RESUMEN
PURPOSE: Limited epidemiologic data are available on the expression of adipokines leptin (LEP) and adiponectin (ADIPOQ) and adipokine receptors (LEPR, ADIPOR1, ADIPOR2) in the breast tumor microenvironment (TME). The associations of gene expression of these biomarkers with tumor clinicopathology are not well understood. METHODS: NanoString multiplexed assays were used to assess the gene expression levels of LEP, LEPR, ADIPOQ, ADIPOR1, and ADIPOR2 within tumor tissues among 162 Black and 55 White women with newly diagnosed breast cancer. Multivariate mixed effects models were used to estimate associations of gene expression with breast tumor clinicopathology (overall and separately among Blacks). RESULTS: Black race was associated with lower gene expression of LEPR (P = 0.002) and ADIPOR1 (P = 0.01). Lower LEP, LEPR, and ADIPOQ gene expression were associated with higher tumor grade (P = 0.0007, P < 0.0001, and P < 0.0001, respectively) and larger tumor size (P < 0.0001, P = 0.0005, and P < 0.0001, respectively). Lower ADIPOQ expression was associated with ER- status (P = 0.0005), and HER2-enriched (HER2-E; P = 0.0003) and triple-negative (TN; P = 0.002) subtypes. Lower ADIPOR2 expression was associated with Ki67+ status (P = 0.0002), ER- status (P < 0.0001), PR- status (P < 0.0001), and TN subtype (P = 0.0002). Associations of lower adipokine and adipokine receptor gene expression with ER-, HER2-E, and TN subtypes were confirmed using data from The Cancer Genome Atlas (P-values < 0.005). CONCLUSION: These findings suggest that lower expression of ADIPOQ, ADIPOR2, LEP, and LEPR in the breast TME might be indicators of more aggressive breast cancer phenotypes. Validation of these findings are warranted to elucidate the role of the adipokines and adipokine receptors in long-term breast cancer prognosis.
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Neoplasias de la Mama , Receptores de Adipoquina , Adipoquinas/genética , Adiponectina/genética , Neoplasias de la Mama/genética , Femenino , Expresión Génica , Humanos , Polimorfismo de Nucleótido Simple , Receptores de Leptina/genética , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: The role of ADIPOQ gene rs266729 variants on weight loss after a dietary intervention are still unclear. OBJECTIVE: To analyze the effects of the ADIPOQ gene rs266729 variant n weight loss, cardiovascular risk factors, and adiponectin levels after two hypocaloric diets with different dietary fatty profiles. DESIGN: A population of 362 obese patients was enrolled in a randomized clinical trial with two diets (Diet M, monounsaturated fat-enriched diet, and Diet P, polyunsaturated-fat enriched diet). Anthropometric measurements, an assessment of nutritional intake, and biochemical tests were performed at baseline and after 12 weeks. RESULTS: Weight loss was similar with both diets. After Diet M, only subjects with CC genotype showed significant improvements in total cholesterol (CC vs. CG ± GG) -9.0 ±1.1 mU/L vs. -4.5 ± 2.4 mg/dL, p = 0.01), LDL cholesterol (-6.0 ± 1.1 mg/dL vs. -3.0 ± 0.9 mg/dL, p = 0.03), glucose (-4.7 ± 1.1 mg/dL vs. -0.6 ± 0.5 mg/dL, p = 0.01), and insulin levels (-2.6 ±1.0 mU/L vs. -0.7 ± 0.3 mU/L, p = 0.02) and in HOMA-IR (-0.5 ± 0.2 units vs. -0.2 ± 0.4 units, p = 0.03). The same improvement was reported after Diet P in all parameters, including total cholesterol (CC vs. CG±GG) (-8.0 ± 1.2mU/L vs. -2.1 ± 1.4 mg/dL, p = 0.02), LDL cholesterol (-7.3 ± 1.2 mg/dL vs. -2.1 ± 0.8 mg/dL, p = 0.02), glucose (-3.2 ± 0.1mg/dL vs. -0.2 ± 0.5 mg/dL, p = 0.01), and insulin levels (-2.5 ± 1.0 mU/L vs. -1 ± 0.6 mU/L, p = 0.02) and HOMA-IR (-0.5 ± 0.1 units vs. −0.3 ± 0.4 units, p = 0.02). Only subjects with CC genotype showed significant increases in adiponectin levels after both diets: (Diet M: 10.3 ± 2.0 ng/dL vs. Diet P: 9.3 ± 2.9 ng/dL, p = 0.43). CONCLUSION: The CC genotype of ADIPOQ gene rs266729 variant is associated to increased adiponectin levels and decreases in LDL cholesterol, glucose, insulin, and HOMA-IR levels after weight loss
ANTECEDENTES: El papel de las variantes del gen ADIPOQ en la pérdida de peso después de una intervención dietética sigue sin estar claro. OBJETIVO: Nuestro objetivo fue analizar los efectos de la variante rs266729 del gen ADIPOQ sobre la pérdida de peso, los factores de riesgo cardiovascular y los niveles de adiponectina después de 2 dietas hipocalóricas con diferentes perfiles de grasas en la dieta. DISEÑO: Una población de 362 pacientes obesos se incluyeron en un ensayo clínico aleatorizado con 2 dietas (dieta M: dieta enriquecida con grasas monoinsaturadas y dieta P: dieta enriquecida con grasas poliinsaturadas). Antes y tras 12 semanas, se realizó una evaluación antropométrica, evaluación de la ingesta nutricional y un análisis bioquímico. RESULTADOS: La pérdida de peso fue similar con ambas dietas. Después de la dieta M, solo los sujetos con genotipo CC mostraron una mejoría significativa en el colesterol total (CC vs. CG±GG) (-9,0 ± 1,1 mU/l vs. - 4,5 ± 2,4 mg/dl; p = 0,01), colesterol LDL (-6,0 ± 1,1 mg/dl vs. - 3,0 ± 0,9 mg/dl; p = 0,03), glucosa (-4,7 ± 1,1 mg/dl vs. -0,6 ± 0,5 mg/dl; p = 0,01), niveles de insulina (-2,6 ± 1,0 mU/l vs. -0,7± 0,3 mU/l; p = 0,02) y HOMA-IR (- 0,5 ± 0,2 unidades vs. -0,2 ± 0,4 unidades; p = 0,03). La misma mejora en todos los parámetros se informó después de la dieta P; niveles de colesterol total (CC vs. CG ± GG) (-8,0 ± 1,2 mU/l vs. -2,1 ± 1,4 mg/dl; p = 0,02), colesterol LDL (-7,3 ± 1,2 mg/dl vs. -2,1 ±0,8 mg/dl; p = 0,02), glucosa (-3,2 ± 0,1 mg/dl vs. -0,2 ± 0,5 mg/dl; p = 0,01), niveles de insulina (-2,5 ±1,0 mU/l vs. -1 ±0,6 mU/l; p = 0,02) y HOMA-IR (-0,5 ± 0,1 unidades vs. -0,3 ± 0,4 unidades; p = 0,02). Solo los sujetos con genotipo CC mostraron un aumento significativo de los niveles de adiponectina después de ambas dietas: (dieta M: 10,3 ± 2,0 ng/dl vs. dieta P: 9,3 ± 2,9 ng/dl; p = 0,43). CONCLUSIÓN: El genotipo CC de la variante rs266729 del gen ADIPOQ se asocia con aumentos en los niveles de adiponectina y disminución del colesterol LDL, glucosa, insulina y HOMA-IR tras la pérdida de peso
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Humanos , Ácidos Grasos/sangre , Adiponectina/genética , Dieta Reductora/métodos , Pérdida de Peso , Grasas de la Dieta/uso terapéutico , Adiponectina/sangre , Obesidad/dietoterapia , Antropometría , LDL-Colesterol , Genotipo , Estudios Prospectivos , Adiponectina/metabolismo , Receptores de Adipoquina/sangre , Análisis de VarianzaRESUMEN
Cell polarity is crucial for the correct structural and functional organization of epithelial tissue. Its disruption can lead to loss of the apicobasal polarity, alteration in the intracellular components, misregulation of the pathways involved in cell proliferation and cancer promotion. Very recent in vitro/in vivo findings demonstrated that obesity-associated alterations in tissue adipokines protein level negatively affect epithelial polarity. We performed an in silico study to investigate whether such alterations also occur in surgical samples. We aimed to explore the relationship among the expression of the genes coding for leptin (LEP), adiponectin (ADIPOQ), adipokine receptors (LEPR, ADIPOR1 and ADIPOR2), and a panel of polarity-associated genes in normal tissue from breast reduction mammoplasty, and a series of paired samples of histologically normal (HN) tissue and invasive cancer. Results indicated that, in normal tissue, the expression of adipokines and their receptors negatively correlated with that of the polarity-associated genes and GGT1, which codes for γ-glutamyl transferase (GGT) enzyme, a marker of cell distress and membrane disruption. This negative correlation progressively decreased in HN and cancerous tissue, and loss of correlation between ADIPOR2 and polarity-associated genes appeared the most noticeable alteration. Given the growing role of obesity in breast cancer etiology and the opposite action of leptin and adiponectin in epithelial tissue remodeling, ADIPOR2 loss could be addressed as a key mechanism leading to an unbalanced leptin stimulatory activity, subsequent cell polarity disruption and eventually tumor initiation, a finding that requires to be confirmed also at the protein level and with in vivo models.
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Adipoquinas/genética , Neoplasias de la Mama/genética , Mama/metabolismo , Mama/patología , Polaridad Celular/genética , Regulación Neoplásica de la Expresión Génica , Adiponectina/genética , Mama/cirugía , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Simulación por Computador , Células Epiteliales/metabolismo , Células Epiteliales/patología , Femenino , Humanos , Leptina/genética , Mamoplastia , Receptores de Adipoquina/genética , Receptores de Leptina/genética , Transcriptoma , gamma-Glutamiltransferasa/genéticaRESUMEN
INTRODUCTION: the composition of snack foods likely influences the overall effect that snacking has on metabolism and obesity. The objective of the current study was to assess the responses to two different snacks, one of them supplemented with wakame and carobs, on cardiovascular risk factors, satiety, and subsequent food intake in obese subjects with metabolic syndrome. MATERIAL AND METHODS: forty patients were randomized in a clinical trial (NCT03420989, clinicaltrial.gov) to group I (enriched snack, n = 16) or group II (control snack, n = 16). At baseline and after 8 weeks biochemical parameters, dietary intakes, and nutritional status were assessed. The subjects also rated their feelings of satiety/hunger with a test meal. RESULTS: no differences were detected in anthropometric parameters between both snacks. Changes in other parameters were detected in patients with enriched snacks, with a significant decrease in LDL-cholesterol by 7.4 % (intervention snack, -8.9 ± 2.3 mg/dL vs control snack, -0.9 ± 3.3 mg/dL; p = 0.03), in total cholesterol by 5.8 % (intervention snack, -10.4 ± 2.9 mg/dL vs control snack, -1.4 ± 3.2 mg/dL; p = 0.02), and in resistin level by 15.9 % (intervention snack, -1.0 ± 0.2 mg/dL vs control snack, -0.1 ± 0.3 mg/dL: p = 0.03). After the test meal, satiety scores (after 20 min and 40 min) were higher than fasting levels in both groups. The same results were obtained with the 100-mm, 5-point visual satiety scale. CONCLUSION: our study indicates that a wakame- and carob-enriched snack induces a significant decrease in total cholesterol, LDL-cholesterol, and resistin levels when compared to a control snack, without effects on food consumption, other cardiovascular parameters, or anthropometric parameters
INTRODUCCIÓN: la composición de los "snacks" probablemente influya en el efecto que produce su consumo sobre los marcadores metabólicos y la obesidad. El objetivo del presente estudio fue evaluar las respuestas a dos snacks, uno de ellos suplementado con wakame y algarroba, sobre factores de riesgo cardiovascular, saciedad y posterior ingesta de alimentos, en sujetos obesos con síndrome metabólico. MATERIAL Y MÉTODOS: se aleatorizaron 40 pacientes en el ensayo clínico NCT03420989 (clinicaltrial.gov) para participar en el grupo I (snack enriquecido, n = 16) o el grupo II (snack de control, n = 16). Antes y después de 8 semanas se determinaron los parámetros bioquímicos, las ingestas dietéticas y el estado nutricional. A los sujetos también se les evaluó la saciedad y el apetito con una comida de prueba. RESULTADOS: no se detectaron diferencias en los parámetros antropométricos con ambos snacks. Se detectaron cambios en los parámetros bioquímicos de los pacientes que recibieron snacks enriquecidos, con una disminución significativa del colesterol-LDL del 7,4 % (snack de intervención, -8,9 ± 2,3 mg/dl vs. snack de control, -0,9 ± 3,3 mg/dl; p = 0,03), del colesterol total del 5,8 % (snack de intervención, -10,4 ± 2,9 mg/dl vs. snack de control, -1,4 ± 3,2 mg/dl; p = 0,02) y de los niveles de resistina del 15,9 % (snack de intervención, -1,0 ± 0,2 mg/dl vs. snack de control, -0,1 ± 0,3 mg/dl; p = 0,03). Después de la comida de prueba, las puntuaciones de saciedad (a los 20 min y 40 min) fueron más altas que el nivel de ayuno en ambos grupos. Los resultados fueron similares con la escala de saciedad visual de 5 puntos y 100 mm. CONCLUSIÓN: nuestro estudio muestra que un snack enriquecido con wakame y algarroba produce una disminución significativa de los niveles de colesterol total, colesterol-LDL y resistina frente a un snack de control, sin efectos sobre el consumo de alimentos, otros parámetros cardiovasculares y los parámetros antropométricos
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Bocadillos/fisiología , Ingestión de Energía/fisiología , Undaria , Método Doble Ciego , Obesidad/dietoterapia , Extractos Vegetales/farmacología , Factores de Riesgo , Enfermedades Cardiovasculares/prevención & control , Síndrome Metabólico/dietoterapia , LDL-Colesterol/metabolismo , Antropometría , Receptores de Adipoquina/administración & dosificación , Undaria/química , Galactanos/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
In broiler hens, the genetic selection increased susceptibility to metabolic disorders and reproductive dysfunctions. In human ovarian cells, grape seed extracts (GSE) improved steroid production. Here, we investigated the effects of a GSE dietary supplementation on egg production and quality, fertility parameters, Reactive Oxygen Species (ROS) and steroid content in yolk egg associated to plasma adipokines in broiler hens. For this, we designed two in vivo experiments, the first one included three groups of hens: A (control), B and C (supplemented with GSE at 0.5% and 1% of the total diet composition, respectively, since week 4), and the second one used two groups of hens: A (control) and D (supplemented with GSE at 1% of the total diet composition since hatching). We assessed the egg production from 23th to 40th weeks and quality at 33th week. After artificial inseminations, the fertility parameters were calculated. In egg yolk, Reactive Oxygen Species (ROS) level and steroid production were evaluated by Ros-Glo H202 and ELISA assay, respectively. Expression of steroidogenic enzymes and adipokines and their receptors was determined by RT-qPCR in ovarian cells and plasma adipokines (RARRES2, ADIPOQ and NAMPT) were evaluated by specific ELISA assays. The fertility parameters and egg production were unaffected by GSE supplementation whatever the experiment (exp.). However, the rate of double-yolk eggs decreased for all GSE supplemented groups (exp. 1 P <0.01, exp.2, P<0.02). In exp.1, C group eggs were bigger and larger (P<0.0001) and the shell elasticity was higher for both B and C (P<0.0003) as compared to control. In the egg yolk, GSE supplementation in both exp. reduced ROS content and steroidogenesis consistent with a decrease in P450 aromatase and StAR mRNA expression and basal in vitro progesterone secretion in granulosa cells (P<0.001). Interestingly, in both exp. RARRES2 plasma levels were positively correlated while ADIPOQ and NAMPT plasma levels were negatively correlated, with steroids and ROS in yolk (P<0.0001). Taken together, maternal dietary GSE supplementation did not affect egg production and fertility parameters whereas it reduced ROS content and steroidogenesis in yolk egg. Furthermore, it ameliorated egg quality by decreasing the number of double-yolk eggs and by improving the size of normal eggs and the elasticity of the shell. Taken together, our data suggest the possibility of using dietary maternal GSE to improve egg quality.
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Pollos/fisiología , Suplementos Dietéticos , Fertilidad/efectos de los fármacos , Extracto de Semillas de Uva/farmacología , Ovario/metabolismo , Óvulo/metabolismo , Reproducción/efectos de los fármacos , Esteroides/biosíntesis , Adipoquinas/sangre , Animales , Pollos/sangre , Pollos/genética , Dieta , Yema de Huevo/efectos de los fármacos , Yema de Huevo/metabolismo , Femenino , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Ovario/efectos de los fármacos , Oviposición/efectos de los fármacos , Óvulo/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores de Adipoquina/genética , Receptores de Adipoquina/metabolismo , Células Tecales/efectos de los fármacos , Células Tecales/metabolismoRESUMEN
BACKGROUND: The molecular mechanisms underlying the association between increased adiposity and aggressive breast cancer phenotypes remain unclear, but likely involve the adipokines, leptin (LEP) and adiponectin (ADIPOQ), and their receptors (LEPR, ADIPOR1, ADIPOR2). METHODS: We used immunohistochemistry (IHC) to assess LEP, LEPR, ADIPOQ, ADIPOR1, and ADIPOR2 expression in breast tumor tissue microarrays among a sample of 720 women recently diagnosed with breast cancer (540 of whom self-identified as Black). We scored IHC expression quantitatively, using digital pathology analysis. We abstracted data on tumor grade, tumor size, tumor stage, lymph node status, Ki67, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) from pathology records, and used ER, PR, and HER2 expression data to classify breast cancer subtype. We used multivariable mixed effects models to estimate associations of IHC expression with tumor clinicopathology, in the overall sample and separately among Blacks. RESULTS: Larger proportions of Black than White women were overweight or obese and had more aggressive tumor features. Older age, Black race, postmenopausal status, and higher body mass index were associated with higher LEPR IHC expression. In multivariable models, lower LEPR IHC expression was associated with ER-negative status and triple-negative subtype (P < 0.0001) in the overall sample and among Black women only. LEP, ADIPOQ, ADIPOR1, and ADIPOR2 IHC expression were not significantly associated with breast tumor clinicopathology. CONCLUSIONS: Lower LEPR IHC expression within the breast tumor microenvironment might contribute mechanistically to inter-individual variation in aggressive breast cancer clinicopathology, particularly ER-negative status and triple-negative subtype.
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Adipoquinas/metabolismo , Neoplasias de la Mama/metabolismo , Receptor alfa de Estrógeno/metabolismo , Receptores de Adipoquina/metabolismo , Receptores de Leptina/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Microambiente Tumoral , Adulto , Negro o Afroamericano/estadística & datos numéricos , Anciano , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Femenino , Humanos , Inmunohistoquímica/métodos , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias de la Mama Triple Negativas/clasificación , Neoplasias de la Mama Triple Negativas/patología , Adulto JovenRESUMEN
The mycotoxin zearalenone (ZEN), which frequently contaminates cereal-based human food and animal feed, is known to have an estrogenic effect. The biological response associated with exposure to ZEN has rarely been reported in organs other than the reproductive system. In the intestine, several studies suggested that ZEN might stimulate molecular changes related to the activation of early carcinogenesis, but the molecular mechanisms behind these events are not yet known. In this study, we investigated gene expression and changes in protein abundance induced by acute exposure to ZEN in the jejunum of castrated male pigs using an explant model. Our results indicate that ZEN induces the accumulation of ER but not ER, modulates Wnt/ß-catenin and TGF- signaling pathways, and induces molecular changes linked with energy sensing and the antimicrobial activity without inducing inflammation. Our results confirm that the intestine is a target for ZEN, inducing changes that promote cellular proliferation and could contribute to the onset of intestinal pathologies.
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Homeostasis/efectos de los fármacos , Yeyuno/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , Zearalenona/toxicidad , Alimentación Animal , Animales , Castración , Citocinas/genética , Citocinas/metabolismo , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Contaminación de Alimentos , Expresión Génica/efectos de los fármacos , Expresión Génica/inmunología , Homeostasis/genética , Homeostasis/inmunología , Yeyuno/inmunología , Yeyuno/metabolismo , Yeyuno/patología , Masculino , Receptores de Adipoquina/genética , Receptores de Adipoquina/metabolismo , Porcinos , Factores de Tiempo , Factor de Crecimiento Transformador beta/genética , Vía de Señalización Wnt/genética , Zearalenona/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
Gestational diabetes mellitus (GDM) is a disease of pregnancy associated with maternal and foetal hyperglycaemia and altered foetoplacental vascular function. Human foetoplacental microvascular and macrovascular endothelium from GDM pregnancy show increased maximal l-arginine transport capacity via the human cationic amino acid transporter 1 (hCAT-1) isoform and nitric oxide (NO) synthesis by the endothelial NO synthase (eNOS). These alterations are paralleled by lower maximal transport activity of the endogenous nucleoside adenosine via the human equilibrative nucleoside transporter 1 (hENT1) and activation of adenosine receptors. A causal relationship has been described for adenosine-activation of A2A adenosine receptors, hCAT-1, and eNOS activity (i.e. the Adenosine/l-Arginine/Nitric Oxide, ALANO, signalling pathway). Insulin restores these alterations in GDM via activation of insulin receptor A (IR-A) form in the macrovascular but IR-A and IR-B forms in the microcirculation of the human placenta. Adipokines are secreted from adipocytes influencing the foetoplacental metabolic and vascular function. Various adipokines are dysregulated in GDM, with adiponectin and leptin playing major roles. Abnormal plasma concentration of these adipokines and the activation or their receptors are involved in the pathophysiology of GDM. However, involvement of adipokines, adenosine, and insulin receptors and membrane transporters in the aetiology of this disease of pregnancy is unknown. This review focuses on the pathophysiology of insulin and adenosine receptors and l-arginine and adenosine membranes transporters giving an overview of the key adipokines leptin and adiponectin in the foetoplacental vasculature in GDM. This article is part of a Special Issue entitled: Membrane Transporters and Receptors in Pregnancy Metabolic Complications edited by Luis Sobrevia.
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Adenosina/metabolismo , Diabetes Gestacional/metabolismo , Endotelio Vascular/metabolismo , Insulina/metabolismo , Receptores de Adipoquina/metabolismo , Adipoquinas/sangre , Antígenos CD/metabolismo , Arginina/metabolismo , Transporte Biológico/fisiología , Transportador de Aminoácidos Catiónicos 1/metabolismo , Endotelio/metabolismo , Tranportador Equilibrativo 1 de Nucleósido/metabolismo , Femenino , Proteínas Activadoras de GTPasa , Humanos , Óxido Nítrico , Óxido Nítrico Sintasa de Tipo III/metabolismo , Placenta/metabolismo , Embarazo , Isoformas de Proteínas , Receptor de Insulina/metabolismo , Receptores Purinérgicos P1/metabolismo , Transducción de SeñalRESUMEN
In broiler chickens, the intense genetic selection for rapid growth has resulted in an increase in growth rate and fat deposition. Adipose tissue is now recognized as an important endocrine organ that secretes a variety of factors including adipokines. However, the expression pattern of these adipokines is unclear in chicken embryo development. In the present study, we determined the expression profile of three novel adipokines, NAMPT, RARRES2 and ADIPOQ, and their cognate receptors in metabolic tissues (liver, muscles and adipose tissue) of chicken embryo/chicks from 15â¯days of incubation (E15) to hatching (D0). From E15 to hatching, embryos gradually gained weight and started to develop subcutaneous adipose tissue at E15. We conducted western blot and RT-qPCR tests and found that ADIPOQ expression increased over time and was positively correlated with adipose tissue weight. In addition, NAMPT expression increased only in muscles. By using a new homemade chicken RARRES2 specific antibody we showed that RARRES2 protein levels increased specifically at hatching in adipose tissue, liver and pectoralis major and this was associated with an increase in the weight of embryo. Taken together, these results support a potential involvement of adipokines in metabolic regulation during chicken embryo development.
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Adipoquinas/genética , Tejido Adiposo/metabolismo , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Hígado/metabolismo , Músculos Pectorales/metabolismo , Adipoquinas/química , Adipoquinas/metabolismo , Secuencia de Aminoácidos , Animales , Proteínas Aviares/genética , Proteínas Aviares/metabolismo , Embrión de Pollo , Pollos/metabolismo , Tamaño de los Órganos , Óvulo/metabolismo , Receptores de Adipoquina/genética , Receptores de Adipoquina/metabolismoRESUMEN
BACKGROUND: Childhood obesity prevalence has increased worldwide and is an important risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). The production of inflammatory adipokines by obese adipose tissue contributes to the development of T2D and CVD. While levels of circulating adipokines such as adiponectin and leptin have been established in obese children and adults, the expression of adiponectin and leptin receptors on circulating immune cells can modulate adipokine signalling, but has not been studied so far. Here, we aim to establish the expression of adiponectin and leptin receptors on circulating immune cells in obese children pre and post-lifestyle intervention compared to normal weight control children. METHODS: 13 obese children before and after a 1-year lifestyle intervention were compared with an age and sex-matched normal weight control group of 15 children. Next to routine clinical and biochemical parameters, circulating adipokines were measured, and flow cytometric analysis of adiponectin receptor 1 and 2 (AdipoR1, AdipoR2) and leptin receptor expression on peripheral blood mononuclear cell subsets was performed. RESULTS: Obese children exhibited typical clinical and biochemical characteristics compared to controls, including a higher BMI-SD, blood pressure and circulating leptin levels, combined with a lower insulin sensitivity index (QUICKI). The 1-year lifestyle intervention resulted in stabilization of their BMI-SD. Overall, circulating leukocyte subsets showed distinct adipokine receptor expression profiles. While monocytes expressed high levels of all adipokine receptors, NK and iNKT cells predominantly expressed AdipoR2, and B-lymphocytes and CD4+ and CD8+ T-lymphocyte subsets expressed AdipoR2 as well as leptin receptor. Strikingly though, leukocyte subset numbers and adipokine receptor expression profiles were largely similar in obese children and controls. Obese children showed higher naïve B-cell numbers, and pre-intervention also higher numbers of immature transition B-cells and intermediate CD14++CD16+ monocytes combined with lower total monocyte numbers, compared to controls. Furthermore, adiponectin receptor 1 expression on nonclassical CD14+CD16++ monocytes was consistently upregulated in obese children pre-intervention, compared to controls. However, none of the differences in leukocyte subset numbers and adipokine receptor expression profiles between obese children and controls remained significant after multiple testing correction. CONCLUSIONS: First, the distinct adipokine receptor profiles of circulating leukocyte subsets may partly explain the differential impact of adipokines on leukocyte subsets. Second, the similarities in adipokine receptor expression profiles between obese children and normal weight controls suggest that adipokine signaling in childhood obesity is primarily modulated by circulating adipokine levels, instead of adipokine receptor expression.
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Leucocitos/citología , Obesidad/metabolismo , Receptores de Adipoquina/metabolismo , Adipoquinas/sangre , Adolescente , Índice de Masa Corporal , Estudios de Casos y Controles , Niño , Preescolar , Estudios de Cohortes , Femenino , Citometría de Flujo , Humanos , Masculino , Obesidad/sangreRESUMEN
No disponible
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Humanos , Estudios de Casos y Controles , Síndrome Metabólico/complicaciones , Síndrome Metabólico/tratamiento farmacológico , Receptores de Adipoquina/administración & dosificación , Sesgo de Selección , BiomarcadoresRESUMEN
Overweight is believed to be associated with colorectal cancer risk. Adipose tissue is loose connective tissue composed of adipocytes. It is now recognized as a major endocrine organ, secreting humoral factors collectively called adipokines. Aberrant hormonal systems consisting of modulated adipokines and their receptors are thought to play a role in colorectal carcinogenesis and cancer progression in obese conditions. However, it is still unclear whether and how each adipokine relates to colorectal carcinogenesis. Notably, a couple of molecules that were initially proposed to be obesity-related adipokines were disqualified by subsequent studies. The adipokines, adiponectin, and intelectin-1 (also known as omentin-1), whose levels are decreased in obesity, act as tumor suppressor factors in various cancers. Numerous studies have demonstrated a link between the insufficient expression and function of adiponectin and its receptor, T-cadherin, in colorectal carcinogenesis. Moreover, our recent study indicated that loss of TMEM207, which is critical for the proper processing of intelectin-1 in the colon mucosa, leads to insufficient intelectin-1 production, thus participating in colorectal carcinogenesis. Here, we discuss the recent understanding of the role of adipokines in colorectal carcinogenesis and subsequently describe the potent tumor suppressor roles of intelectin-1 and TMEM207 in colorectal cancer.
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Adiponectina/metabolismo , Transformación Celular Neoplásica/metabolismo , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/metabolismo , Citocinas/metabolismo , Lectinas/metabolismo , Obesidad/complicaciones , Obesidad/metabolismo , Adipoquinas/metabolismo , Animales , Proteínas Portadoras/metabolismo , Neoplasias Colorrectales/epidemiología , Proteínas Ligadas a GPI/metabolismo , Humanos , Leptina/metabolismo , Proteínas de la Membrana/metabolismo , Obesidad/epidemiología , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Sobrepeso/metabolismo , Receptores de Adipoquina/metabolismoRESUMEN
Background: The prevalence of obesity is increasing worldwide. Oxidative stress plays an etiological role in a variety of obesity-related metabolic disorders. 4-hydroxynonenal (4-HNE) is the most abundant and reactive aldehydic product derived from the peroxidation of n-6 polyunsaturated fatty acids with diverse biological effects that are not well detailed. Obesity is associated with decreased plasma adiponectin concentrations and increased production of lipid peroxidation products, including 4-HNE, in adipose tissue. There may be some association between the level of adipokines and 4-HNE. Material and methods: To analyze the associations between 4-HNE and classical adipokines, namely, adiponectin and leptin in a Chinese population, the plasma 4-HNE, adiponectin and leptin levels of 160 non-diabetic obese (NDO) patients and 160 healthy subjects were determined by ELISA, and their associations with adiposity, glucose, lipid profiles, insulin secretion and insulin sensitivity were studied. Results: Plasma 4-HNE levels were significantly increased in patients with NDO compared with healthy controls (p < 0.01). 4-HNE was negatively correlated with adiponectin and positively correlated with leptin. The plasma levels of 4-HNE were significantly correlated to several parameters involved in body mass index (BMI) and insulin resistance (IR). The 4-HNE levels were positively correlated with BMI and negatively correlated with insulin sensitivity. Conclusion: We conclude that 4-HNE is associated with the secretion of adiponectin and leptin and is correlated with IR in NDO humans. These findings indicate a pro-inflammatory role of 4-HNE in NDO patients, which supports the potential role of 4-HNE in the development of obesity-related disorders (AU)
Introducción: la prevalencia de la obesidad está aumentando en todo el mundo. El estrés oxidativo desempeña un papel etiológico en una variedad de desórdenes metabólicos relacionados con la obesidad. El hydroxynonenal 4 (4-HNE) es el aldehido más abundante y más reactivo derivado de la peroxidación de los ácidos grasos poliinsaturados n-6, con efectos biológicos diversos que no son bien conocidos. La obesidad se asocia a concentraciones disminuidas de adiponectinas en el plasma y a un aumento en los productos de la peroxidación lipídica, incluyendo el 4-HNE, en tejido adiposo. Puede haber una cierta asociación entre el nivel de adipoquinas y el 4-HNE. Material y métodos: para analizar las asociaciones entre 4-HNE y las adipoquinas clásicas, adiponectina y leptina se determinaron por ELISA los niveles de adiponectina y de leptina, así como de 4-HNE, en una población de 160 pacientes chinos obesos no diabéticos (NDO) y de 160 controles sanos, y se estudió su asociación con adiposidad, perfil glucémico y lipídico, secreción de la insulina y sensibilidad de la insulina. Resultados: los niveles de 4-HNE aumentaron significativamente en los pacientes con NDO comparado con los controles sanos (p < 0,01). El nivel de 4-HNE se correlacionó negativamente con la adiponectina y positivamente con la leptina. Los niveles de 4-HNE se correlacionan positivamente con el IMC y negativamente con la sensibilidad a la insulina. Conclusión: concluimos que el 4-HNE está asociado a la secreción de adiponectina y de leptina y correlacionado con la resistencia a la insulina en sujetos obesos no diabéticos. Estos resultados indican un papel proinfl amatorio del 4-HNE en pacientes NDO, que apoya el papel potencial del 4-HNE en el desarrollo de alteraciones relacionadas con la obesidad (AU)
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Obesidad/epidemiología , Inflamación/complicaciones , Inflamación/dietoterapia , Receptores de Adipoquina/uso terapéutico , Resistencia a la Insulina/fisiología , Estrés Oxidativo/fisiología , Leptina/metabolismo , Peroxidación de Lípido/fisiología , Ensayo de Inmunoadsorción Enzimática , Antropometría/métodosRESUMEN
BACKGROUND: The aim of the present study was to evaluate different signaling pathways by which exercise training would interfere in endothelial function in obesity. Therefore, we examined adipocytokine levels and their receptors in the corpus cavernosum and femoral artery from trained rats on a high-fat diet. METHODS: Functional experiments were performed in control sedentary and trained rats, and sedentary (h-SD) and trained male Wistar rats on a high-fat diet (h-TR). Nitric oxide (NO) and reactive oxygen species (ROS) were evaluated in vascular tissue. Circulating adipocytokines and their receptors were analyzed. RESULTS: In the h-SD group, the maximal responses to acetylcholine (ACh) were reduced in the femoral artery and corpus cavernosum as well as the electrical field stimulation, accompanied by an increase in circulating insulin, leptin, TNF-α, MCP-1, and PAI-1. Downregulation of ObR protein expression in the femoral artery was observed without alterations in AdipoR1 and TNFR1 in both preparations. A positive effect was observed in the h-TR group regarding the relaxation response to ACh and circulating adipocytokines, resulting in increased NO production and reduced ROS generation. Exercise restored the ObR protein expression only in the femoral artery. CONCLUSION: Aerobic exercise training ameliorated the inflammatory adipocytokines and restored the relaxation responses in the corpus cavernosum and femoral artery in rats on a high-fat diet.
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Adipoquinas/sangre , Dieta Alta en Grasa , Arteria Femoral/metabolismo , Pene/irrigación sanguínea , Condicionamiento Físico Animal , Receptores de Adipoquina/metabolismo , Vasoconstricción , Vasodilatación , Animales , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Arteria Femoral/efectos de los fármacos , Mediadores de Inflamación/sangre , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Receptores de Adiponectina/metabolismo , Receptores de Leptina/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Conducta Sedentaria , Transducción de Señal , Superóxido Dismutasa/metabolismo , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacologíaRESUMEN
AIM: Critically discuss the available data, to identify the current gaps and to provide key concepts that will help clinicians in translating the biology of adipokines in the context of atherosclerosis and cardio-metabolic diseases. DATA SYNTHESIS: Adipose tissue is nowadays recognized as an active endocrine organ, a function related to the ability to secrete adipokines (such as leptin and adiponectin) and pro-inflammatory cytokines (tumor necrosis factor alpha and resistin). Studies in vitro and in animal models have observed that obesity status presents a chronic low-grade inflammation as the consequence of the immune cells infiltrating the adipose tissue as well as adipocytes. This inflammatory signature is often related to the presence of cardiovascular diseases, including atherosclerosis and thrombosis. These links are less clear in humans, where the role of adipokines as prognostic marker and/or player in cardiovascular diseases is not as clear as that observed in experimental models. Moreover, plasma adipokine levels might reflect a condition of adipokine-resistance in which adipokine redundancy occurs. The investigation of the cardio-metabolic phenotype of carriers of single nucleotide polymorphisms affecting the levels or function of a specific adipokine might help determine their relevance in humans. Thus, the aim of the present review is to critically discuss the available data, identify the current gaps and provide key concepts that will help clinicians translate the biology of adipokines in the context of atherosclerosis and cardio-metabolic diseases.
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Adipoquinas/sangre , Tejido Adiposo/metabolismo , Aterosclerosis/sangre , Enfermedades Cardiovasculares/sangre , Investigación Biomédica Traslacional , Adipoquinas/genética , Tejido Adiposo/fisiopatología , Animales , Aterosclerosis/diagnóstico , Aterosclerosis/fisiopatología , Biomarcadores/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/fisiopatología , Citocinas/sangre , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Mediadores de Inflamación/sangre , Fenotipo , Pronóstico , Receptores de Adipoquina/metabolismo , Factores de Riesgo , Transducción de SeñalRESUMEN
Adipose tissue secretes a variety of bioactive substances that are associated with chronic inflammation, insulin resistance, and an increased risk of type 2 diabetes mellitus. While resistin was first known as an adipocyte-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents, it is predominantly expressed and secreted by macrophages in humans. Epidemiological and genetic studies indicate that increased resistin levels are associated with the development of insulin resistance, diabetes, and cardiovascular disease. Resistin also appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and the formation of foam cells. Thus, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with cardiovascular disease and heart failure. Furthermore, recent evidence suggests that resistin is associated with atherogenic dyslipidemia and hypertension. The present review will focus on the role of human resistin in the pathogeneses of inflammation and obesity-related diseases.
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Enfermedades Cardiovasculares/etiología , Inflamación/etiología , Enfermedades Metabólicas/etiología , Resistina/fisiología , Animales , Aterosclerosis/etiología , Humanos , Hipertensión/etiología , Resistencia a la Insulina/fisiología , Ratones , Obesidad/etiología , Receptores de Adipoquina/fisiología , Resistina/genéticaRESUMEN
Background: The aim of this paper is to investigated the contribution of adipose tissue thought the adipokines and kidney failure (KF) Methods: In male rats were fed with a standard lab diet (C) or a hypercaloric diet including 30% sucrose; obese group (Ob) and obese with kidney failure group (Ob/KF). We evaluated the changes of adipokines under conditions of obesity and KF, using 5/6 surgery to induce vascular injury. The anterior and media branches of the left kidney artery were tied together, leaving the posterior branch viable to enable the kidney to function. The right kidney was removed. Results: A 90% survival rate of the animals was achieved due to special care taken. Kidney function progressively decreased after surgery. Compared with the control group, in the other two groups (Ob and Ob/KF) the level of leptin increased and that of adiponectin decreased (p < 0.01). Post-surgery increases were observed in blood pressure, lipids, creatinine and insulin (p < 0.01). Conclusion: This model is proposed for the study pathophysiological mechanisms that lead to obesity and complications of kidney or cardiovascular function.
Introducción: El objetivo de este trabajo es investigar la contribución del tejido adiposo y las adipocinas y la insuficiencia renal (KF). Métodos: Ratas machos se alimentaron con una dieta estándar de laboratorio (C) o una dieta hipercalórica incluyendo 30% de sacarosa; Grupo obeso (Ob) y obeso con grupo de insuficiencia renal (Ob/KF). Se evaluaron los cambios de adipocinas en condiciones de obesidad y KF, utilizando cirugía 5/6 para inducir lesión vascular. Las ramas anterior y media de la arteria renal izquierda fueron unidas, dejando la rama posterior viable para permitir sobreviviencia y función renal. El riñón derecho fue removido. Resultados: Se logró una tasa de supervivencia del 90% de los animales debido a un cuidado especial. La función renal disminuyó progresivamente después de la cirugía. En comparación con el grupo control, en los otros dos grupos (Ob y Ob/KF) el nivel de leptina aumentó y el de adiponectina disminuyó (p < 0.01). Se observaron aumentos postquirúrgicos en la presión arterial, los lípidos, la creatinina y la insulina (p < 0.01). Conclusión: Este modelo se propone para el estudio de los mecanismos fisiopatológicos que conducen a la obesidad y las complicaciones de la función renal o cardiovascular.
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Adipoquinas/metabolismo , Hipertensión/metabolismo , Obesidad/metabolismo , Receptores de Adipoquina/metabolismo , Insuficiencia Renal/metabolismo , Animales , Biomarcadores/metabolismo , Hipertensión/complicaciones , Masculino , Obesidad/complicaciones , Ratas , Insuficiencia Renal/complicacionesRESUMEN
BACKGROUND: Clinacanthus nutans is used traditionally in many parts of Asia to improve well-being, but there are limited studies on its efficacy. We explored the potential use of C. nutans for prevention of high fat and high cholesterol diet-(HFHC-) induced insulin resistance in rats. METHODS: The leaf of C. nutans was extracted using water (AL extract) and methanol (AML extract), and the extracts were fed to rats alongside the HFHC diet for 7 weeks, and compared with simvastatin. Oral glucose tolerance test, and serum insulin, retinol binding protein 4 (RBP4), adiponectin and leptin were measured. Homeostatic model assessment of insulin resistance (HOMA-IR) was computed, while transcriptional regulation of hepatic insulin signaling genes was also assessed. RESULTS: Glycemic response was higher in the HFHC group compared with the AL and AML groups, which also had lower serum RBP4, fasting glucose, insulin and HOMA-IR. Serum adiponectin levels were higher, while leptin levels were lower in the AML and AL groups compared to the HFHC group. There was upregulation of the Insulin receptor substrate, phosphotidyl inositol-3-phosphate, adiponectin receptor and leptin recetor genes, in comparison with the HFHC group. CONCLUSIONS: Overall, the results showed that the HFHC diet worsened metabolic indices and induced insulin resistance partly through transcriptional regulation of the insulin signaling genes. C.nutans, on the other hand, attenuated the metabolic effects and transcriptional changes induced by the HFHC diet. The results suggested that C.nutans may be a good source of functional ingredient for the prevention of insulin resistance.
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Acanthaceae/química , Glucemia/metabolismo , Dieta Alta en Grasa , Grasas de la Dieta/efectos adversos , Resistencia a la Insulina , Insulina/sangre , Fenoles/farmacología , Adiponectina/sangre , Animales , Colesterol en la Dieta/efectos adversos , Proteínas Sustrato del Receptor de Insulina/genética , Proteínas Sustrato del Receptor de Insulina/metabolismo , Resistencia a la Insulina/genética , Leptina/sangre , Fosfatos de Fosfatidilinositol/genética , Fosfatos de Fosfatidilinositol/metabolismo , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas Sprague-Dawley , Receptores de Adipoquina/genética , Receptores de Adipoquina/metabolismo , Proteínas Plasmáticas de Unión al Retinol/metabolismo , Transcripción Genética/efectos de los fármacosRESUMEN
The transition from pregnancy to lactation is characterized by major changes in glucose and adipose tissue metabolism. Anti- and prolipolytic pathways mediated via the hydroxycarboxylic acid receptors 1 (HCAR1) and 2 (HCAR2) and tumor necrosis factor-α receptor 1 (TNFR1), as well as the adipokines apelin and resistin, are likely involved in regulating these processes. This study aimed to determine the mRNA abundance of the aforementioned receptors in both subcutaneous and visceral adipose tissue, to characterize the adipokine concentrations in serum, and to test the effects of feeding diets with either high or low portions of concentrate and a concomitant niacin supplementation from late gestation to early lactation. Twenty pluriparous German Holstein cows were all kept on the same silage-based diet until d 42 antepartum, when they were allocated to 2 feeding groups: until d 1 antepartum, 10 animals each were assigned to either a high-concentrate (60:40 concentrate-to-roughage ratio) or a low-concentrate diet (30:70). Both groups were further subdivided into a control and a niacin group, the latter receiving 24 g/d of nicotinic acid from d -42 until 24. From d 1 to 24 postpartum, the concentrate portion was increased from 30 to 50% for all cows. Biopsies of subcutaneous (SCAT) and retroperitoneal adipose tissue (RPAT) were taken at d -42, 1, 21, and 100 relative to parturition. Blood samples were drawn along with the biopsies and on d -14, 3, 7, 14, and 42. The concentrations of the adipokines apelin and resistin in serum were measured via ELISA. The mRNA of the 3 receptors in AT was quantified as well as the protein abundance of HCAR2 by Western blot. The feeding regimen did not affect the variables examined. The concentrations of apelin remained fairly constant during the observation period, whereas the resistin concentrations increased toward parturition and decreased to precalving levels within 1 wk after calving. The mRNA abundance of HCAR1, HCAR2, and TNFR1 changed in SCAT and RPAT during the considered time period. For the HCAR2 protein, time-dependent changes were restricted to SCAT. The mRNA abundance of all receptors was greater in RPAT than in SCAT. The tissue-specific correlations observed between the receptors point to a link between these factors and may indicate different regulatory roles in the respective tissues. This study provides insight into the complex metabolic adaptations during the transition period and supports a differential regulation of lipolysis among SCAT and RPAT in dairy cows.
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Adipoquinas/metabolismo , Tejido Adiposo/metabolismo , Bovinos/fisiología , Grasa Intraabdominal/metabolismo , Resistina/metabolismo , Adipoquinas/genética , Animales , Dieta/veterinaria , Fibras de la Dieta/análisis , Suplementos Dietéticos/análisis , Femenino , Lactancia , Lipólisis , Parto , Periodo Posparto , Embarazo , Receptores de Adipoquina/genética , Receptores de Adipoquina/metabolismo , Resistina/genética , Ensilaje/análisisRESUMEN
El tejido adiposo blanco juega un papel importante en el mantenimiento de la homeostasis energética corporal mediante el almacenamiento de triglicéridos y la secreción de adipoquinas que son importantes para la regulación del metabolismo lipídico y de la glucosa. La disfunción adipocítica en la obesidad incluye la secreción de niveles anormales de citoquinas asociadas a la resistencia a la insulina, falla en el almacenamiento de los triglicéridos y una lipólisis incrementada. Estas anormalidades pueden contribuir a un nivel aumentado de ácidos grasos circulantes y llevar a una sobrecarga de ácidos grasos en el músculo esquéletico y en el hígado. Tales aumentos de ácidos grasos en estos compartimentos se asocian a una respuesta disminuida a la insulina en estos tejidos en la obesidad.
Human white adipose tissue plays a pivotal role in maintaining whole-body energy homeostasis by storing triglycerides and secreting adipokines that are important for regulating lipid and glucose metabolism. Adipose dysfunction in obesity include secretions of abnormal levels of cytokines linked to insulin resistance, impairments in triglyceride storage and increases in lipolysis. These abnormalities in turn can contribute to increased fatty acids in the circulation and lead to an overload of fatty acids in the skeletal muscle and the liver. Such increases in fatty acids in these compartments are likely to cause decreased responsiveness to insulin in these tissue in obesity.