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1.
Gen Comp Endocrinol ; 267: 146-156, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29953882

RESUMO

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 15 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.


Assuntos
Adipocinas/genética , Tecido Adiposo/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Fígado/metabolismo , Músculos Peitorais/metabolismo , Adipocinas/química , Adipocinas/metabolismo , Sequência de Aminoácidos , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Embrião de Galinha , Galinhas/metabolismo , Tamanho do Órgão , Óvulo/metabolismo , Receptores de Adipocina/genética , Receptores de Adipocina/metabolismo
2.
PLoS One ; 12(10): e0187068, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29073286

RESUMO

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.


Assuntos
Leucócitos/citologia , Obesidade/metabolismo , Receptores de Adipocina/metabolismo , Adipocinas/sangue , Adolescente , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Citometria de Fluxo , Humanos , Masculino , Obesidade/sangue
3.
Int J Mol Sci ; 18(4)2017 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-28422056

RESUMO

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.


Assuntos
Adiponectina/metabolismo , Transformação Celular Neoplásica/metabolismo , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/metabolismo , Citocinas/metabolismo , Lectinas/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Adipocinas/metabolismo , Animais , Proteínas de Transporte/metabolismo , Neoplasias Colorretais/epidemiologia , Proteínas Ligadas por GPI/metabolismo , Humanos , Leptina/metabolismo , Proteínas de Membrana/metabolismo , Obesidade/epidemiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Sobrepeso/metabolismo , Receptores de Adipocina/metabolismo
4.
J Vasc Res ; 54(1): 33-50, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28288470

RESUMO

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.


Assuntos
Adipocinas/sangue , Dieta Hiperlipídica , Artéria Femoral/metabolismo , Pênis/irrigação sanguínea , Condicionamento Físico Animal , Receptores de Adipocina/metabolismo , Vasoconstrição , Vasodilatação , Animais , Relação Dose-Resposta a Droga , Estimulação Elétrica , Artéria Femoral/efeitos dos fármacos , Mediadores da Inflamação/sangue , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Receptores de Adiponectina/metabolismo , Receptores para Leptina/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Comportamento Sedentário , Transdução de Sinais , Superóxido Dismutase/metabolismo , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia
5.
Nutr Metab Cardiovasc Dis ; 27(5): 379-395, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28237179

RESUMO

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.


Assuntos
Adipocinas/sangue , Tecido Adiposo/metabolismo , Aterosclerose/sangue , Doenças Cardiovasculares/sangue , Pesquisa Médica Translacional , Adipocinas/genética , Tecido Adiposo/fisiopatologia , Animais , Aterosclerose/diagnóstico , Aterosclerose/fisiopatologia , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Citocinas/sangue , Predisposição Genética para Doença , Variação Genética , Humanos , Mediadores da Inflamação/sangue , Fenótipo , Prognóstico , Receptores de Adipocina/metabolismo , Fatores de Risco , Transdução de Sinais
6.
Korean J Intern Med ; 32(2): 239-247, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28192887

RESUMO

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.


Assuntos
Doenças Cardiovasculares/etiologia , Inflamação/etiologia , Doenças Metabólicas/etiologia , Resistina/fisiologia , Animais , Aterosclerose/etiologia , Humanos , Hipertensão/etiologia , Resistência à Insulina/fisiologia , Camundongos , Obesidade/etiologia , Receptores de Adipocina/fisiologia , Resistina/genética
7.
Rev Med Inst Mex Seguro Soc ; 55(Suppl 4): S358-S364, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29792610

RESUMO

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.


Assuntos
Adipocinas/metabolismo , Hipertensão/metabolismo , Obesidade/metabolismo , Receptores de Adipocina/metabolismo , Insuficiência Renal/metabolismo , Animais , Biomarcadores/metabolismo , Hipertensão/complicações , Masculino , Obesidade/complicações , Ratos , Insuficiência Renal/complicações
8.
BMC Complement Altern Med ; 16: 88, 2016 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-26924713

RESUMO

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.


Assuntos
Acanthaceae/química , Glicemia/metabolismo , Dieta Hiperlipídica , Gorduras na Dieta/efeitos adversos , Resistência à Insulina , Insulina/sangue , Fenóis/farmacologia , Adiponectina/sangue , Animais , Colesterol na Dieta/efeitos adversos , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina/genética , Leptina/sangue , Fosfatos de Fosfatidilinositol/genética , Fosfatos de Fosfatidilinositol/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos Sprague-Dawley , Receptores de Adipocina/genética , Receptores de Adipocina/metabolismo , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Transcrição Genética/efeitos dos fármacos
9.
J Dairy Sci ; 99(2): 1549-1559, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26686707

RESUMO

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.


Assuntos
Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Bovinos/fisiologia , Gordura Intra-Abdominal/metabolismo , Resistina/metabolismo , Adipocinas/genética , Animais , Dieta/veterinária , Fibras na Dieta/análise , Suplementos Nutricionais/análise , Feminino , Lactação , Lipólise , Parto , Período Pós-Parto , Gravidez , Receptores de Adipocina/genética , Receptores de Adipocina/metabolismo , Resistina/genética , Silagem/análise
10.
Future Med Chem ; 7(2): 139-57, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25686003

RESUMO

Adipose tissue is an 'endocrine organ' that influences diverse physiological and pathological processes via adipokines secretion. Strong evidences suggest that epicardial and perivascular adipose tissue can directly regulate heart and vessels' structure and function. Indeed, in obesity there is a shift toward the secretion of adipokines that promote a pro-inflammatory status and contribute to obesity cardiomyopathy. The prospect of modulating adipokines and/or their receptors represents an attractive perspective to the treatment of cardiovascular diseases. In this paper, we described the most important actions of certain adipokines and their receptors that are capable of influencing cardiovascular physiology as well as their possible use as therapeutic targets.


Assuntos
Adipocinas/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Receptores de Adipocina/antagonistas & inibidores , Adipocinas/química , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Humanos , Modelos Biológicos , Receptores de Adipocina/metabolismo
11.
J Physiol Biochem ; 71(3): 537-46, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25686566

RESUMO

Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness.


Assuntos
Adipócitos/metabolismo , Endométrio/metabolismo , Infertilidade Feminina/metabolismo , Obesidade/metabolismo , Células 3T3-L1 , Adulto , Animais , Meios de Cultivo Condicionados , Endométrio/patologia , Células Epiteliais/metabolismo , Feminino , Fertilidade , Expressão Gênica , Humanos , Infertilidade Feminina/etiologia , Camundongos , Obesidade/complicações , Comunicação Parácrina , Receptores de Adipocina/metabolismo , Adulto Jovem
12.
PLoS One ; 8(6): e66284, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23750285

RESUMO

Breast cancer has become the most common cancer among women in industrialized countries. Obesity is well established as a risk factor, in particular owing to the attendant secretion of the entities called adipokines; there is growing evidence for a role of cells and factors present in the mammary tumor microenvironment such as fibroblasts, preadipocytes, adipocytes and their secretions. To study how the microenvironment influences breast cancer growth, we developed a novel tridimensional adipose model epithelialized with normal human keratinocytes or with breast cancer cell lines. These mimicked a breast tumor in contact with an adipose microenvironment and allowed monitoring of the interactions between the cells. Leptin and adiponectin, two major adipokines, and their respective receptors, ObRt and AdipoR1, were expressed in the model, but not the second adiponectin receptor, AdipoR2. The differentiation of preadipocytes into adipocytes was greater when they were in contact with the breast cancer cell lines. The contact of breast cancer cell lines with the microenvironment completely modified their transcriptional programs by increasing the expression of genes involved in cell proliferation (cyclinD1, MAPK), angiogenesis (MMP9, VEGF) and hormonal pathways (ESR1, IL6). This tridimensional adipose model provides new insights into the interactions between breast cancer cells and their adipose microenvironment, and provides a tool to develop new drugs for the treatment of both cancer and obesity.


Assuntos
Tecido Adiposo/patologia , Neoplasias da Mama/patologia , Modelos Biológicos , Microambiente Tumoral , Adipocinas/metabolismo , Neoplasias da Mama/genética , Diferenciação Celular , Linhagem Celular Tumoral , Criança , Células Epiteliais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Queratinócitos/patologia , Receptores de Adipocina/metabolismo , Transcrição Genética
13.
Hypertension ; 61(2): 431-6, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23266543

RESUMO

Renin-angiotensin system, metabolic abnormalities, and immune activity have a role in the pathogenesis of primary hypertension. We assessed the leukocyte mRNA expression of angiotensinogen, angiotensin converting enzyme, renin, angiotensin 2 type 1 receptor, CD14 molecule, adiponectin type 1 receptor, and leptin receptor in hypertensive children before and after nonpharmacological treatment. Leukocyte mRNA expression was measured by means of quantitative real-time reverse transcriptase-polymerase chain reaction in 23 hypertensive children before and after 6 months of nonpharmacological treatment based on dietary advice and physical activities. Twenty-three normotensive children matched for age, sex, and body mass index served as a control group. Before treatment patients had elevated expression of angiotensin converting enzyme and CD14 mRNA, decreased expression of angiotensinogen and angiotensin type 1 receptor mRNA, and unchanged expression of renin, adiponectin, and leptin receptors mRNA as compared with controls. Renin mRNA negatively correlated with 24-hour mean arterial pressure and carotid intima-media thickness. Six months of nonpharmacological treatment caused decrease of blood pressure and normalization of metabolic abnormalities. Renin, adiponectin, and leptin receptors mRNA expression decreased and were lower than in control group. Changes in blood pressure, left ventricular mass, carotid intima-media thickness, body mass index, and waist circumference did not correlate with changes in the expression of renin-angiotensin system genes, CD14, leptin, and adiponectin receptors mRNA. We conclude that leukocytes of hypertensive children displayed alterations in the expression of renin-angiotensin system genes as well as those of CD14. Nonpharmacological treatment resulted in downregulation of genes involved in renin-angiotensin activation and those engaged in leukocyte responses to adipokines.


Assuntos
Pressão Sanguínea/genética , Hipertensão/genética , Sistema Imunitário/fisiopatologia , Leucócitos/metabolismo , Receptores de Adipocina/genética , Sistema Renina-Angiotensina/genética , Adolescente , Índice de Massa Corporal , Espessura Intima-Media Carotídea , Criança , Dieta , Regulação para Baixo/genética , Feminino , Humanos , Hipertensão/imunologia , Hipertensão/terapia , Sistema Imunitário/metabolismo , Masculino , Atividade Motora , Receptores de Adipocina/metabolismo , Circunferência da Cintura
14.
J Cell Physiol ; 226(11): 2790-7, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21935928

RESUMO

Although extensive evidence support the key role of adipokines in cartilage homeostasis, contradictory data have been found for their expression and their effects in chondrocytes. This study was then undertaken to determine whether a phenotypic modulation may affect the expression of adipokines and their receptors in human chondrocytes. The expression of leptin, adiponectin and their receptors, as well as cartilage-specific genes was examined in chondrocytes obtained from patients with osteoarthritis either directly after cells harvest or after culture in monolayer or in alginate beads. The results showed major changes in the gene expression pattern after culture in monolayer with a shift from the adipokines to their receptors. Interestingly, this downregulation of adipokines was associated with a loss of chondrocyte phenotype, and chondrocytes recovered a cartilage-like expression profile of leptin and adiponectin when cultured in a tridimensional chondrocyte phenotype-inducing system, but ceased expressing their receptors. Further experiments clearly showed that leptin but not adiponectin promoted the expression of cartilage-specific markers through mitogen-activated protein kinase, Janus kinase and phosphatidylinositol-3 kinase signaling pathways. In conclusion, our data indicate that any phenotypic modulation could affect chondrocyte responsiveness to leptin or adiponectin, and provide evidence for an important role for leptin in regulating the expression of cartilage-specific markers.


Assuntos
Adipocinas/metabolismo , Cartilagem/metabolismo , Condrócitos/metabolismo , Leptina/metabolismo , Receptores de Adipocina/metabolismo , Adipocinas/genética , Adiponectina/genética , Adiponectina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Células Cultivadas , Perfilação da Expressão Gênica , Humanos , Janus Quinases/metabolismo , Leptina/genética , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Osteoartrite/metabolismo , Fenótipo , Fosfatidilinositol 3-Quinases/metabolismo , Receptores de Adipocina/genética , Transdução de Sinais
15.
Cell Signal ; 23(9): 1455-65, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21536126

RESUMO

Neuropeptides of the adipokinetic hormone (AKH) family play important roles in insect hemolymph sugar homeostasis, larval lipolysis and storage-fat mobilization. Our previous studies have shown that the adipokinetic hormone receptor (AKHR), a Gs-coupled receptor, induces intracellular cAMP accumulation, calcium mobilization and ERK1/2 phosphorylation upon agonist stimulation. However, the underlying molecular mechanisms that regulate the internalization and desensitization of AKHR remain largely unknown. In the current study we made a construct to express AKHR fused with enhanced green fluorescent protein (EGFP) at its C-terminal end to further characterize AKHR internalization. In stable AKHR-EGFP-expressing HEK-293 cells, AKHR-EGFP was mainly localized at the plasma membrane and was rapidly internalized in a dose- and time-dependent manner via the clathrin-coated pit pathway upon agonist stimulation, and internalized receptors were slowly recovered to the cell surface after the removal of AKH peptides. The results derived from RNA interference and arrestin translocation demonstrated that G protein-coupled receptor kinase 2 and 5 (GRK2/5) and ß-arrestin2 were involved in receptor phosphorylation and internalization. Furthermore, experiments using deletion and site-directed mutagenesis strategies identified the three residues (Thr356, Ser359 and Thr362) responsible for GRK-mediated phosphorylation and internalization and the C-terminal domain from residue-322 to residue-342 responsible for receptor export from ER. This is the first detailed investigation of the internalization and trafficking of insect G protein-coupled receptors.


Assuntos
Bombyx/metabolismo , Membrana Celular/metabolismo , Quinases de Receptores Acoplados a Proteína G/metabolismo , Proteínas de Insetos/metabolismo , Receptores de Adipocina/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Sequência de Aminoácidos , Animais , Arrestinas/metabolismo , Cálcio/metabolismo , Vesículas Revestidas por Clatrina/metabolismo , Clonagem Molecular , Invaginações Revestidas da Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Citometria de Fluxo , Técnicas de Silenciamento de Genes , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Células HeLa , Humanos , Proteínas de Insetos/química , Microscopia de Fluorescência , Dados de Sequência Molecular , Mutagênese Insercional , Fosforilação , Transporte Proteico , Interferência de RNA , Receptores de Adipocina/química , Proteínas Recombinantes de Fusão/metabolismo , Deleção de Sequência , Transdução de Sinais , Transfecção , beta-Arrestinas
16.
J Clin Endocrinol Metab ; 96(4): E606-13, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21289263

RESUMO

CONTEXT: Low-grade inflammation links obesity, type 2 diabetes mellitus (T2DM), and cardiovascular diseases. OBJECTIVE: To explore the expression profile of genes involved in inflammatory pathways in adipose tissue and peripheral monocytes (PM) of obese patients with and without T2DM at baseline and after dietary intervention. DESIGN: Two-week intervention study with very-low-calorie diet (VLCD). SETTING: University hospital. PATIENTS: Twelve obese females with T2DM, 8 obese nondiabetic females (OB) and 15 healthy age-matched females. INTERVENTION: Two weeks of VLCD (2500 kJ/d). MAIN OUTCOME MEASURES: Metabolic parameters, circulating cytokines, hormones, and mRNA expression of 39 genes in sc adipose tissue (SCAT) and PM. RESULTS: Both T2DM and OB group had significantly increased serum concentrations of circulating proinflammatory factors (C-reactive protein, TNFα, IL-6, IL-8), mRNA expression of macrophage antigen CD68 and proinflammatory chemokines (CCL-2, -3, -7, -8, -17, -22) in SCAT and complementary chemokine receptors (CCR-1, -2, -3, -5) and other proinflammatory receptors (toll-like receptor 2 and 4, TNF receptor superfamily 1A and 1B, IL-6R) in PM, with OB group showing less pronounced chemoattracting and proinflammatory profile compared to T2DM group. In T2DM patients VLCD decreased body weight, improved metabolic profile, and decreased mRNA expression of up-regulated CCRs in PM and chemokines [CCL 8, chemokine (C-X-C motif) ligand 10] in SCAT. VLCD markedly increased mRNA expression of T-lymphocyte attracting chemokine CCL-17 in SCAT. CONCLUSION: Obese patients with and without T2DM have increased mRNA expression of chemotactic and proinflammatory factors in SCAT and expression of corresponding receptors in PM. Two weeks of VLCD significantly improved this profile in T2DM patients.


Assuntos
Restrição Calórica , Diabetes Mellitus Tipo 2/dietoterapia , Regulação da Expressão Gênica , Inflamação/genética , Monócitos/metabolismo , Obesidade/dietoterapia , RNA Mensageiro/genética , Gordura Subcutânea/metabolismo , Adipocinas/genética , Adipocinas/metabolismo , Quimiocinas/genética , Quimiocinas/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Dieta Redutora , Feminino , Humanos , Inflamação/complicações , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/genética , RNA Mensageiro/metabolismo , Receptores de Adipocina/genética , Receptores de Adipocina/metabolismo , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo
17.
Wien Med Wochenschr ; 160(15-16): 377-90, 2010 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-20812049

RESUMO

The prevalence of obesity is rising worldwide. Recent research findings show that adipose tissue is a highly active endocrine organ, which is involved in many physiological processes. These metabolic processes are influenced by products of the adipose tissue, so-called adipokines, which play a crucial role in the pathogenesis of the metabolic syndrome and cardiovascular disease. In addition, the two major fat depots - intraabdominal and subcutaneous - differ in their ability to secrete adipokines. In recent years the importance of the association between intraabdominal fat and the development of insulin resistance, diabetes mellitus type 2 and dyslipidemia was recognized. Therefore, accumulation of visceral adipose tissue contributes due to its ability to secrete a different pattern of adipokines to increased morbidity and mortality. This review aims to characterize novel, newly recognized adipokines and to discuss their roles in the pathogenesis of insulin resistance and atherosclerosis, as well as other metabolic complications.


Assuntos
Adipocinas/fisiologia , Aterosclerose/fisiopatologia , Resistência à Insulina/fisiologia , Obesidade Abdominal/fisiopatologia , Adipócitos/fisiologia , Adiponectina/fisiologia , Animais , Apelina , Encéfalo/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Quimiocinas/fisiologia , Fator D do Complemento/fisiologia , Citocinas/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Proteínas de Ligação a Ácido Graxo/fisiologia , Feminino , Proteínas Ligadas por GPI/fisiologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Lectinas/fisiologia , Masculino , Síndrome Metabólica/fisiopatologia , Receptores de Adipocina/fisiologia , Resistina/fisiologia , Proteínas Plasmáticas de Ligação ao Retinol/fisiologia , Serpinas/fisiologia
19.
Domest Anim Endocrinol ; 39(2): 97-105, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20399065

RESUMO

Recently, we reported that chemerin, a new adipokine, is highly expressed in the adipose tissue, up-regulated during adipocyte differentiation, and regulates adipogenesis via its own receptor in mice. The objectives of this study were to clone chemerin and its receptor from the adipose tissues of Japanese Black cattle and to investigate the expression of these genes in 16 different tissues. We compared the gene expression of chemerin and its receptor between adipocytes and stromal-vascular (S-V) cells (non-adipocytes) prepared from subcutaneous adipose tissue. In addition, we investigated the mRNA expression levels of chemerin and its receptor in bovine differentiated adipocytes. The DNA sequences of bovine chemerin and its receptor were determined, and they were found to be highly homologous to those of humans, mice, and pigs. The amino acid sequences predicted for the full-length cDNA of bovine chemerin and its receptor were also similar to those of humans, mice, and pigs, suggesting that these genes have similar functions. Bovine chemerin mRNA was highly expressed in the adipose and liver tissues, and the transcripts of chemerin receptor were widely expressed in several tissues including adipose, muscle, liver, and brain tissues. The expression of bovine chemerin mRNA was higher in adipocytes than in S-V cells prepared from adipose tissue. The transcripts of chemerin and its receptor were up-regulated during adipocyte differentiation. Treatment with tumor necrosis factor (TNF)-alpha (10 ng/mL) in bovine differentiated adipocytes increased the mRNA expression of chemerin and its receptor. These results indicate that chemerin, a new adipokine highly expressed in the adipocytes of bovine adipose tissue, is the TNF-alpha-up-regulated gene with a role in adipogenesis.


Assuntos
Adipogenia/genética , Adipocinas/genética , Bovinos/genética , Perfilação da Expressão Gênica , Receptores de Adipocina/genética , Adipócitos/citologia , Adipócitos/metabolismo , Adipogenia/fisiologia , Adipocinas/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Bovinos/metabolismo , Diferenciação Celular , Clonagem Molecular , Simulação por Computador , Feminino , Regulação da Expressão Gênica , Dados de Sequência Molecular , RNA Mensageiro/análise , Receptores de Adipocina/metabolismo , Homologia de Sequência , Estatísticas não Paramétricas , Distribuição Tecidual
20.
Genetika ; 44(10): 1338-55, 2008 Oct.
Artigo em Russo | MEDLINE | ID: mdl-19062531

RESUMO

Subcutaneous and visceral adipose compartments act, not only as fatty acid depots, but also as active endocrine organs that undergo hyperplastic changes and significantly enhance their function in obesity. Akipokines and other proteins secreted by both adipocytes and stromal cells play a central role in peripheral insulin resistance and the metabolic syndrome (MS). Minor alleles of the adipokine genes substantially contribute to MS. The most important consequence of MS is low-level systemic inflammation supported by adipose-specific synthesis of proinflammatory soluble molecules. Proinflammatory signals are secreted into the bloodstream and spread to peripheral tissues that contain their receptors. The signals provided by adipose tissue stimulate the development of secondary complications of MS, including cardiovascular disorders (CVDs) and nonalcoholic fatty liver disease. The review describes the physiological effects of adiponectin, leptin, resistin, visfatin, and apelin and the influence of the minor alleles of the adipokine genes on the development of the secondary complications of MS.


Assuntos
Adipocinas/genética , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Glândulas Endócrinas/metabolismo , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Adipócitos/metabolismo , Alelos , Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Humanos , Resistência à Insulina/genética , Receptores de Adipocina/genética , Receptores de Adipocina/metabolismo , Células Estromais/metabolismo
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