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Objective: To investigate the role of leptin in regulating cell inflammation and protecting myocardium after myocardial ischemia-reperfusion injury in rats through signaling pathway at tissue and molecular protein levels. Methods: Healthy female SD rats were randomly divided into 4 groups, which were sham, I/R group, leptin low-dose intervention group, and high-dose intervention group (40 µg/kg and 80 µg/kg, respectively). Cardiac hemodynamics, myocardial enzymology, inflammatory indices, and pathological changes were observed. Western blot was used to observe the expression of PI3K, AKT, and NFκB protein by leptin. Results: Leptin can improve the hemodynamics of cardiac ischemia-reperfusion rats, improve the expression of myocardial enzymology, reduce the release of cardiac and serum inflammatory factors, increased PI3k, AKT, and NFκB expression, and reduce the occurrence of inflammation from the perspective of gross pathology, thus protecting the body. Conclusion: Leptin pretreatment can reduce MIRI injury, and the protective mechanism may be that leptin upregulates PI3K-AKT-NFκB expression in myocardial tissue to reduce inflammation and promote repair of I/R injury.
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Inflamación/metabolismo , Leptina , Daño por Reperfusión Miocárdica , Sustancias Protectoras , Animales , Fosfatidilinositol 3-Quinasa Clase Ib , Femenino , Leptina/inmunología , Leptina/metabolismo , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismo , Miocardio/enzimología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
BACKGROUND: Leptin plays an important role in the regulation of the immune response. There is a physiological surge of leptin in rodents during the neonatal period, which has mainly been studied in the context of brain development. However, little is known about the effects of this neonatal leptin surge on immunity. Therefore, we investigated whether blocking this leptin surge could affect several immune functions. METHODS: Male and female rats were injected subcutaneously with 5 mg/Kg/day of rat pegylated super leptin antagonist during the neonatal period (PND5-9). On the peripubertal period, relevant functions as well as cytokine release by spleen leukocytes were studied in these animals. RESULTS: The results showed that the animals significantly display an impaired anti-tumor NK activity and chemotactic and proliferation capacity of lymphocytes in response to mitogens. In addition, several cytokine concentrations, released under mitogen-stimulated conditions, were also altered. CONCLUSION: In conclusion, the neonatal leptin surge seems to be involved in the establishment of an adequate immune response and cytokine profile, which are crucial for the maintenance of a healthy life.
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Crecimiento y Desarrollo , Leptina , Animales , Animales Recién Nacidos/crecimiento & desarrollo , Animales Recién Nacidos/inmunología , Citocinas/análisis , Citocinas/inmunología , Femenino , Crecimiento y Desarrollo/inmunología , Inmunidad/inmunología , Inmunidad/fisiología , Péptidos y Proteínas de Señalización Intercelular/inmunología , Leptina/inmunología , Masculino , Ratas/inmunologíaRESUMEN
Obesity is one of the foremost risk factors in coronavirus infection resulting in severe illness and mortality as the pandemic progresses. Obesity is a well-known predisposed chronic inflammatory condition. The dynamics of obesity and its impacts on immunity may change the disease severity of pneumonia, especially in acute respiratory distress syndrome, a primary cause of death from SARS-CoV-2 infection. The adipocytes of adipose tissue secret leptin in proportion to individuals' body fat mass. An increase in circulating plasma leptin is a typical characteristic of obesity and correlates with a leptin-resistant state. Leptin is considered a pleiotropic molecule regulating appetite and immunity. In immunity, leptin functions as a cytokine and coordinates the host's innate and adaptive responses by promoting the Th1 type of immune response. Leptin induced the proliferation and functions of antigen-presenting cells, monocytes, and T helper cells, subsequently influencing the pro-inflammatory cytokine secretion by these cells, such as TNF-α, IL-2, or IL-6. Leptin scarcity or resistance is linked with dysregulation of cytokine secretion leading to autoimmune disorders, inflammatory responses, and increased susceptibility towards infectious diseases. Therefore, leptin activity by leptin long-lasting super active antagonist's dysregulation in patients with obesity might contribute to high mortality rates in these patients during SARS-CoV-2 infection. This review systematically discusses the interplay mechanism between leptin and inflammatory cytokines and their contribution to the fatal outcomes in COVID-19 patients with obesity.
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COVID-19/patología , Leptina/inmunología , Obesidad/patología , SARS-CoV-2/inmunología , Adipocitos/metabolismo , Células Presentadoras de Antígenos/inmunología , COVID-19/mortalidad , Citocinas/inmunología , Susceptibilidad a Enfermedades/patología , Humanos , Leptina/sangre , Monocitos/inmunología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Células TH1/inmunologíaRESUMEN
Leptin is an important regulator of basal metabolism and food intake, with a pivotal role in obesity. Leptin exerts many different actions on various tissues and systems, including cancer, and is considered as a linkage between metabolism and the immune system. During the last decades, obesity and leptin have been associated with the initiation, proliferation and progression of many types of cancer. Obesity is also linked with complications and mortality, irrespective of the therapy used, affecting clinical outcomes. However, some evidence has suggested its beneficial role, called the "obesity paradox", and the possible antitumoral role of leptin. Recent data regarding the immunotherapy of cancer have revealed that overweight leads to a more effective response and leptin may probably be involved in this beneficial process. Since leptin is a positive modulator of both the innate and the adaptive immune system, it may contribute to the increased immune response stimulated by immunotherapy in cancer patients and may be proposed as a good actor in cancer. Our purpose is to review this dual role of leptin in cancer, as well as trying to clarify the future perspectives of this adipokine, which further highlights its importance as a cornerstone of the immunometabolism in oncology.
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Inmunidad Adaptativa , Inmunoterapia , Leptina/inmunología , Proteínas de Neoplasias/inmunología , Neoplasias/inmunología , Neoplasias/terapia , Animales , Humanos , Obesidad/inmunologíaRESUMEN
INTRODUCTION: Endometriosis is an inflammatory condition, affecting mainly women of reproductive age. Leptin is a regulator of food intake and energy expenditure, posing pleiotropic actions, and regulating immunity and fertility. The aim of this study was to systematically review the literature regarding leptin concentrations in biological fluids and tissues of women with endometriosis, and to investigate and propose a possible role of leptin in the pathophysiology of endometriosis. MATERIALS AND METHODS: A systematic search of the literature was conducted in two electronic databases (MEDLINE, COCHRANE) and grey literature for original research articles on humans, published in any language. RESULTS: Twenty-nine studies with 1291 women with endometriosis and 1664 controls were included in the systematic review. Peritoneal fluid and follicular fluid leptin concentrations were higher in endometriosis compared with control group [mean difference (MD) 7.10, 95 % confidence interval (CI) 4.76 to 9.44 ng/mL, 18 studies), (MD 1.35, 95 % CI 0.54-2.17 ng/ml, 2 studies) respectively. No differences were evident in serum (MD 0.92, 95 % CI -0.84 to 2.68 ng/mL, 12 studies) or plasma (MD -0.95, 95 % CI -4.63 to 2.72 ng/mL, 3 studies) between the groups. No meta-analysis was conducted for ovarian tissue leptin (2 studies). CONCLUSIONS: This meta-analysis provided evidence for increased leptin concentrations in both peritoneal fluid and follicular fluid of women with endometriosis compared with control; these differences were not present in the serum or plasma. The above results support a potential pathophysiologic role for leptin in the local microenvironment while declines its use as a blood diagnostic marker. Furthermore, we propose a possible role of leptin in the pathophysiology of endometriosis.
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Endometriosis/inmunología , Leptina/análisis , Líquido Ascítico/inmunología , Líquido Ascítico/metabolismo , Líquido Ascítico/patología , Biomarcadores/análisis , Biomarcadores/metabolismo , Estudios de Casos y Controles , Endometriosis/diagnóstico , Endometriosis/patología , Femenino , Líquido Folicular/inmunología , Líquido Folicular/metabolismo , Humanos , Leptina/inmunología , Leptina/metabolismoRESUMEN
The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.
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Autoanticuerpos , Trastornos de Alimentación y de la Ingestión de Alimentos/inmunología , Microbioma Gastrointestinal/inmunología , Ghrelina/inmunología , Insulina/inmunología , Leptina/inmunología , Hormonas Estimuladoras de los Melanocitos/inmunología , Neuropéptido Y/inmunología , Trastornos de Alimentación y de la Ingestión de Alimentos/microbiología , HumanosRESUMEN
The recent pandemic Sars-CoV2 infection and studies on previous influenza epidemic have drawn attention to the association between the obesity and infectious diseases susceptibility and worse outcome. Metabolic complications, nutritional aspects, physical inactivity, and a chronic unbalance in the hormonal and adipocytokine microenvironment are major determinants in the severity of viral infections in obesity. By these pleiotropic mechanisms obesity impairs immune surveillance and the higher leptin concentrations produced by adipose tissue and that characterize obesity substantially contribute to such immune response dysregulation. Indeed, leptin not only controls energy balance and body weight, but also plays a regulatory role in the interplay between energy metabolism and immune system. Since leptin receptor is expressed throughout the immune system, leptin may exert effects on cells of both innate and adaptive immune system. Chronic inflammatory states due to metabolic (i.e., obesity) as well as infectious diseases increase leptin concentrations and consequently lead to leptin resistance further fueling inflammation. Multiple factors, including inflammation and ER stress, contribute to leptin resistance. Thus, if leptin is recognized as one of the adipokines responsible for the low grade inflammation found in obesity, on the other hand, impairments of leptin signaling due to leptin resistance appear to blunt the immunologic effects of leptin and possibly contribute to impaired vaccine-induced immune responses. However, many aspects concerning leptin interactions with inflammation and immune system as well as the therapeutical approaches to overcome leptin resistance and reduced vaccine effectiveness in obesity remain a challenge for future research.
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Leptina/inmunología , Leptina/metabolismo , Obesidad/complicaciones , Obesidad/virología , Virosis/complicaciones , Animales , Antivirales/uso terapéutico , COVID-19/complicaciones , COVID-19/inmunología , COVID-19/metabolismo , Metabolismo Energético/inmunología , Humanos , Sistema Inmunológico/metabolismo , Sistema Inmunológico/virología , Obesidad/inmunología , Obesidad/metabolismo , Vacunas Virales/uso terapéutico , Virosis/tratamiento farmacológico , Virosis/inmunología , Virosis/metabolismo , Tratamiento Farmacológico de COVID-19RESUMEN
PURPOSE: The aim of this study was to investigate the possible link between different types of systemic sclerosis-specific antinuclear antibodies, adipokines and endothelial molecules which were recently found to have a pathogenic significance in systemic sclerosis. MATERIALS/METHODS: Serum concentration of adiponectin, resistin, leptin, endothelin-1, fractalkine and galectin-3 were determined in the sera of patients with systemic sclerosis (n â= â100) and healthy controls (n â= â20) using ELISA. RESULTS: The following associations between antinuclear antibodies and increased serum concentrations were identified: anticentromere antibodies with endothelin-1 (p â< â0.0001; mean level in patients 2.21 vs control group 1.31 âpg/ml), anti-topoisomerase I antibodies with fractalkine (p â< â0.0001; 3.68 vs 1.68 âng/ml) and galectin-3 (p â= â0.0010, 6.39 vs 3.26 âng/ml). Anti-RNA polymerase III antibodies were associated with increased resistin (p â< â0.0001; 15.13 vs 8.54 âng/ml) and decreased adiponectin (p â< â0.0001; 2894 vs 8847 âng/ml). CONCLUSION: In systemic sclerosis metabolic and vascular factors may serve as mediators between immunological abnormalities and non-immune driven clinical symptoms.
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Anticuerpos Antinucleares/inmunología , Biomarcadores/sangre , Esclerodermia Sistémica/patología , Adipoquinas/sangre , Adipoquinas/inmunología , Adiponectina/sangre , Adiponectina/inmunología , Anticuerpos Antinucleares/sangre , Proteínas Sanguíneas/inmunología , Estudios de Casos y Controles , Quimiocina CX3CL1/sangre , Quimiocina CX3CL1/inmunología , Endotelina-1/sangre , Endotelina-1/inmunología , Femenino , Estudios de Seguimiento , Galectinas/sangre , Galectinas/inmunología , Humanos , Leptina/sangre , Leptina/inmunología , Masculino , Persona de Mediana Edad , Pronóstico , Resistina/sangre , Resistina/inmunología , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/inmunologíaRESUMEN
The expression of leptin and leptin receptor (Ob-R) has been partially elucidated in colon of patients with inflammatory bowel diseases (IBDs), even though leptin is involved in angiogenesis and inflammation. We previously reported overexpression of GLUT5 fructose transporter, in aberrant clusters of lymphatic vessels in lamina propria of IBD and controls. Here, we examine leptin and Ob-R expression in the same biopsies. Specimens were obtained from patients with ulcerative colitis (UC), Crohn's disease (CD) and controls who underwent screening for colorectal cancer, follow-up after polypectomy or with a history of lower gastrointestinal symptoms. Immunohistochemistry revealed leptin in apical and basolateral membranes of short epithelial portions, Ob-R on the apical pole of epithelial cells. Leptin and Ob-R were also identified in structures and cells scattered in the lamina propria. In UC, a significant correlation between leptin and Ob-R in the lamina propria was found in all inflamed samples, beyond non-inflamed samples of the proximal tract, while in CD, it was found in inflamed distal samples. Most of the leptin and Ob-R positive areas in the lamina propria were also GLUT5 immunoreactive in inflamed and non-inflamed mucosa. A significant correlation of leptin or Ob-R expression with GLUT5 was observed in the inflamed distal samples from UC. Our findings suggest that there are different sites of leptin and Ob-R expression in large intestine and those in lamina propria do not reflect the status of mucosal inflammation. The co-localization of leptin and/or Ob-R with GLUT5 may indicate concomitance effects in colorectal lamina propria areas.
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Colitis Ulcerosa/inmunología , Colon/inmunología , Enfermedad de Crohn/inmunología , Mucosa Intestinal/inmunología , Leptina/inmunología , Receptores de Leptina/inmunología , Adulto , Estudios de Casos y Controles , Colon/citología , Femenino , Transportador de Glucosa de Tipo 5/inmunología , Humanos , Mucosa Intestinal/citología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Adipokines (APN) are mainly secreted by adipocytes, macrophages and various other cells, along with their role in the regulation and mediation of inflammatory responses. APN is almost exclusively synthesized by adipocytes and regulated by peroxisome proliferator-activated receptor γ (PPARγ) that is involved in the epithelial-mesenchymal transition, linked lung fibrosis. Leptin is involved in acute lung injury with a role in lung fibrogenesis. Little is known about the relationship between APN/leptin and idiopathic pulmonary fibrosis (IPF) and the few studies available in the literature used ELISA to detect these lipid mediators. Our study is also the first to measure adipokines by the new multiplex assay and for the first time were performed in bronchoalveolar lavage (BAL) from IPF patients. This preliminary study suggests that APN levels in serum could be useful for predicting the prognosis of IPF, as they are inversely correlated with DLco percentages and BMI. Moreover, this first analysis of APN in BAL from IPF patients by a new method demonstrated an inverse correlation between these levels and BMI values and a direct correlation with eosinophil percentages, both of which are negative prognostic factors of IPF.
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Adiponectina/sangre , Líquido del Lavado Bronquioalveolar/química , Fibrosis Pulmonar Idiopática/sangre , Leptina/sangre , Adiponectina/inmunología , Anciano , Bioensayo , Índice de Masa Corporal , Líquido del Lavado Bronquioalveolar/inmunología , Femenino , Humanos , Fibrosis Pulmonar Idiopática/inmunología , Leptina/inmunología , Masculino , Persona de Mediana EdadRESUMEN
Overweight and obesity are major risk factors for diabetes, cardiovascular disease, and lung disease. These diseases are the most commonly reported health conditions that predispose individuals with SARS-CoV-2 infection to require hospitalization including intensive care unit admissions. The innate immune response is the host's first line of defense against a human coronavirus infection. However, most coronaviruses are armed with one strategy or another to overcome host antiviral defense, and the pathogenicity of the virus is related to its capacity to suppress host immunity. The multifaceted nature of obesity including its effects on immunity can fundamentally alter the pathogenesis of acute respiratory distress syndrome and pneumonia, which are the major causes of death due to SARS-CoV-2 infection. Elevated circulating leptin concentrations are a hallmark of obesity, which is associated with a leptin-resistant state. Leptin is secreted by adipocytes in proportion to body fat and regulates appetite and metabolism through signaling in the hypothalamus. However, leptin also signals through the Jak/STAT and Akt pathways, among others, to modulate T cell number and function. Thus, leptin connects metabolism with the immune response. Therefore, it seems appropriate that its dysregulation would have serious consequences during an infection. We propose that leptin may be the link between obesity and its high prevalence as a comorbidity of the SARS-CoV-2 infection. In this article, we present a synthesis of the mechanisms underpinning susceptibility to respiratory viral infections and the contribution of the immunomodulatory effects of obesity to the outcome.
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Infecciones por Coronavirus , Leptina , Obesidad , Pandemias , Neumonía Viral , Betacoronavirus , COVID-19 , Comorbilidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/metabolismo , Interacciones Huésped-Patógeno/inmunología , Humanos , Leptina/sangre , Leptina/inmunología , Leptina/metabolismo , Obesidad/epidemiología , Obesidad/inmunología , Obesidad/metabolismo , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Neumonía Viral/metabolismo , SARS-CoV-2 , Transducción de Señal/inmunologíaRESUMEN
The severity of coronavirus disease 2019 (COVID-19) infection is quite variable and the manifestations varies from asymptomatic disease to severe acute respiratory infection. Fever, dry cough, dyspnea, myalgia, fatigue, loss of appetite, olfactory and gustatory dysfunctions are the most prevalent general symptoms. Decreased immune system cells such as suppressed regulatory T cells, cytotoxic and helper T cells, natural killer cells, monocytes/macrophages and increased proinflammatory cytokines are the characteristic features. Compounds derived from Allium sativum (garlic) have the potential to decrease the expression of proinflammatory cytokines and to reverse the immunological abnormalities to more acceptable levels. Allium sativum is suggested as a beneficial preventive measure before being infected with SARS-CoV-2 virus. Allium sativum is a functional food well-known for its immunomodulatory, antimicrobial, antiinflammatory, antimutagenic, antitumor properties. Its antiviral efficiency was also demonstrated. Some constituents of this plant were found to be active against protozoan parasites. Within this context, it appears to reverse most immune system dysfunctions observed in patients with COVID-19 infection. The relations among immune system parameters, leptin, leptin receptor, adenosin mono phosphate-activated protein kinase, peroxisome proliferator activated receptor-gamma have also been interpreted. Leptin's role in boosting proinflammatory cytokines and in appetite decreasing suggest the possible beneficial effect of decreasing the concentration of this proinflammatory adipose tissue hormone in relieving some symptoms detected during COVID-19 infection. In conclusion, Allium sativum may be an acceptable preventive measure against COVID-19 infection to boost immune system cells and to repress the production and secretion of proinflammatory cytokines as well as an adipose tissue derived hormone leptin having the proinflammatory nature.
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COVID-19/dietoterapia , COVID-19/inmunología , Alimentos Funcionales , Ajo , COVID-19/virología , Interacciones Microbiota-Huesped/inmunología , Humanos , Leptina/inmunología , Modelos Inmunológicos , SARS-CoV-2/inmunología , Linfocitos T/inmunologíaRESUMEN
OBJECTIVES: Our study aimed to explore the relationship between leptin and IFN-γ in PCOS patients, and confirmed the effect of leptin-induced IFN-γ on granulosa cells furtherly. METHODS: 29 patients with PCOS and 36 healthy controls were enrolled. Leptin level and the proportion of Th1 cells were detected and association between them were analyzed. Meanwhile, peripheral blood mononuclear cells (PBMCs) isolated from PCOS patients were treated with leptin and then the proportion of Th1 was analyzed. Besides that, the apoptotic level of KGN cells was monitored after IFN-γ treatment. RESULTS: In the circulation of PCOS patients, leptin level dramatically increased compared with controls. And, this was associated with upregulated Th1 cells proportion and IFN-γ level. In vitro, Th1 cells proportion increased after leptin treated PBMCs from PCOS patients. Furthermore, for KGN cells, the percentage of live cells decreased and later apoptosis cells increased after IFN-γ treatment. CONCLUSIONS: Our results indicated that leptin takes part in process of PCOS via inducing expression of IFN-γ. Our findings highlight the importance of the connection between leptin and inflammation in PCOS and provide new insights therapeutic strategy for this disease.
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Apoptosis/inmunología , Células de la Granulosa/metabolismo , Interferón gamma/inmunología , Leptina/inmunología , Síndrome del Ovario Poliquístico/inmunología , Células TH1/inmunología , Adulto , Apoptosis/genética , Estudios de Casos y Controles , Línea Celular Tumoral , Femenino , Hormona Folículo Estimulante/sangre , Células de la Granulosa/efectos de los fármacos , Humanos , Técnicas In Vitro , Inflamación/sangre , Inflamación/inmunología , Interferón gamma/sangre , Interferón gamma/farmacología , Leptina/sangre , Leptina/genética , Leptina/farmacología , Leucocitos Mononucleares , Hormona Luteinizante/sangre , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/genética , Prolactina/sangre , Receptores de Leptina/genética , Receptores de Leptina/inmunología , Testosterona/sangreRESUMEN
Leptin-based obesity pharmacotherapies were originally developed according to the lipostatic view that elevated circulating leptin levels promote a negative energy balance. A series of independent preclinical findings suggest, however, that a partial reduction in circulating leptin levels (either by immunoneutralization, a peripherally restricted CB1 receptor inverse agonist, or bariatric surgery) can paradoxically lead to weight loss.
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Anticuerpos Neutralizantes/farmacología , Cirugía Bariátrica , Agonistas de Receptores de Cannabinoides/farmacología , Leptina/sangre , Obesidad/sangre , Obesidad/terapia , Receptor Cannabinoide CB1/agonistas , Animales , Leptina/inmunología , Obesidad/tratamiento farmacológicoRESUMEN
Leptin is a critical mediator of the immune response to changes in overall nutrition. Leptin is produced by adipocytes in proportion to adipose tissue mass and is therefore increased in obesity. Despite having a well-described role in regulating systemic metabolism and appetite, leptin displays pleiotropic actions, and it is now clear that leptin has a key role in influencing immune cell function. Indeed, many immune cells have been shown to respond to leptin directly via the leptin receptor, resulting in a largely pro-inflammatory phenotype. Understanding the role of adipose-tissue derived mediators in inflammation is critical to determining the pathophysiology of multiple obesity-associated diseases, such as type 2 diabetes, autoimmune disease, and infection. This review, therefore, focuses on the latest data regarding the role of leptin in modulating inflammation.
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Tejido Adiposo/inmunología , Enfermedades Autoinmunes/inmunología , Diabetes Mellitus Tipo 2/inmunología , Infecciones/inmunología , Leptina/inmunología , Obesidad/inmunología , Humanos , Receptores de Leptina/inmunologíaRESUMEN
Leptin is the forerunner of the adipokine superfamily and plays a key role in regulating energy expenditure and neuroendocrine function. Researches into leptin put emphasize not only on the metabolic role but also its immunoregulatory effect on immune response through immunocyte activation and cytokine secretion. Leptin acts on receptors that are widespread throughout the body and that are expressed across many tissue types. As a consequence, the abnormal expression of leptin has been found to correlate with a number of diseases, including cancers, autoimmune diseases, and cardiovascular diseases. The significance of leptin in the development of autoimmune diseases is becoming increasingly prominent. Systemic lupus erythematosus (SLE) is a severe atypical autoimmune disease that causes damage to multiple organ systems. It is characterised by the following: impaired clearance of apoptotic cells, loss of tolerance to self-antigens, aberrant activation of T cells and B cells, and chronic inflammation. The heightened immunocyte response in SLE means that these physiological systems are particularly vulnerable to regulation by leptin in addition to being of great significance to the research field. Our current review provides insight into the regulatory roles that leptin plays on immune effector cells in SLE.
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Linfocitos B/inmunología , Citocinas/inmunología , Leptina/inmunología , Lupus Eritematoso Sistémico/inmunología , Macrófagos/inmunología , Neutrófilos/inmunología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Humanos , Inflamación/inmunologíaRESUMEN
Obesity has become a world-wide pandemic and is considered a major risk factor for various diseases. Despite this, recent intriguing clinical observations have been made suggesting that being overweight has some advantages. Overweight and some obese patients were reported to have significantly lower all-cause mortality, described as the 'obesity paradox'. This phenomenon resulted in increased research aimed at investigating the influence of adipose tissue on outcomes of various clinical states including critical illness. In this review, we summarise research findings on the effect burn injury and trauma-related critical illness have on adipose tissue and discuss potential mechanisms by which adipose tissue influences outcomes in burn and other critically ill patients. Burn injury and critical illness influence adipose tissue functionally and morphologically, with circulating levels of fat derived hormones, adipokines, altered in patients following injury and/or critical illness. As adipokines regulate a variety of processes including inflammation and metabolism, this disruption in the adipokine axis may explain the obesity paradox phenomenon observed in critically ill patients. We conclude that further research on the influence of individual adipokines on prognosis in burn and critically ill patients and the mechanisms involved is required to increase understanding of their therapeutic potential.
Asunto(s)
Adipoquinas/metabolismo , Tejido Adiposo/metabolismo , Quemaduras/metabolismo , Obesidad/metabolismo , Adipoquinas/inmunología , Adiponectina/inmunología , Adiponectina/metabolismo , Tejido Adiposo/inmunología , Quemaduras/inmunología , Enfermedad Crítica , Fibrosis/inmunología , Fibrosis/metabolismo , Ghrelina/inmunología , Ghrelina/metabolismo , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Leptina/inmunología , Leptina/metabolismo , Nicotinamida Fosforribosiltransferasa/inmunología , Nicotinamida Fosforribosiltransferasa/metabolismo , Obesidad/inmunología , Sobrepeso/inmunología , Sobrepeso/metabolismo , Resistina/inmunología , Resistina/metabolismo , Piel/inmunología , Piel/metabolismo , Cicatrización de Heridas/inmunología , Cicatrización de Heridas/fisiologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal properties of grapes (Vitis vinifera L.) are well known since ancient times. Ethnobotanical grape preparations, like the Ayurvedic Darakchasava are used as cardiotonic and for the treatment of cardiovascular diseases. Dried grape products are also applied in Iranian traditional medicine for memory problems, which are linked to the pathology of brain microvessels, a special part of the cardiovascular system. The anti-inflammatory and protective effects of these traditional preparations on the cardiovascular system are related to their bioactive phenolic compounds. AIM OF THE STUDY: The blood-brain barrier (BBB), formed by brain capillaries, is not only involved in inflammatory and other diseases of the central nervous system, but also in many systemic diseases with an inflammatory component. Dietary obesity is a systemic chronic inflammatory condition in which the peripheral and central vascular system is affected. Among the cerebrovascular changes in obesity defective leptin transport across the BBB related to central leptin resistance is observed. Our aim was to study the protective effects of grape phenolic compounds epicatechin (EC), gallic acid (GA) and resveratrol (RSV) and grape-seed proanthocyanidin-rich extract (GSPE) on a cytokine-induced vascular endothelial inflammation model. Using a culture model of the BBB we investigated cytokine-induced endothelial damage and changes in the expression of leptin receptors and leptin transfer. MATERIALS AND METHODS: For the BBB model, primary cultures of rat brain endothelial cells, glial cells and pericytes were used in co-culture. Cells were treated by tumor necrosis factor-α (TNF-α) and interleukin-1 ß (IL-1ß) (10â¯ng/ml each) to induce damage. Cell toxicity was evaluated by the measurement of impedance. The expression of leptin receptors was assessed by RT-qPCR and western blot. The production of reactive oxygen species (ROS) and nitric oxide (NO) were detected by fluorescent probes. RESULTS: GSPE (10⯵g/ml), EC (10⯵M), GA (1⯵M) or RSV (10⯵M) did not change the viability of brain endothelial cells. The gene expression of the short leptin receptor isoform, Ob-Ra, was up-regulated by GSPE, EC and RSV, while the mRNA levels of Lrp2 and clusterin, clu/ApoJ were not affected. The tested compounds did not change the expression of the long leptin receptor isoform, Ob-Rb. RSV protected against the cytokine-induced increase in albumin permeability of the BBB model. GSPE and EC exerted an antioxidant effect and GSPE increased NO both alone and in the presence of cytokines. The cytokine-induced nuclear translocation of transcription factor NF-κB was blocked by GSPE, GA and RSV. Cytokines increased the mRNA expression of Lrp2 which was inhibited by EC. RSV increased Ob-Ra and Clu in the presence of cytokines. Cytokines elevated leptin transfer across the BBB model, which was not modified by GSPE or RSV. CONCLUSION: Our results obtained on cell culture models confirm that natural grape compounds protect vascular endothelial cells against inflammatory damage in accordance with the ethnopharmacological use of grape preparations in cardiovascular diseases. Furthermore, grape compounds and GSPE, by exerting a beneficial effect on the BBB, may also be considered in the treatment of obesity after validation in clinical trials.
Asunto(s)
Barrera Hematoencefálica/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Extracto de Semillas de Uva/farmacología , Inflamación/tratamiento farmacológico , Proantocianidinas/farmacología , Vitis/química , Animales , Animales Recién Nacidos , Astrocitos , Barrera Hematoencefálica/citología , Barrera Hematoencefálica/inmunología , Catequina/farmacología , Células Cultivadas , Citocinas/inmunología , Evaluación Preclínica de Medicamentos , Células Endoteliales/inmunología , Células Endoteliales/patología , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/inmunología , Etnofarmacología , Ácido Gálico/farmacología , Extracto de Semillas de Uva/química , Extracto de Semillas de Uva/uso terapéutico , Humanos , Inflamación/inmunología , Inflamación/patología , Leptina/inmunología , Leptina/metabolismo , Medicina Ayurvédica/métodos , Cultivo Primario de Células , Proantocianidinas/química , Proantocianidinas/uso terapéutico , Ratas , Especies Reactivas de Oxígeno/metabolismo , Receptores de Leptina/metabolismo , Resveratrol/farmacologíaRESUMEN
Las proteínas participan en el resguardo del estado fisiológico de los tejidos buco-dentales, contribuyendo en la protección y recuperación de los mismos. En el caso de la leptileptina, una citoquina tipo I reconocida por regular la ingesta de alimentos y el gasto energético, la evidencia actual señala además su rol en la inmunidad e inflamación, induciendo la producción de otras citoquinas y estimular la fagocitosis. Siendo la enfermedad periodontal la segunda patología bucodental más prevalente en el mundo, caracterizada por inflamación crónica, inducida por bacterias periodontopatógenas, es necesario conocer los elementos biológicos que participan en la patogenia de la misma. La siguiente revisión bibliográfica tiene como propósito discernir la participación de la leptina en la enfermedad periodontal. En el periodonto la leptina participa exhibiendo un comportamiento protector, donde la disminución de los niveles del péptido en encía, fluido crevicular gingival (FCG) y saliva, es inversamente proporcional al grado de severidad de la enfermedad periodontal; permitiendo considerar que la valoración de leptina en FCG puede ser empleada como herramienta de diagnóstico y pronóstico de las alteraciones periodontales
Proteins participate in the protection of the physiological state of the oral tissues, contributing in the protection and recovery of them. In the case of leptin, a type I cytokine, recognized for regulating food intake and energy expenditure, current evidence also points to its role in immunity and inflammation, inducing the production of other cytokines and stimulating phagocytosis. Being the periodontal disease the second most prevalent oral pathology in the world, characterized by chronic inflammation, induced by periodontopathogenic bacteria, it is necessary to know the biological elements that participate in the pathogenesis of it. The purpose of the following literature review is to discern the participation of leptin in periodontal disease. In the periodontium leptin participates exhibiting a protective behavior, where the decrease in the levels of the peptide in the gingiva, gingival crevicular fluid (FCG) and saliva, is inversely proportional to the degree of severity of the periodontal disease; allowing to consider that the evaluation of leptin in FCG can be used as a tool for diagnosis and prognosis of periodontal alterations
Asunto(s)
Humanos , Enfermedades Periodontales/tratamiento farmacológico , Leptina/uso terapéutico , Leptina/inmunología , Leptina/metabolismo , Gingivitis/tratamiento farmacológico , Líquido del Surco Gingival/efectos de los fármacosRESUMEN
: Worldwide, breast cancer (BC) is the most common malignancy in women, in regard to incidence and mortality. In recent years, the negative role of obesity during BC development and progression has been made abundantly clear in several studies. However, the distribution of body fat may be more important to analyze than the overall body weight. In our review of literature, we reported some key findings regarding the role of obesity in BC development, but focused more on central adiposity. Firstly, the adipose microenvironment in obese people bears many similarities with the tumor microenvironment, in respect to associated cellular composition, chronic low-grade inflammation, and high ratio of reactive oxygen species to antioxidants. Secondly, the adipose tissue functions as an endocrine organ, which in obese people produces a high level of tumor-promoting hormones, such as leptin and estrogen, and a low level of the tumor suppressor hormone, adiponectin. As follows, in BC this leads to the activation of oncogenic signaling pathways: NFκB, JAK, STAT3, AKT. Moreover, overall obesity, but especially central obesity, promotes a systemic and local low grade chronic inflammation that further stimulates the increase of tumor-promoting oxidative stress. Lastly, there is a constant exchange of information between BC cells and adipocytes, mediated especially by extracellular vesicles, and which changes the transcription profile of both cell types to an oncogenic one with the help of regulatory non-coding RNAs.