstrated that miRNA-22 is involved in obesity-related metabolic disorders. However, the impact of miRNA-22 on vascular reactivity and PVAT function is unknown. AIM: To investigate the role of miRNA-22 on vascular reactivity and its impact on obesity-induced PVAT dysfunction. MAIN METHODS: Wild-type and miRNA-22 knockout (KO) mice were fed a control or a high-fat (HF) diet. To characterize the vascular response, concentration-responses curves to noradrenaline were performed in PVAT- or PVAT+ thoracic aortic rings in absence and presence of L-NAME. Expression of adipogenic and thermogenic markers and NOS isoforms were evaluated by western blotting or qPCR. KEY FINDINGS: HF diet and miRNA-22 deletion reduced noradrenaline-induced contraction in PVAT- aortic rings. Additionally, miRNA-22 deletion increased noradrenaline-induced contraction in PVAT+ aortic rings without affecting its sensitivity; however, this effect was not observed in miRNA-22 KO mice fed a HF diet. Interestingly, miRNA-22 deletion reduced the contraction of aortic rings to noradrenaline via a NOS-dependent mechanism. Moreover, HF diet abolished the NOS-mediated anticontractile effect of PVAT, which was attenuated by miRNA-22 deletion. Mechanistically, we found that PVAT from miRNA-22 KO mice fed a HF diet presented increased protein expression of nNOS. SIGNIFICANCE: These results suggest that miRNA-22 is important for aorta reactivity under physiological circumstances and its deletion attenuates the loss of the NOS-mediated anticontractile effect of PVAT in obesity.


Assuntos
Tecido Adiposo , Aorta , MicroRNAs , Obesidade , Animais , Camundongos , Tecido Adiposo/metabolismo , Aorta/metabolismo , MicroRNAs/metabolismo , Norepinefrina/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Vasoconstrição
15.
Artigo em Inglês | MEDLINE | ID: mdl-36113920

RESUMO

INTRODUCTION: Paradoxical vocal fold movement (PVFM) is a respiratory disorder related to inadequate movement of vocal folds during inspiration or expiration. Its epidemiology and pathogenesis are unknown. The present study describes the standardization of the examination performed in our service and the main endoscopic changes found, evaluating the prevalence of PVFM in patients with suggestive symptoms and describing the association of PVFM with asthma and other diseases. MATERIALS AND METHODS: Retrospective observational study of a series of cases over a 13-year period - adult patients referred for outpatient bronchoscopy due to suspected PVFM. RESULTS: We analyzed 1131 laryngoscopies performed on patients referred for suspicion of PVFM from May 2006 to June 2019. Of these, 368 cases were excluded from the study. A total of 255 patients (33%) had a confirmed diagnosis of PVFM, 224 women (88%). The most frequent comorbidities found were asthma (62%), rhinitis (45%), gastro-oesophageal reflux disease (45%), obesity (24%), and psychiatric disorders (19%). Among the endoscopic findings concomitant with the diagnosis of PVDM, we highlight posterior laryngitis (71%), diseases of the nasal septum (18%), nasal polyps (7%). DISCUSSION: Female sex is more affected. There are several associations with other diseases, the main one being asthma, followed by rhinitis and psychiatric disorders. Obesity appears as a comorbidity in 24% of patients, as does sleep apnoea in 13%. Posterior laryngitis was the most common endoscopic finding. PVFM is an underdiagnosed disease, little known as it is a rare entity that still needs prospective studies. Exam standardization is important.


Assuntos
Asma , Laringite , Rinite , Adulto , Asma/complicações , Asma/diagnóstico , Asma/epidemiologia , Feminino , Humanos , Laringite/patologia , Obesidade/patologia , Estudos Prospectivos , Prega Vocal
16.
Cells ; 11(12)2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35741012

RESUMO

Obesity is characterized by an increase in body weight associated with an exaggerated enlargement of the adipose tissue. Obesity has serious negative effects because it is associated with multiple pathological complications such as type 2 diabetes mellitus, cardiovascular diseases, cancer, and COVID-19. Nowadays, 39% of the world population is obese or overweight, making obesity the 21st century epidemic. Obesity is also characterized by a mild, chronic, systemic inflammation. Accumulation of fat in adipose tissue causes stress and malfunction of adipocytes, which then initiate inflammation. Next, adipose tissue is infiltrated by cells of the innate immune system. Recently, it has become evident that neutrophils, the most abundant leukocytes in blood, are the first immune cells infiltrating the adipose tissue. Neutrophils then get activated and release inflammatory factors that recruit macrophages and other immune cells. These immune cells, in turn, perpetuate the inflammation state by producing cytokines and chemokines that can reach other parts of the body, creating a systemic inflammatory condition. In this review, we described the recent findings on the role of neutrophils during obesity and the initiation of inflammation. In addition, we discuss the involvement of neutrophils in the generation of obesity-related complications using diabetes as a prime example.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Resistência à Insulina , COVID-19/complicações , Diabetes Mellitus Tipo 2/patologia , Humanos , Inflamação/patologia , Neutrófilos/patologia , Obesidade/patologia
17.
Obes Surg ; 32(8): 2658-2663, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35670949

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a challenge in public health, as the prevalence of obesity and overweight has been increasing. It has been observed that serum ferritin (SF) levels are commonly elevated in NAFLD patients. PURPOSE: To assess the relationship between SF levels and NAFLD, exploring the role of SF as a non-invasive marker of NAFLD. METHODS: Clinical, anthropometric, laboratory, and histological data of patients with obesity who underwent bariatric surgery in a reference center in Brazil were retrospectively evaluated. Data were collected in the preoperative period up to the first year postoperatively. RESULTS: A total of 431 patients were analyzed. The prevalence of hyperferritinemia was 18% in the preoperative period and 14% 1 year after the surgery. After multiple regression analysis, elevated SF was not an independent predictor of steatosis, non-alcoholic steatohepatitis (NASH), or liver fibrosis. CONCLUSIONS: Increased SF levels are common in patients with NAFLD; however, SF was not considered an independent predictor of steatosis, NASH, or fibrosis.


Assuntos
Cirurgia Bariátrica , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Biópsia , Ferritinas , Humanos , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/patologia , Obesidade Mórbida/cirurgia , Estudos Retrospectivos
18.
Inflamm Res ; 71(7-8): 759-770, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35648156

RESUMO

Type 2 diabetes mellitus (T2DM) is an important chronic disease around the world, and according to the World Health Organization, it is the 9th principal cause of global death. This pathology is characterized by high levels of circulating glucose as a result of insulin resistance, and it is well stated that inflammation related to obesity is directly associated with the development of the disease. The purinergic signalling is involved in both pancreatic destruction, which impairs insulin secretion, and the cytokine production that favors insulin resistance in T2DM. In this review, the purinergic signalling aspects will be discussed, showing the impact of the enzymes, nucleotides, nucleosides, and receptors of this system and the cytokines that result in inflammation, in the development and progression of T2DM, besides, pointing the purinergic receptors as a possible therapeutic approach.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Diabetes Mellitus Tipo 2/patologia , Humanos , Inflamação/patologia , Obesidade/patologia , Transdução de Sinais
19.
Arch. latinoam. nutr ; Arch. latinoam. nutr;72(2): 100-108, jun. 2022. ilus
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1381416

RESUMO

Las investigaciones realizadas durante el último siglo relacionadas con la descripción de la Microbiota Intestinal (MI) sugieren una relación concreta entre su composición y la salud del huésped. Su desregulación denominada disbiosis intestinal ha sido asociada a distintos tipos de enfermedades gastrointestinales, metabólicas, oncológicas e incluso psiquiátricas. Destacan numerosos reportes que han informado la condición de disbiosis en la obesidad, tanto en modelos animales como humanos de distintos grupos etarios y regiones del mundo. A su vez, la composición del microbioma también ha logrado asociarse a las diferentes comorbilidades de la obesidad, postulando que la MI posee influencia en la disfunción del tejido adiposo (TA), entendiendo que corresponde al principal modulador de la patogénesis de la obesidad. Sin embargo, aún no es posible establecer una explicación mecanicista plausible. Actualmente, la utilización de tecnologías multiómicas, junto con la evaluación de variables fisiológicas, nos podrían proporcionar una mejor comprensión a la incógnita planteada. Frente a esto, el presente trabajo tiene como objetivo revisar los últimos avances en la comprensión de la influencia de la microbiota intestinal en el TA y su contribución a los mecanismos relacionados con la patogénesis de la obesidad. Entre los principales mecanismos identificados, la evidencia reporta nexos fisiológicos entre la composición de la MI y la modulación de inflamación, permeabilidad intestinal y adipogénesis. Las vías implicadas derivan de la influencia de la disbiosis intestinal en el accionar de ácidos grasos de cadena corta, claudinas, macrófagos, oligosacáridos, entre otros. Los mecanismos implicados, principalmente estudiados en modelos animales, deberían ser considerados para su evaluación en próximos estudios longitudinales y experimentales en humanos con el fin de obtener una mayor comprensión sobre la implicancia de cada mecanismo en la patogenia global de la obesidad(AU)


The investigations carried out during the last century related to the description of the Gut Microbiota (GM) suggest a concrete relationship between its composition and the health of the host. Its deregulation called intestinal dysbiosis has been associated with different types of gastrointestinal, metabolic, oncological and even psychiatric diseases. Numerous reports that have described the condition of dysbiosis in obesity stand out, both in animal and human models of different age groups and regions of the world. In turn, the composition of the microbiome has also been associated with the different comorbidities of obesity, postulating that MI has an influence on adipose tissue (AT) dysfunction, understanding that it corresponds to the main modulator of the pathogenesis of obesity. However, it is not yet possible to establish a plausible mechanistic explanation. Currently, the use of multi-omics technologies, together with the evaluation of physiological variables, could provide us with a better understanding of the question raised. In view of this, this review aims to review the latest advances in understanding the influence of the intestinal microbiota on AT and its contribution to the mechanisms related to the pathogenesis of obesity. Among the main mechanisms identified, the evidence reports physiological links between the composition of GM and the modulation of inflammation, intestinal permeability and adipogenesis. The pathways involved derive from the influence of intestinal dysbiosis on the action of short-chain fatty acids, claudins, macrophages, oligosaccharides, among others. The mechanisms involved, mainly studied in animal models, should be considered for evaluation in future longitudinal and experimental studies in humans in order to obtain a better understanding of the implication of each mechanism in the global pathogenesis of obesity(AU)


Assuntos
Tecido Adiposo , Microbioma Gastrointestinal , Obesidade/patologia , Metabolismo Energético , Adipogenia , Disbiose , Gastroenteropatias
20.
Int J Obes (Lond) ; 46(9): 1582-1586, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35597848

RESUMO

BACKGROUND: Syndromic obesity (SO) refers to obesity with additional phenotypes, including intellectual disability (ID)/developmental delay (DD), dysmorphic features, or organ-specific abnormalities. SO is rare, has high phenotypic variability, and frequently follows a monogenic pattern of inheritance. However, the genetic etiology of most cases of SO has not been elucidated. SUBJECTS AND METHODS: In this study, we investigated 20 SO patients by whole-exome sequencing (WES) trios to identify causal genetic variants. RESULTS: 4/20 patients had negative results for array comparative genomic hybridization (aCGH) analyses. In the remaining 15 patients, in addition to SNVs and indels, CNVs were also evaluated. Pathogenic/likely pathogenic (P/LP) SNVs/indels were detected in 6/20 patients (involving MED13L, AHDC1, EHMT1, MYT1L, GRIA3, and SETD1A), while two patients carried an inherited VUS. In addition, P/LP CNVs were observed in 3/15 patients (involving SATG2, KIAA0442, and MEIS2). CONCLUSIONS: All nine detected P/LP variants involved genes already known to lead to syndromic ID/DD; however, for only two genes (EHMT1 and MYT1L) is the link with obesity well established. This is the first study applying a comprehensive genomic investigation of an SO cohort, showing a high diagnostic yield (~47%). Additionally, our findings suggested that several known ID/DD genes may also predispose individuals to SO.


Assuntos
Deficiências do Desenvolvimento , Deficiência Intelectual , Criança , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Proteínas de Ligação a DNA/genética , Deficiências do Desenvolvimento/genética , Histona-Lisina N-Metiltransferase/genética , Humanos , Deficiência Intelectual/genética , Obesidade/genética , Obesidade/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA