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1.
Domest Anim Endocrinol ; 65: 95-100, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30086525

RESUMO

Work in cattle and rodents has shown that resistin, in addition to its roles in insulin resistance and inflammation, is involved in the regulation of gonadal steroidogenesis. However, the role of resistin in the regulation of reproductive processes in other species, such as seasonally breeding sheep, is completely unknown. Herein, we tested the hypothesis that resistin can influence the secretion of anterior pituitary hormones and that its effect in ewes is dependent on the day length. Thirty Polish Longwool ewes, a breed that exhibits a strong seasonal reproductive pattern, were ovariectomized with estrogen replacement using subcutaneously inserted estradiol implants. Ewes were fed ad libitum and housed under a natural photoperiod (longitude: 19°57' E, latitude: 50° 04' N). Intravenous treatments consisted of control or recombinant bovine resistin (rbresistin) in saline: (1) control (saline; n = 10), (2) low resistin dose (1.0 µg/kg BW; n = 10), and (3) high resistin dose (10.0 µg/kg BW; n = 10). Experiments were conducted during both short-day (SD) and long-day (LD) seasons using 5 sheep per group within each season. Blood samples were collected every 10 min over 4 h. Blood plasma concentrations of FSH, LH, and prolactin (PRL) were assayed using RIA. A season × dose interaction was observed for all hormonal variables measured. Greater concentrations (P < 0.001) of LH and FSH were observed during SDs than during LDs in all groups. During SDs, the high dose (10 µg/kg BW) decreased (P < 0.001) basal LH levels and amplitude (P < 0.05) of LH pulses and increased (P < 0.001) circulating concentrations of FSH. However, the low dose of resistin decreased (P < 0.001) FSH concentrations compared to those of controls. During LDs, both the low and high resistin doses increased mean concentrations of LH (P < 0.001 and P < 0.05, respectively) and FSH (P < 0.001). A high dose of rbresistin increased (P < 0.001) the mean circulating concentrations of PRL during both seasons. However, in all groups, concentrations of PRL were greater during LDs than SDs. These results demonstrate for the first time that resistin is involved in the regulation of pituitary hormone secretion and that this effect is differentially mediated during LDs and SDs.


Assuntos
Gonadotropinas Hipofisárias/metabolismo , Adeno-Hipófise/metabolismo , Resistina/fisiologia , Estações do Ano , Ovinos/fisiologia , Animais , Relação Dose-Resposta a Droga , Implantes de Medicamento , Estradiol/administração & dosagem , Feminino , Hormônio Foliculoestimulante/sangue , Gonadotropinas Hipofisárias/sangue , Hormônio Luteinizante/sangue , Ovariectomia , Fotoperíodo , Prolactina/sangue , Resistina/administração & dosagem , Resistina/farmacologia
2.
Med Sci Monit ; 24: 6010-6020, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30156215

RESUMO

BACKGROUND Endothelial dysfunction plays a central part in the pathogenesis of coronary atherosclerosis. The adipokine resistin is one of the key players in endothelial cell dysfunction. In addition, the role of epicardial fat in coronary artery endothelial dysfunction is also emphasized. We investigated whether vasodilator-stimulated phosphoprotein (VASP) is involved in resistin-related endothelial dysfunction and the phenotype conversion of epicardial adipocytes. MATERIAL AND METHODS Cell proliferation and migration were evaluated by MTT and Transwell chamber assay, respectively. Next, we took epicardial fat samples from patients with valvular heart disease and non- coronary artery disease. Gene expression was determined by reverse transcription- quantitative polymerase chain reaction and relative abundance of the protein by Western blotting. RESULTS Resistin induced endothelial proliferation and migration in a dose-dependent manner. Both resistin-induced cell proliferation and migration were effectively blocked by ablation of VASP. The brown adipose tissue-specific genes for uncoupling protein 1 (UCP-1) and PR-domain-missing16 (PRDM16) decreased, but the white adipose tissue-specific genes for resistin and RIP140 increased in VASP-deficient adipocytes compared with the LV-sicntr group. However, disruption of the Ras homolog gene family member A (RhoA) /Rho-associated kinase (ROCK) in VASP-deficient adipocytes with specific inhibitors inverted the adipocyte phenotype existing in VASP-deficient adipocytes. Furthermore, the expressions of proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractantprotein-1 (MCP-1) in VASP-deficient adipocytes were markedly upregulated compared with the LV-sicntr group. CONCLUSIONS These results suggest a physiological role for VASP in coronary atherosclerosis through regulating adipokine resistin and phenotype conversion of epicardial adipose tissue.


Assuntos
Adipócitos/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Proteínas dos Microfilamentos/metabolismo , Fosfoproteínas/metabolismo , Resistina/fisiologia , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Adulto , Moléculas de Adesão Celular/genética , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doença da Artéria Coronariana/metabolismo , Citocinas/metabolismo , Humanos , Interleucina-6/análise , Interleucina-6/metabolismo , Proteínas dos Microfilamentos/genética , Pessoa de Meia-Idade , Pericárdio/efeitos dos fármacos , Pericárdio/metabolismo , Fenótipo , Fosfoproteínas/genética , Resistina/metabolismo
3.
J Endocrinol ; 238(1): 77-89, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29773580

RESUMO

Autophagy is a non-selective degradation pathway induced in energy-deprived cells and in non-starved cells by participating in cellular inflammatory responses mainly through the elimination of injured and aged mitochondria that constitute an important source of reactive oxygen species. We have previously reported that resistin/TLR4 signaling pathway induces inflammation and insulin resistance in neuronal cell. However, the impact of resistin-induced inflammation on neuronal autophagy is unknown. In the present study, we hypothesized that resistin-induced neuroinflammation could be attributed, at least partially, to the impairment of autophagy pathways in neuronal cells. Our data show that resistin decreases neuronal autophagy as evidenced by the repression of the main autophagy markers in SH-SY5Y human neuroblastoma cell line. Furthermore, the silencing of TLR4 completely abolished these effects. Resistin also inhibits AMPK phosphorylation and increases that of Akt/mTOR contrasting with activated autophagy where AMPK phosphorylation is augmented and mTOR inhibited. In vivo, resistin treatment inhibits the mRNA expression of autophagy markers in the hypothalamus of WT mice but not in Tlr4-/- mice. In addition, resistin strongly diminished LC3 (a marker of autophagy) labeling in the arcuate nucleus of WT mice, and this effect is abolished in Tlr4-/- mice. Taken together, our findings clearly reveal resistin/TLR4 as a new regulatory pathway of neuronal autophagy.


Assuntos
Autofagia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Resistina/farmacologia , Receptor 4 Toll-Like/fisiologia , Animais , Autofagia/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/fisiologia , Resistina/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Receptor 4 Toll-Like/genética , Células Tumorais Cultivadas
4.
Curr Probl Cancer ; 42(2): 208-214, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29433827

RESUMO

A substantial number of studies have revealed that a growing list of cancers might be influenced by obesity. In this regard, one of the most prominent and well-characterized cancers is breast cancer, the leading cause of cancer death among women. Obesity is associated with an increased risk for the occurrence and development of breast cancer particular in postmenopausal women. Moreover, the relationship between adiposity and breast cancer risk is complex, with associations that differ depending on when body size is assessed (eg, premenopausal vs postmenopausal obesity) and when breast cancer is diagnosed (ie, premenopausal vs postmenopausal disease). Obesity is mainly due to excessive fat accumulation in the regional tissue. Adipocytes in obese individuals produce endocrine, inflammatory, and angiogenic factors to affect adjacent breast cancer cells. Adipocytokines, are biologically active polypeptides that are produced either exclusively or substantially by adipocytes, play a critical and complex role, and act by endocrine, paracrine, and autocrine pathways in the malignant progression of breast cancer. Furthermore, the increased levels of leptin, resistin, and decreased adiponectin secretion are directly associated with breast cancer development. And there are also many studies indicating that adipocytokines could mediate the survival, growth, invasion, and metastasis of breast cancer cells by different cellular and molecular mechanisms to reduce the survival time and prompt the malignancy. In present review, we discuss the correlations between several adipocytokines and breast cancer cells in obesity as well as the underlying signaling pathways to provide the novel ideas for the prevention and treatment of breast cancer.


Assuntos
Adipocinas/fisiologia , Neoplasias da Mama/etiologia , Adipócitos/fisiologia , Adiponectina/fisiologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Feminino , Humanos , Leptina/fisiologia , Obesidade/complicações , Obesidade/metabolismo , Obesidade/patologia , Resistina/fisiologia
5.
Proc Natl Acad Sci U S A ; 114(42): 11027-11033, 2017 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-28973871

RESUMO

The mammalian intestine is colonized by trillions of bacteria that perform essential metabolic functions for their hosts. The mutualistic nature of this relationship depends on maintaining spatial segregation between these bacteria and the intestinal epithelial surface. This segregation is achieved in part by the presence of a dense mucus layer at the epithelial surface and by the production of antimicrobial proteins that are secreted by epithelial cells into the mucus layer. Here, we show that resistin-like molecule ß (RELMß) is a bactericidal protein that limits contact between Gram-negative bacteria and the colonic epithelial surface. Mouse and human RELMß selectively killed Gram-negative bacteria by forming size-selective pores that permeabilized bacterial membranes. In mice lacking RELMß, Proteobacteria were present in the inner mucus layer and invaded mucosal tissues. Another RELM family member, human resistin, was also bactericidal, suggesting that bactericidal activity is a conserved function of the RELM family. Our findings thus identify the RELM family as a unique family of bactericidal proteins and show that RELMß promotes host-bacterial mutualism by regulating the spatial segregation between the microbiota and the intestinal epithelium.


Assuntos
Microbioma Gastrointestinal , Bactérias Gram-Negativas , Hormônios Ectópicos/fisiologia , Mucosa Intestinal/microbiologia , Animais , Humanos , Imunidade Inata , Mucosa Intestinal/imunologia , Metabolismo dos Lipídeos , Camundongos , Resistina/fisiologia , Simbiose
6.
J Neuroendocrinol ; 29(8)2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28650080

RESUMO

Similar to leptin, resistin acts centrally to increase renal sympathetic nerve activity (RSNA). In high-fat fed animals, the sympatho-excitatory effects of leptin are retained, in contrast to the reduced actions of leptin on dietary intake. In the present study, we investigated whether the sympatho-excitatory actions of resistin were influenced by a high-fat diet. Further, because resistin and leptin combined can induce a greater sympatho-excitatory response than each alone in rats fed a normal chow diet, we investigated whether a high-fat diet (22%) could influence this centrally-mediated interaction. Mean arterial pressure (MAP), heart rate (HR) and RSNA were recorded before and for 3 hours after i.c.v. saline (control; n=5), leptin (7 µg; n=4), resistin (7 µg; n=5) and leptin and resistin combined (n=6). Leptin alone and resistin alone significantly increased RSNA (71±16%, 62±4%, respectively). When leptin and resistin were combined, there was a significantly greater increase in RSNA (195±41%) compared to either hormone alone. MAP and HR responses were not significantly different between hormones. When the responses in high-fat fed rats were compared to normal chow fed rats, there were no significant differences in the maximum RSNA responses. The findings indicate that sympatho-excitatory effects of resistin on RSNA are not altered by high-fat feeding, including the greater increase in RSNA observed when resistin and leptin are combined. Our results suggest that diets rich in fat do not induce resistance to the increase in RSNA induced by resistin alone or in combination with leptin.


Assuntos
Dieta Hiperlipídica , Rim/fisiologia , Leptina/fisiologia , Resistina/fisiologia , Sistema Nervoso Simpático/fisiologia , Animais , Pressão Arterial , Peso Corporal , Ingestão de Energia , Frequência Cardíaca , Rim/inervação , Masculino , Ratos Sprague-Dawley
7.
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
8.
Crit Care Med ; 44(7): e492-501, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26646460

RESUMO

OBJECTIVES: To assess the reversibility of acute kidney injury-induced neutrophil dysfunction and to identify involved mechanisms. DESIGN: Controlled laboratory experiment and prospective observational clinical study. SETTING: University laboratory and hospital. SUBJECTS: C57BL/6 wild-type mice. PATIENTS: Patients with septic shock with or without acute kidney injury. INTERVENTIONS: Murine acute kidney injury was induced by intraperitoneal injections of folic acid (nephrotoxic acute kidney injury) or by IM injections of glycerol (rhabdomyolysis-induced acute kidney injury). After 24 hours, we incubated isolated neutrophils for 3 hours in normal mouse serum or minimum essential medium buffer. We further studied the effects of plasma samples from 13 patients with septic shock (with or without severe acute kidney injury) on neutrophilic-differentiated NB4 cells. MEASUREMENTS AND MAIN RESULTS: Experimental acute kidney injury significantly inhibited neutrophil migration and intracellular actin polymerization. Plasma levels of resistin, a proinflammatory cytokine and uremic toxin, were significantly elevated during both forms of acute kidney injury. Incubation in serum or minimum essential medium buffer restored normal neutrophil function. Resistin by itself was able to induce acute kidney injury-like neutrophil dysfunction in vitro. Plasma resistin was significantly higher in patients with septic shock with acute kidney injury compared with patients with septic shock alone. Compared with plasma from patients with septic shock, plasma from patients with septic shock and acute kidney injury inhibited neutrophilic-differentiated NB4 cell migration. Even after 4 days of renal replacement therapy, plasma from patients with septic shock plus acute kidney injury still showed elevated resistin levels and inhibited neutrophilic-differentiated NB4 cell migration. Resistin inhibited neutrophilic-differentiated NB4 cell migration and intracellular actin polymerization at concentrations seen during acute kidney injury, but not at normal physiologic concentrations. CONCLUSIONS: Acute kidney injury-induced neutrophil dysfunction is reversible in vitro. However, standard renal replacement therapy does not correct this defect in patients with septic shock and acute kidney injury. Resistin is greatly elevated during acute kidney injury, even with ongoing renal replacement therapy, and is sufficient to cause acute kidney injury-like neutrophil dysfunction by itself.


Assuntos
Lesão Renal Aguda/fisiopatologia , Neutrófilos/fisiologia , Resistina/fisiologia , Lesão Renal Aguda/etiologia , Animais , Tampões (Química) , Técnicas de Cultura de Células , Movimento Celular , Células Cultivadas , Modelos Animais de Doenças , Glicerol , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estudos Prospectivos , Resistina/sangue , Rabdomiólise/induzido quimicamente , Choque Séptico/complicações
9.
Int J Mol Sci ; 16(12): 29370-82, 2015 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-26690142

RESUMO

A high level of serum resistin has recently been found in patients with a number of cancers, including colorectal cancer (CRC). Hence, resistin may play a role in CRC development. Fulvic acid (FA), a class of humic substances, possesses pharmacological properties. However, the effect of FA on cancer pathophysiology remains unclear. The aim of this study was to investigate the effect of resistin on the endothelial adhesion of CRC and to determine whether FA elicits an antagonistic mechanism to neutralize this resistin effect. Human HCT-116 (p53-negative) and SW-48 (p53-positive) CRC cells and human umbilical vein endothelial cells (HUVECs) were used in the experiments. Treatment of both HCT-116 and SW-48 cells with resistin increases the adhesion of both cells to HUVECs. This result indicated that p53 may not regulate this resistin effect. A mechanistic study in HCT-116 cells further showed that this resistin effect occurs via the activation of NF-κB and the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Co-treating cells with both FA and resistin revealed that FA significantly attenuated the resistin-increased NF-κB activation and ICAM-1/VCAM-1 expression and the consequent adhesion of HCT-116 cells to HUVECs. These results demonstrate the role of resistin in promoting HCT-116 cell adhesion to HUVECs and indicate that FA might be a potential candidate for the inhibition of the endothelial adhesion of CRC in response to resistin.


Assuntos
Benzopiranos/farmacologia , Neoplasias Colorretais/metabolismo , Células Endoteliais da Veia Umbilical Humana/fisiologia , Resistina/fisiologia , Adesão Celular , Quimiocinas/genética , Quimiocinas/metabolismo , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , NF-kappa B/metabolismo , Ativação Transcricional
10.
Horm Mol Biol Clin Investig ; 24(1): 25-45, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26587746

RESUMO

The increase in obesity rate is a major public health issue associated with increased pathological conditions such as type 2 diabetes or cardiovascular diseases. Obesity also contributes to decreased testosterone levels in men. Indeed, the adipose tissue is an endocrine organ which produces hormones such as leptin, adiponectin and resistin. Obesity results in pathological accumulations of leptin and resistin, whereas adiponectin plasma levels are markedly reduced, all having a negative impact on testosterone synthesis. This review focuses on current knowledge related to transcriptional regulation of Leydig cells' steroidogenesis by leptin, adiponectin and resistin. We show that there are crosstalks between the regulatory mechanisms of these hormones and androgen production which may result in a dramatic negative influence on testosterone plasma levels. Indeed leptin, adiponectin and resistin can impact expression of different steroidogenic genes such as Star, Cyp11a1 or Sf1. Further investigations will be required to better define the implications of adipose derived hormones on regulation of steroidogenic genes expression within Leydig cells under physiological as well as pathological conditions.


Assuntos
Adiponectina/fisiologia , Infertilidade Masculina/metabolismo , Leptina/fisiologia , Células Intersticiais do Testículo/fisiologia , Obesidade/metabolismo , Resistina/fisiologia , Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Índice de Massa Corporal , Regulação da Expressão Gênica , Humanos , Infertilidade Masculina/genética , Leptina/metabolismo , Masculino , Modelos Biológicos , Obesidade/genética , Obesidade/fisiopatologia , Resistina/metabolismo , Transdução de Sinais
11.
J. physiol. biochem ; 71(3): 381-390, sept. 2015.
Artigo em Inglês | IBECS | ID: ibc-142437

RESUMO

S-resistin is a non-secretable resistin spliced variant, which is expressed mainly in the white adipose tissue from Wistar rats. Previous results confirmed that 3T3-L1 cells expressing s-resistin (3T3-L1-s-res) showed an inflammatory response and exhibited a decrease in glucose transport, both basal and insulin-stimulated. Here we present evidences demonstrating for the first time that s-resistin, like resistin, blocks insulin signalling pathway by inhibiting insulin receptor, insulin receptor substrate 1, protein kinase B/Akt and the mammalian target of rapamycin phosphorylation, and increasing the suppressor of cytokine signalling 3 levels being the later probably due to augmented of leptin expression. Thus, our data suggest that s-resistin could act by a still unknown intracrine pathway as an intracellular sensor, regulating the adipocyte insulin sensitivity (AU)


No disponible


Assuntos
Animais , Ratos , Resistina/fisiologia , Insulina , Isoformas de Proteínas/análise , Adipócitos , Resistência à Insulina/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Inflamação/fisiopatologia , Mediadores da Inflamação/análise , Transdução de Sinais/fisiologia , Leptina
12.
J Physiol Biochem ; 71(3): 381-90, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26036220

RESUMO

S-resistin is a non-secretable resistin spliced variant, which is expressed mainly in the white adipose tissue from Wistar rats. Previous results confirmed that 3T3-L1 cells expressing s-resistin (3T3-L1-s-res) showed an inflammatory response and exhibited a decrease in glucose transport, both basal and insulin-stimulated. Here we present evidences demonstrating for the first time that s-resistin, like resistin, blocks insulin signalling pathway by inhibiting insulin receptor, insulin receptor substrate 1, protein kinase B/Akt and the mammalian target of rapamycin phosphorylation, and increasing the suppressor of cytokine signalling 3 levels being the later probably due to augmented of leptin expression. Thus, our data suggest that s-resistin could act by a still unknown intracrine pathway as an intracellular sensor, regulating the adipocyte insulin sensitivity.


Assuntos
Insulina/fisiologia , Resistina/fisiologia , Células 3T3-L1 , Adipogenia , Animais , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/metabolismo , Resistência à Insulina , Camundongos , Fosforilação , Isoformas de Proteínas/fisiologia , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativação Transcricional
13.
Artigo em Inglês | MEDLINE | ID: mdl-25485531

RESUMO

BACKGROUND: There is a growing interest in metabolic alterations in patients with psychiatric disorders due to their increased risk for metabolic syndrome (MetS) development. Inflammation is known to underlie the pathophysiology of schizophrenia and depression as well as MetS. Vulnerability factors for schizophrenia/depression and MetS hence appear to be shared. METHODS AND RESULTS: Based on a Web of Science search, this review examines current evidence for MetS pathophysiology involving dysregulation of adipose tissue signaling - adipokines and pro-inflammatory cytokine, both also known to be aberrant in schizophrenia/depression. Further, gender differences in the incidence and course of schizophrenia/depression were reported. The disturbances linked to the MetS are also described. Therefore, this review further maps the gender differences in the psychiatric-metabolic comorbidities. CONCLUSION: There is evidence supporting a pathological predisposition to MetS in both schizophrenia and depression in both humans and animal models. This predisposition is dramatically enhanced by antipsychotic medication. Further, there are gender differences from clinical findings suggesting women with schizophrenia/depression are more vulnerable to MetS development. This has not yet been assessed in animal studies. We suggest further validation of existing schizophrenia and depression animal models for the assessment of metabolic disturbances to provide tools for developing new antipsychotics and antidepressants with "metabolically inert" profile or improving the metabolic status in schizophrenic/depressed patients.


Assuntos
Transtorno Depressivo/complicações , Síndrome Metabólica/psicologia , Esquizofrenia/complicações , Animais , Citocinas/fisiologia , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/fisiopatologia , Masculino , Resistina/fisiologia , Caracteres Sexuais
14.
Clin Chim Acta ; 438: 46-54, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25128719

RESUMO

Adipose tissue is recognized as an endocrine organ that secretes bioactive substances known as adipokines. Excess adipose tissue and adipose tissue dysfunction lead to dysregulated adipokine production that can contribute to the development of obesity-related co-morbidities. Among the various adipokines, resistin, which was initially considered as a determinant of the emergence of insulin resistance in obesity, has appeared as an important link between obesity and inflammatory processes. Several experimental and clinical studies have suggested an association between increased resistin levels and severe conditions associated with obesity such as cardiovascular disease and malignancies. In this review, we present the growing body of evidence that human resistin is an inflammatory biomarker and potential mediator of obesity-associated diseases. A common pathway seems to involve the combined alteration of immune and inflammatory processes that favor metabolic disturbances, atherosclerosis and carcinogenesis. The mode of action and the signaling pathways utilized by resistin in its interactions with target cells could involve oxidative and nitrosative stress. Therefore, resistin could function as a key molecule in the complications of obesity development and could potentially be used as a diagnostic and prognostic marker.


Assuntos
Resistência à Insulina , Neoplasias/fisiopatologia , Resistina/fisiologia , Aterosclerose/fisiopatologia , Humanos , Inflamação/fisiopatologia , Obesidade/fisiopatologia , Transdução de Sinais
15.
J Clin Hypertens (Greenwich) ; 16(10): 754-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25186286

RESUMO

Resistant hypertension (RH) is a multifactorial disease, frequently associated with obesity and characterized by blood pressure above goal (140/90 mm Hg) despite the concurrent use of ≥3 antihypertensive drugs of different classes. The mechanisms of obesity-related hypertension include, among others, aldosterone excess and inflammatory adipokines, which have demonstrated a significant role in the pathogenesis of metabolic syndrome and RH. This review aims to summarize recent studies on the role of the adipokines leptin, resistin, and adiponectin in the pathophysiology of RH and target-organ damage associated with this condition. The deregulation of adipokine levels has been associated with clinical characteristics frequently recognized in RH such as diabetes, hyperactivity of sympathetic and renin-angiotensin-aldosterone systems, and vascular and renal damage. Strategies to regulate adipokines may be promising for the management of RH and some clinical implications must be considered when managing controlled and uncontrolled patients with RH.


Assuntos
Adipocinas/fisiologia , Anti-Hipertensivos/uso terapêutico , Resistência a Medicamentos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Adiponectina/fisiologia , Quimioterapia Combinada , Humanos , Leptina/fisiologia , Obesidade/complicações , Obesidade/fisiopatologia , Resistina/fisiologia
16.
Dis Markers ; 2014: 930206, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24692844

RESUMO

Biomarkers are highly specific and sensitive indicators of disease activity. Resistin is a recently discovered adipocytokine, having a potent biomarker quality. Initially resistin was thought to be produced by adipocytes alone; however, emerging evidence suggests that it is also produced in abundance by various cells of the immunoinflammatory system, indicating its role in various chronic inflammatory diseases. Data suggests that resistin plays a role in obesity, insulin resistance, cardiovascular diseases, and periodontitis. Resistin derived its name from the original observation that it induced insulin resistance (resist-in: resist insulin) in mice and is downregulated in mature murine adipocytes cultured in the presence of insulin sensitizing drugs like thiazolidinediones. It is well recognized that obesity, is associated with insulin resistance and diabetes. A three-way relationship has been established between diabetes, obesity and periodontitis. Recent evidence also suggests an association between obesity and increased risk for periodontitis. Our previous research showed incremental elevation of resistin with periodontal disease activity and a reduced level of resistin, after periodontal therapy. Thus resistin would be one of the molecular links connecting obesity, periodontitis, and diabetes and may serve as a marker that links periodontal disease with other systemic diseases. A Medline/PubMed search was carried out for keywords "Diabetes Mellitus," "Periodontitis," and "Resistin," and all relevant research papers from 1990 in English were shortlisted and finalized based on their importance. This review provides an insight into the biological action of resistin and its possible role in periodontitis influenced diabetes mellitus and diabetes induced periodontitis.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Periodontite/sangue , Resistina/fisiologia , Adipocinas/fisiologia , Animais , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/imunologia , Humanos , Mediadores da Inflamação/metabolismo , Obesidade/sangue , Obesidade/imunologia , Periodontite/etiologia , Periodontite/imunologia , Fatores de Risco
17.
BMC Cancer ; 14: 112, 2014 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-24555415

RESUMO

BACKGROUND: Resistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The aim of this study was to investigate the effects of resistin on HCC adhesion to the endothelium, and the mechanism underlying these resistin effects. METHODS: Human SK-Hep1 cells were used to study the effect of resistin on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions as well as NF-κB activation, and hence cell adhesion to human umbilical vein endothelial cells (HUVECs). 5-Aminoimidazole-4-carboxamide 1-ß-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, was used to determine the regulatory role of AMPK on HCC adhesion to the endothelium in regard to the resistin effects. RESULTS: Treatment with resistin increased the adhesion of SK-Hep1 cells to HUVECs and concomitantly induced NF-κB activation, as well as ICAM-1 and VCAM-1 expressions in SK-Hep1 cells. Using specific blocking antibodies and siRNAs, we found that resistin-induced SK-Hep1 cell adhesion to HUVECs was through NF-κB-regulated ICAM-1 and VCAM-1 expressions. Moreover, treatment with AICAR demonstrated that AMPK activation in SK-Hep1 cells significantly attenuates the resistin effect on SK-Hep1 cell adhesion to HUVECs. CONCLUSIONS: These results clarify the role of resistin in inducing HCC adhesion to the endothelium and demonstrate the inhibitory effect of AMPK activation under the resistin stimulation. Our findings provide a notion that resistin play an important role to promote HCC metastasis and implicate AMPK may be a therapeutic target to against HCC metastasis.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Carcinoma Hepatocelular/enzimologia , Adesão Celular/fisiologia , Neoplasias Hepáticas/enzimologia , Resistina/fisiologia , Adesão Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/enzimologia , Humanos
18.
Curr Pharm Des ; 20(31): 4961-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24320036

RESUMO

Resistin is an adipocyte- and monocyte-derived cytokine which has been implicated in the modulation of insulin action, energy, glucose and lipid homeostasis. Resistin has been associated with insulin resistance and many of its known complications. As a molecular link between metabolic signals, inflammation, and vascular dysfunction, resistin can be proposed as playing a significant role in the heightened inflammatory state induced by metabolic stress linked to excessive caloric intake, thus contributing to the risk for metabolic syndrome (MetS), type 2 diabetes (T2DM), and cardiovascular diseases (CVD). In this review, we highlighted the role of resistin, as an inflammatory cytokine, in the development of CVD, T2DM and the MetS.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Mediadores da Inflamação/fisiologia , Síndrome Metabólica/fisiopatologia , Resistina/fisiologia , Humanos , Modelos Biológicos
19.
J Hepatol ; 60(1): 87-95, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23968888

RESUMO

BACKGROUND & AIMS: This study examined whether the regulation of resistin and visfatin could reduce damage and improve regeneration in both steatotic and non-steatotic livers undergoing partial hepatectomy under ischemia-reperfusion, a procedure commonly applied in clinical practice to reduce bleeding. METHODS: Resistin and visfatin were pharmacologically modulated in lean and obese animals undergoing partial hepatectomy under ischemia-reperfusion. RESULTS: No evident role for these adipocytokines was observed in non-steatotic livers. However, obese animals undergoing liver surgery showed increased resistin in liver and plasma, without changes in adipose tissue, together with visfatin downregulation in liver and increment in plasma and adipose tissue. Endogenous resistin maintains low levels of visfatin in the liver by blocking its hepatic uptake from the circulation, thus regulating the visfatin detrimental effects on hepatic damage and regenerative failure. Indeed, the administration of anti-resistin antibodies increased hepatic accumulation of adipocyte-derived visfatin, exacerbating damage and regenerative failure. Interestingly, treatment with anti-visfatin antibodies protected steatotic livers, and similar results were obtained with the concomitant inhibition of resistin and visfatin. Thus, when visfatin was inhibited, the injurious effects of anti-resistin antibodies disappeared. Herein we show that upregulation of visfatin increased NAD levels in the remnant steatotic liver, whereas visfatin inhibition decreased them. These later observations suggest that visfatin may favour synthesis of NAD instead of DNA and induces alterations in amino acid metabolism-urea cycle and NO production, overall negatively affecting liver viability. CONCLUSIONS: Our results indicate the clinical potential of visfatin blocking-based therapies in steatotic livers undergoing partial hepatectomy with ischemia-reperfusion.


Assuntos
Citocinas/fisiologia , Fígado Gorduroso/fisiopatologia , Regeneração Hepática/fisiologia , Fígado/metabolismo , Nicotinamida Fosforribosiltransferase/fisiologia , Resistina/fisiologia , Animais , Citocinas/antagonistas & inibidores , Hepatectomia , Masculino , NAD/metabolismo , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Ratos , Ratos Wistar , Ratos Zucker , Reperfusão , Resistina/antagonistas & inibidores
20.
Med Hypotheses ; 81(6): 969-71, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24094981

RESUMO

The metabolic syndrome (MS) is a cluster of metabolic disorders arising from insulin resistance, characterized by the presence of central obesity, impaired fasting glucose level, dyslipidemia and hypertension. As the first-line medication, metformin is commonly used for MS to reduce insulin resistance. Comparing with rosiglitazone, metformin does not increase cardiovascular mortality risk in patients with MS. However, metformin is not good enough in improving insulin sensitivity. Its molecular mechanism is still not clear. Recent studies have demonstrated that resistin, an adipokine, could induce IR by both AMPK-dependent and AMPK-independent pathways. Though there were conflicting findings of resistin in metabolic syndrome or type 2 diabetes mellitus in different studies, resistin was significant decreased in the rosiglitazone treated patients than in the metformin-treated patients in most of studies. Here, we hypothesized that resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin. This hypothesis could explain why rosiglitazone is superior to metformin in enhancement of insulin sensitivity.


Assuntos
Resistência à Insulina/fisiologia , Síndrome Metabólica/tratamento farmacológico , Metformina/uso terapêutico , Resistina/fisiologia , Humanos , Metformina/metabolismo , Modelos Biológicos , Resistina/metabolismo , Rosiglitazona , Tiazolidinedionas/uso terapêutico
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