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1.
Cell Physiol Biochem ; 53(2): 355-365, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31385664

RESUMO

BACKGROUND/AIMS: NLRP3 inflammasome activation has been reported to be an early mechanism responsible for glomerular inflammation and injury in obese mice. However, the precise mechanism of obesity-induced NLRP3 inflammasome activation remains unknown. The present study explored whether adipokine visfatin mediates obesity-induced NLRP3 inflammasome activation and consequent podocyte injury. METHODS: Inflammasome formation and immunofluorescence expressions were quantified by confocal microscopy. Caspase-activity, IL-1ß production and VEGF concentrations were measured by ELISA. RESULTS: Confocal microscopic analysis showed that visfatin treatment increased the colocalization of Nlrp3 with Asc or Nlrp3 with caspase-1 in podocytes indicating the formation of NLRP3 inflammasomes. This visfatin-induced NLRP3 inflammasome formation was abolished by pretreatment of podocytes with Asc siRNA. Correspondingly, visfatin treatment significantly increased the caspase-1 activity and IL-1ß production in podocytes, which was significantly attenuated by Asc siRNA transfection. Further RT-PCR and confocal microscopic analysis demonstrated that visfatin treatment significantly decreased the podocin expression (podocyte damage). Podocytes pretreatment with Asc siRNA or caspase-1 inhibitor, WEHD attenuated this visfatin-induced podocin reduction. Furthermore, Asc siRNA transfection was found to preserve podocyte morphology by maintaining the distinct arrangement of F-actin fibers normally lost in response to visfatin. It also prevented podocyte dysfunction by restoring visfatin-induced suppression of VEGF production and secretion. CONCLUSION: Visfatin induces NLRP3 inflammasome activation in podocytes and thereby resulting in podocyte injury.


Assuntos
Adipocinas/imunologia , Inflamassomos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Nicotinamida Fosforribosiltransferase/imunologia , Podócitos/imunologia , Animais , Linhagem Celular , Inflamação/imunologia , Inflamação/patologia , Interleucina-1beta/imunologia , Camundongos , Obesidade/imunologia , Obesidade/patologia , Podócitos/citologia , Podócitos/patologia , Fator A de Crescimento do Endotélio Vascular/imunologia
2.
Nutrients ; 11(9)2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443415

RESUMO

(1) Background: Zinc is an essential micronutrient and zinc deficiency is associated with immune dysfunction. The neonatal immune system is immature, and therefore an optimal neonatal zinc status may be important. The aim of this study was to investigate the possible association between neonatal whole blood (WB)-Zinc content and several immune markers. (2) Methods: In total, 398 healthy newborns (199 who later developed type 1 diabetes and 199 controls) from the Danish Newborn Screening Biobank had neonatal dried blood spots (NDBS) analyzed for WB-Zinc content and (i) cytokines: Interleukin (IL)-1ß, IL-4, IL-6, IL-8, IL-10, IL-12 (p70), interferon gamma, tumor necrosis factor alpha, and transforming growth factor beta; (ii) adipokines: leptin and adiponectin; (iii) other immune response proteins: C-reactive protein (CRP), and mannose-binding lectin (MBL), and soluble triggering receptors expressed on myeloid cells1 (sTREM-1). WB-Zinc content was determined using laser ablation inductively coupled plasma mass spectrometry. For each analyte, the relative change in mean level was modelled by a robust log-normal model regression. (3) Results: No association was found between WB-Zinc content and all the immune response markers in either the unadjusted or adjusted models overall or when stratifying by case status. (4) Conclusions: In healthy Danish neonates, WB-Zinc content was not associated with cytokines, adipokines, CRP, MBL or sTREM, which does not indicate a strong immunological function of neonatal zinc status.


Assuntos
Adipocinas/sangue , Citocinas/sangue , Diabetes Mellitus Tipo 1/sangue , Zinco/sangue , Adipocinas/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Citocinas/imunologia , Dinamarca , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/imunologia , Teste em Amostras de Sangue Seco , Feminino , Humanos , Recém-Nascido , Masculino , Triagem Neonatal/métodos , Gravidez , Zinco/imunologia
3.
Biochem Pharmacol ; 165: 196-206, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30910694

RESUMO

Metabolic syndrome (MetS) represents a cluster of metabolic and cardiovascular complications, including obesity and visceral adiposity, insulin resistance, dyslipidemia, hyperglycemia and hypertension, which directly increase the risk of cardiovascular diseases (CVD) and diabetes mellitus type 2 (DM2). Patients with arthritic diseases, such as rheumatoid arthritis and osteoarthritis, have a higher incidence of CVD. Although recent advances in the treatment of arthritic diseases, the incidence of CVD remains elevated, and MetS has been identified as a possible link between CVD and arthritic diseases. Chronic low-grade inflammation associated with obesity has been established as a significant contributing factor to the increased prevalence of MetS. Adipokines, which play important physiological roles in metabolic activities contributing to the pathogenesis of MetS, are also involved in the regulation of autoimmune and/or inflammatory processes associated with arthritic diseases. Therefore, MetS and dysregulated secretion of pro-inflammatory adipokines have been recognized as a molecular link between CVD and arthritis diseases. In the present paper, we review recent evidence supporting the role played by adipokines, in particular leptin, adiponectin, and lipocalin-2, in the modulation of the immune system, MetS and arthritic diseases. The underlying cellular and molecular mechanisms are discussed, as well as potential new therapeutic strategies.


Assuntos
Adipocinas/metabolismo , Artrite Reumatoide/metabolismo , Sistema Imunitário/metabolismo , Síndrome Metabólica/metabolismo , Osteoartrite/metabolismo , Adipocinas/imunologia , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/imunologia , Síndrome Metabólica/imunologia , Obesidade/tratamento farmacológico , Obesidade/imunologia , Obesidade/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/imunologia
4.
Nutrients ; 11(3)2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30836628

RESUMO

(1) Background: High iron associates with inflammation and type 1 diabetes (T1D). Iron is essential not only for neonatal development but also for infectious microorganisms. The neonatal immune system is immature, and innate immunity prevails before immunocompetence develops. (2) Methods: In 398 newborns from the Danish Newborn Screening Biobank, we examined if whole blood iron (WB-Iron) content were associated with cytokines, adipokines, C-reactive protein (CRP), and mannose-binding lectin (MBL) in non-infected healthy neonates, and if these associations differed in newborns who later developed T1D (cases) (n = 199). WB-Iron was quantified using laser ablation inductively coupled plasma mass spectrometry on the neonatal dried blood spots. For each analyte, the relative change (RC) in the mean level was modeled by robust log-normal regression. (3) Results: A one unit increase in neonatal WB-Iron was associated with a 38% decrease in mean interleukin (IL)-6 levels (0.62; 95% CI: 0.40⁻0.95, p = 0.03), and a 37% decrease in mean MBL levels (0.63; 95% CI: 0.41⁻0.95, p = 0.03), but was not statistically significant after correction for multiple testing. (4) Conclusions: In summary, we found that higher neonatal WB-iron content was inversely associated with IL-6 and MBL, which may increase susceptibility to infections.


Assuntos
Adipocinas/sangue , Citocinas/sangue , Doenças do Recém-Nascido/imunologia , Ferro/sangue , Lectina de Ligação a Manose/sangue , Adipocinas/imunologia , Bancos de Espécimes Biológicos , Biomarcadores/sangue , Proteína C-Reativa/análise , Proteína C-Reativa/imunologia , Citocinas/imunologia , Dinamarca , Diabetes Mellitus Tipo 1/sangue , Feminino , Voluntários Saudáveis , Humanos , Imunidade Inata/imunologia , Recém-Nascido , Doenças do Recém-Nascido/sangue , Interleucina-6/sangue , Interleucina-6/imunologia , Ferro/imunologia , Masculino , Lectina de Ligação a Manose/imunologia , Análise de Regressão
5.
Pharmacol Rep ; 71(1): 105-111, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30513401

RESUMO

Crohn's disease (CD) is a chronic, immune system-mediated inflammatory disease affecting gastrointestinal (GI) tract. The pathogenesis of the intestinal lesions is not entirely explained and understood: excessive activation of the immune system may come as a result of the interaction of environmental, genetic and infectious factors and the mediation of abnormal intestinal flora. The main objective of the current study is to further identify the role of adipose tissue in the pathogenesis of CD. Alterations in body fat distribution, accumulation of intra-abdominal white adipose tissue (WAT) and mesenteric obesity are well-known features of CD. Up to date, data concerning the role of WAT in the pathogenesis of CD is limited with only a few studies on the relationship between WAT and the course of the disease, as well as pro- and anti-inflammatory cytokine profile and general immune system functioning. In this review, we focus on the importance of physiological and pathophysiological WAT functions and secreted adipokines, which seem to have a vital role in the inflammatory and fibrotic processes in CD sufferers.


Assuntos
Adipocinas/metabolismo , Tecido Adiposo Branco/metabolismo , Doença de Crohn/metabolismo , Intestinos , Obesidade/metabolismo , Adipocinas/imunologia , Tecido Adiposo Branco/imunologia , Tecido Adiposo Branco/fisiopatologia , Adiposidade , Animais , Doença de Crohn/imunologia , Doença de Crohn/microbiologia , Doença de Crohn/fisiopatologia , Microbioma Gastrointestinal , Humanos , Mediadores da Inflamação/metabolismo , Intestinos/imunologia , Intestinos/microbiologia , Intestinos/fisiopatologia , Obesidade/imunologia , Obesidade/microbiologia , Obesidade/fisiopatologia , Transdução de Sinais
6.
Front Immunol ; 9: 2133, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30294325

RESUMO

Background and aims: Chronic ethanol exposure results in inflammation in adipose tissue; this response is associated with activation of complement as well as the development of alcohol-related liver disease (ALD). Adipose communicates with other organs, including liver, via the release of soluble mediators, such as adipokines and cytokines, characterized as the "adipose secretome." Here we investigated the role of the anaphaylatoxin receptors C3aR and C5aR1 in the development of adipose tissue inflammation and regulation of the adipose secretome in murine ALD (mALD). Methods: Wild-type C57BL/6 (WT), C3aR -/-, and C5aR1 -/- mice were fed Lieber-DeCarli ethanol diet for 25 days (6% v/v, 32% kcal) or isocaloric control diets; indicators of inflammation and injury were assessed in gonadal adipose tissue. The adipose secretome was characterized in isolated adipocytes and stromal vascular cells. Results: Ethanol feeding increased the expression of adipokines, chemokines and leukocyte markers in gonadal adipose tissue from WT mice; C3aR -/- were partially protected while C5aR1 -/- mice were completely protected. In contrast, induction of CYP2E1 and accumulation of TUNEL-positive cells in adipose in response to ethanol feeding was independent of genotype. Bone marrow chimeras, generated with WT and C5aR1 -/- mice, revealed C5aR1 expression on non-myeloid cells, likely to be adipocytes, contributed to ethanol-induced adipose inflammation. Chronic ethanol feeding regulated both the quantity and distribution of adipokines secreted from adipocytes in a C5aR1-dependent mechanism. In WT mice, chronic ethanol feeding induced a predominant release of pro-inflammatory adipokines from adipocytes, while the adipose secretome from C5aR1 -/- mice was characterized by an anti-inflammatory/protective profile. Further, the cargo of adipocyte-derived extracellular vesicles (EVs) was distinct from the soluble secretome; in WT EVs, ethanol increased the abundance of pro-inflammatory mediators while EV cargo from C5aR1 -/- adipocytes contained a greater diversity and more robust expression of adipokines. Conclusions: C3aR and C5aR1 are potent regulators of ethanol-induced adipose inflammation in mALD. C5aR1 modulated the impact of chronic ethanol on the content of the adipose secretome, as well as influencing the cargo of an extensive array of adipokines from adipocyte-derived EVs. Taken together, our data demonstrate that C5aR1 contributes to ethanol-mediated changes in the adipose secretome, likely contributing to intra-organ injury in ALD.


Assuntos
Tecido Adiposo/metabolismo , Etanol/efeitos adversos , Hepatopatias Alcoólicas/imunologia , Receptor da Anafilatoxina C5a/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Adipócitos , Adipocinas/imunologia , Adipocinas/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/imunologia , Anafilatoxinas/imunologia , Anafilatoxinas/metabolismo , Animais , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Etanol/administração & dosagem , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/metabolismo , Feminino , Fígado/imunologia , Fígado/metabolismo , Hepatopatias Alcoólicas/etiologia , Hepatopatias Alcoólicas/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Cultura Primária de Células , Receptor da Anafilatoxina C5a/genética , Receptor da Anafilatoxina C5a/imunologia , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/imunologia
7.
J Reprod Immunol ; 130: 25-29, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30174020

RESUMO

The detrimental consequences of obesity on female fertility are well known, but the functional changes that occur in the ovary in response to elevated BMI are not clear. Obesity induces multiple components of a systemic inflammatory state that is a key pathway by which it initiates tissue dysfunction in adipose, liver and muscle; however whether obesity induces similar inflammatory changes in the ovary has not been fully investigated. This is important to understand because it is increasingly clear that obesity at conception impacts not only pregnancy rates but also influences pre-implantation embryo development. To further understand the characteristics of inflammation in the ovaries of obese women we analysed a panel of cytokines (IL6, IL10 and TNFα), adipokines (adiponectin, leptin and monocyte chemotactic factor 1 (MCP-1)) and acute phase proteins (C-Reactive Protein (CRP) and sICAM-1) in the ovarian follicular fluid obtained at oocyte aspiration from women (n = 48) who were lean, overweight or obese. We hypothesised that adipokines and pro-inflammatory cytokines would be correlated with and/or dysregulated by increasing Body Mass Index (BMI). Surprisingly however, the majority were not related to BMI but instead were positively correlated with lipid levels in follicular fluid, namely triglycerides and free fatty acids. Further, as is typical of metabolic inflammation, the inflammatory markers that were associated with intra-follicular lipids included both pro-inflammatory (CRP, IL6, TNFα) and anti-inflammatory (adiponectin, IL10) mediators. The direct consequences of an ovarian microenvironment containing high levels of lipids and inflammatory mediators are not known but could impact luteinisation, ovulation and/or oocyte developmental competence.


Assuntos
Ácidos Graxos não Esterificados/metabolismo , Líquido Folicular/química , Inflamação/imunologia , Obesidade/imunologia , Triglicerídeos/metabolismo , Adipocinas/análise , Adipocinas/imunologia , Adipocinas/metabolismo , Biomarcadores/análise , Biomarcadores/metabolismo , Índice de Massa Corporal , Proteína C-Reativa/análise , Proteína C-Reativa/imunologia , Proteína C-Reativa/metabolismo , Citocinas/análise , Citocinas/imunologia , Citocinas/metabolismo , Ácidos Graxos não Esterificados/análise , Feminino , Líquido Folicular/imunologia , Humanos , Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/análise , Molécula 1 de Adesão Intercelular/imunologia , Molécula 1 de Adesão Intercelular/metabolismo , Obesidade/metabolismo , Triglicerídeos/análise
8.
Arch Pharm Res ; 41(11): 1062-1073, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30264324

RESUMO

Adipose tissue acts as a dynamic endocrine organ playing critical roles in many metabolic and immune responses. Endocrine functions by adipose tissue are achieved by secretion of diverse cytokines and hormones, collectively called adipokines. Adiponectin and leptin the most abundantly expressed adipokines within adipose tissue have an impact on various physiological responses. While both adiponectin and leptin are secreted from the same location, their physiological functions are not identical. Adiponectin possesses potent anti-inflammatory properties and anti-tumor activities, whereas leptin acts as a pro-inflammatory hormone and generates tumor-promoting effects. Autophagy, a highly conserved intracellular self-digestive process, is implicated in the maintenance of diverse physiological responses. In particular, autophagy plays dual roles in the regulation of cell death/survival (e.g., inducing cell death and cytoprotection) and is associated with anti-inflammatory actions. Increasing recent evidence has indicated that autophagy is implicated in various biological responses by adipokines. Therefore, autophagy would be a promising target for the management of inflammation and tumor growth by adipokines. In this review, we summarize the effects of adiponectin and leptin on autophagy induction and highlight their implications in modulating inflammatory responses and tumor growth.


Assuntos
Adipocinas/imunologia , Tecido Adiposo , Autofagia/imunologia , Tecido Adiposo/imunologia , Tecido Adiposo/patologia , Animais , Morte Celular/imunologia , Sobrevivência Celular/imunologia , Humanos , Inflamação , Obesidade/imunologia , Obesidade/patologia , Especificidade de Órgãos
9.
Biochim Biophys Acta Mol Basis Dis ; 1864(11): 3805-3823, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30251697

RESUMO

Type 2 diabetes has traditionally been viewed as a metabolic disorder characterised by chronic high glucose levels, insulin resistance, and declining insulin secretion from the pancreas. Modern lifestyle, with abundant nutrient supply and reduced physical activity, has resulted in dramatic increases in the rates of obesity-associated disease conditions, including diabetes. The associated excess of nutrients induces a state of systemic low-grade chronic inflammation that results from production and secretion of inflammatory mediators from the expanded pool of activated adipocytes. Here, we review the mechanisms by which obesity induces adipose tissue dysregulation, detailing the roles of adipose tissue secreted factors and their action upon other cells and tissues central to glucose homeostasis and type 2 diabetes. Furthermore, given the emerging importance of adipokines, cytokines and chemokines in disease progression, we suggest that type 2 diabetes should now be viewed as an autoinflammatory disease, albeit one that is driven by metabolic dysregulation.


Assuntos
Tecido Adiposo/imunologia , Diabetes Mellitus Tipo 2/imunologia , Inflamação/imunologia , Obesidade/metabolismo , Estresse Fisiológico/imunologia , Adipocinas/imunologia , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Humanos , Inflamação/metabolismo , Resistência à Insulina/imunologia , Obesidade/imunologia
10.
Endocrinology ; 159(11): 3801-3812, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30215698

RESUMO

The rates of obesity and diabetes are increasing worldwide, whereas the age of onset for both obesity and diabetes are decreasing steadily. Obesity and diabetes are associated with multiple factors that contribute to the increased risk of a number of different cancers, including breast cancer. These factors are hyperinsulinemia, elevated IGFs, hyperglycemia, dyslipidemia, adipokines, inflammatory cytokines, and the gut microbiome. In this review, we discuss the current understanding of the complex signaling pathways underlying these multiple factors involved in the obesity/diabetes-breast cancer link, with a focus particularly on the roles of the insulin/IGF system and dyslipidemia in preclinical breast cancer models. We review some of the therapeutic strategies to target these metabolic derangements in cancer. Future research directions and potential therapeutic strategies are also discussed.


Assuntos
Neoplasias da Mama/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/metabolismo , Adipocinas/imunologia , Tecido Adiposo/metabolismo , Animais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/imunologia , Citocinas/imunologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/imunologia , Dislipidemias/metabolismo , Feminino , Microbioma Gastrointestinal , Humanos , Hiperglicemia/metabolismo , Hiperinsulinismo/metabolismo , Inflamação/imunologia , Insulina/metabolismo , Obesidade/epidemiologia , Obesidade/imunologia , Fatores de Risco , Somatomedinas/metabolismo
11.
PLoS One ; 13(9): e0204180, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30212581

RESUMO

Meteorin-like (Metrnl) is a newly discovered adipokine with favorable effect on insulin sensitivity. Previous studies have reported lower levels of Metrnl in obese patients. However, there is conflicting data regarding its circulating levels in type 2 diabetes mellitus (T2DM) and there is no data in patients with coronary artery disease (CAD). The aim of the present study was to evaluate the Metrnl serum level in patients with T2DM and CAD, and also to evaluate the serum levels of Metrnl with serum levels of adiponectin, IL-6 and TNF-α in patients. This study was conducted on 66 patients with CAD, 63 T2DM patients and 41 controls. The serum levels of Metrnl, adiponectin, IL-6 and TNF-α were measured using ELISA techniques. The serum levels of Metrnl were found to be lower in CAD (75.18 ± 28.48 pg/mL) and T2DM patients (73.89 ± 33.60 pg/mL) compared to the control group (95.33 ± 32.56 pg/mL) (p < 0.005 and p<0.003, respectively). Additionally, adiponectin decreased in CAD and T2DM patients as compared to the control group, while IL-6 and TNF-α were higher in CAD and T2DM patients. Metrnl showed independent association with the risk of CAD and T2DM presence. Furthermore, Metrnl illustrated a negative correlation with IL-6 and TNF-α in both CAD patients and also with BMI, insulin resistance, IL-6 and TNF-α in T2DM patients. Metrnl showed an association with CAD and T2DM presence and with components of their pathogenesis such as inflammation and insulin resistance. These results suggested a possible interaction between Metrnl and the pathogenesis of CAD and T2DM, however more studies are needed to prove this concept.


Assuntos
Adipocinas/genética , Adiponectina/genética , Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/genética , Resistência à Insulina/genética , Interleucina-6/genética , Fator de Necrose Tumoral alfa/genética , Adipocinas/sangue , Adipocinas/imunologia , Adiponectina/sangue , Adiponectina/imunologia , Idoso , Glicemia/metabolismo , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/imunologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/imunologia , Feminino , Expressão Gênica , Humanos , Inflamação , Resistência à Insulina/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia
12.
Eur J Clin Invest ; 48(9): e12997, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29995306

RESUMO

Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including type 2 diabetes, cardiovascular diseases, nonalcoholic fatty liver disease and cancer. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins and growth and vasoactive factors, collectively termed adipokines that influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodelling and fibrosis together with an altered secretion of adipokines. This review describes how adipose tissue becomes inflamed in obesity and summarizes key players and molecular mechanisms involved in adipose inflammation.


Assuntos
Adipocinas/imunologia , Inflamação/imunologia , Gordura Intra-Abdominal/imunologia , Obesidade/imunologia , Adipocinas/metabolismo , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Humanos , Inflamação/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo
13.
Horm Mol Biol Clin Investig ; 33(2)2018 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-29547393

RESUMO

Obesity and associated metabolic co-morbidities are a worldwide public health problem. Negative health outcomes associated with obesity, however, do not arise from excessive adiposity alone. Rather, deleterious outcomes of adipose tissue accumulation are a result of how adipocytes are distributed to individual regions in the body. Due to our increased understanding of the dynamic relationship that exists between specific adipose depots and disease risk, an accurate characterization of total body adiposity as well as location is required to properly evaluate a population's disease risk. Specifically, distinctive tissue depots within the body include the lower body, upper body and abdominal (deep and superficial) subcutaneous regions, as well as visceral (mesenteric and omental) regions. Upper body and visceral adipose tissues are highly associated with metabolic dysfunction and chronic disease development, whereas lower body gluteofemoral subcutaneous adipose tissue imparts protection against diet-induced metabolic derangement. Each adipose depot functions distinctly as an endocrine organ hence it has a different level of impact on health outcomes. Effluent from adipose tissue can modulate the functions of other tissues, whilst receiving differential communication from the rest of the body via central nervous system innervation, metabolites and other signaling molecules. More so, adipose depots contain a diverse reservoir of tissue-resident immune cells that play an integral part in both maintaining tissue homeostasis, as well as propagating metabolically-induced inflammation. Overall, the conceptualization of obesity and associated risks needs updating to reflect the complexities of obesity. We review adipose tissue characteristics that are linked to deleterious or beneficial adipose tissue distributions.


Assuntos
Tecido Adiposo/patologia , Obesidade/complicações , Obesidade/patologia , Adipocinas/análise , Adipocinas/imunologia , Adipocinas/metabolismo , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Adiposidade , Animais , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Diabetes Mellitus/etiologia , Diabetes Mellitus/imunologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Humanos , Imunidade Celular , Inflamação/etiologia , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Obesidade/imunologia , Obesidade/metabolismo
14.
Clin Exp Pharmacol Physiol ; 45(8): 819-831, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29569260

RESUMO

Non-alcoholic fatty liver disease (NAFLD) has been considered as a multi-factorial metabolic syndrome. MicroRNA-375 (MiR-375) was significantly up-regulated in serum of NAFLD patients and the role of miR-375 was addressed as a putative biomarker of NAFLD progression. However, the specific function of miR-375 in the progression of NAFLD is still unclear and the molecular mechanisms underlying NAFLD have yet to be elucidated. Our study aimed at investigating the regulatory role of miR-375 in the molecular mechanisms of the pathogenic progression of NAFLD and to find out whether miR-375 regulates the expression level of adipokines and inflammatory cytokines in NAFLD. We found that miR-375 expression was increased in the serum of high fat diet (HFD)-feeding mice comparing to that in healthy controls, whereas the expression of Adiponectin receptor 2 (AdipoR2) was decreased in mice fed with HFD. Moreover, inhibiton of miR-375 up-regulated the expression of Adiponectin, inhibited the lipid accumulation and down-regulated both the level of Leptin and inflammatory cytokines including tumour necrosis factor (TNF)-α and interleukin (IL)-6 in palmiticacid (PA)-induced human hepatocellular carcinoma HepG2 cells. In addition, we also found that AdipoR2 was a target of miR-375 by binding directly to the 3'UTR of it. Of note, the reduced level of TNF-α, IL-6 as well as Leptin and the production of Adiponectin by miR-375 inhibitors was significantly reversed by silencing of AdipoR2 in PA-induced HepG2 cells. Our findings bring new insight into understanding the complex mechanisms underlying the pathogenesis of NAFLD and provide evidence that miR-375 might represent a novel therapeutic target for NAFLD.


Assuntos
Adipocinas/metabolismo , Citocinas/metabolismo , MicroRNAs/sangue , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/sangue , Receptores de Adiponectina/metabolismo , Adipocinas/imunologia , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Regulação para Baixo , Células Hep G2 , Humanos , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácido Palmítico/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
15.
Georgian Med News ; (274): 116-124, 2018 Jan.
Artigo em Russo | MEDLINE | ID: mdl-29461239

RESUMO

In addition to accumulation and metabolism of triglycerides, white adipose tissue is recognized as the active endocrine organ, whose dysfunction is associated with the development of a wide range of diseases. The secretome of adipocytes is represented by a wide range of adipokines, which vary in depot and sex-specific manner. In addition, adipokines have diverse biological effects, correlations with different metabolic features and functions. In this review, the data on biological effects, origin and the clinical significance of adipokines are discussed. The influence of adipokines on metabolism, sensitivity to insulin, vascular homeostasis, angiogenesis, repair, inflammation and immune cells are shown. Visceral adipose tissue accumulation is accompanied with adipocytes hypertrophy and overproduction of such proinflammatory and proaterogenic molecules like resistin, visfatin, vaspin, tumor necrosis factor, interleukin 6, lipocalin, glypican 4, RBP4 etc. There is a tight correlation between these adipokines level and development of insulin resistance, type 2 diabetes, cardiometabolic complications and cancer. Thus, adipokines represent a group of informative biomarkers for the diagnostics of metabolic disorders and the prediction of the outcome of the wide range of diseases. The study of the effects and mechanisms of the action of adipokines is the basis for determining new targets for therapy.


Assuntos
Adipócitos Brancos/metabolismo , Adipocinas/genética , Tecido Adiposo Branco/metabolismo , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Neoplasias/metabolismo , Adipócitos Brancos/citologia , Adipócitos Brancos/imunologia , Adipocinas/imunologia , Tecido Adiposo Branco/citologia , Tecido Adiposo Branco/imunologia , Biomarcadores/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/patologia , Regulação da Expressão Gênica , Humanos , Resistência à Insulina , Metaboloma/imunologia , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Neovascularização Fisiológica/imunologia , Fatores Sexuais , Transdução de Sinais , Triglicerídeos/imunologia , Triglicerídeos/metabolismo
16.
Br J Pharmacol ; 175(10): 1569-1579, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29486050

RESUMO

Obesity has reached epidemic proportions in the Western society and is increasing in the developing world. It is considered as one of the major contributors to the global burden of disability and chronic diseases, including autoimmune, inflammatory and degenerative diseases. Research conducted on obesity and its complications over the last two decades has transformed the outdated concept of white adipose tissue (WAT) merely serving as an energy depot. WAT is now recognized as an active and inflammatory organ capable of producing a wide variety of factors known as adipokines. These molecules participate through endocrine, paracrine, autocrine or juxtacrine crosstalk mechanisms in a great variety of physiological or pathophysiological processes, regulating food intake, insulin sensitivity, immunity and inflammation. Although initially restricted to metabolic activities (regulation of glucose and lipid metabolism), adipokines currently represent a new family of proteins that can be considered key players in the complex network of soluble mediators involved in the pathophysiology of immune/inflammatory diseases. However, the complexity of the adipokine network in the pathogenesis and progression of inflammatory diseases has posed, since the beginning, the important question of whether it may be possible to target the mechanism(s) by which adipokines contribute to disease selectively without suppressing their physiological functions. Here, we explore in depth the most recent findings concerning the involvement of adipokines in inflammation and immune responses, in particular in rheumatic, inflammatory and degenerative diseases. We also highlight several possible strategies for therapeutic development and propose that adipokines and their signalling pathways may represent innovative therapeutic strategies for inflammatory disorders.


Assuntos
Adipocinas/imunologia , Inflamação/complicações , Inflamação/imunologia , Obesidade/complicações , Animais , Humanos , Obesidade/imunologia , Obesidade/patologia
17.
J Asthma ; 55(6): 579-587, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28771382

RESUMO

OBJECTIVE: Adipokines are correlated with immune responses in asthma, but data on the roles of chemerin and omentin in asthma are limited. This study explored the relationship of chemerin and omentin levels with Th17 and Th9 cells in asthma. METHODS: Seventy-six asthmatics were divided into intermittent-to-mild persistent (n  =  28), moderate persistent (n  =  26) and severe persistent (n  =  22) and were enrolled in the study. Additionally, 20 healthy subjects were enrolled as controls. Clinical characteristics of the subjects, the Asthma Control Test, lung function, fractional exhaled nitric oxide score, and plasma chemerin and omentin levels were evaluated, and the percentages of Th17 and Th9 cells were determined by flow cytometry. RESULTS: The percentages of Th17 and Th9 cells were higher in the moderate-to-severe persistent asthmatics than in the intermittent-to-mild persistent asthmatics or healthy controls (p < 0.05). The severe persistent asthma group had a higher chemerin level but lower omentin levels than the control group (p < 0.05). Chemerin levels were positively correlated with Th17 and Th9 cell percentages, while omentin levels were negatively correlated with Th17 and Th9 cell percentages (p < 0.01). CONCLUSIONS: The regulatory functions of adipokines on immune responses may be associated with pathogenesis and processes of asthma.


Assuntos
Adipocinas/sangue , Asma/imunologia , Quimiocinas/sangue , Citocinas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Lectinas/sangue , Células Th17/imunologia , Adipocinas/imunologia , Adulto , Idoso , Asma/sangue , Asma/diagnóstico , Quimiocinas/imunologia , Estudos Transversais , Citocinas/imunologia , Feminino , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/imunologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Interleucina-9/imunologia , Interleucina-9/metabolismo , Lectinas/imunologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
18.
Chin J Nat Med ; 15(9): 664-673, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28991527

RESUMO

Adipose tissue hypoxia has been recognized as the initiation of insulin resistance syndromes. The aim of the present study was to investigate the effects of mangiferin on the insulin signaling pathway and explore whether mangiferin could ameliorate insulin resistance caused by hypoxia in adipose tissue. Differentiated 3T3-L1 adipocytes were incubated under normal and hypoxic conditions, respectively. Protein expressions were analyzed by Western blotting. Inflammatory cytokines and HIF-1-dependent genes were tested by ELISA and q-PCR, respectively. The glucose uptake was detected by fluorescence microscopy. HIF-1α was abundantly expressed during 8 h of hypoxic incubation. Inflammatory reaction was activated by up-regulated NF-κB phosphorylation and released cytokines like IL-6 and TNF-α. Glucose uptake was inhibited and insulin signaling pathway was damaged as well. Mangiferin substantially inhibited the expression of HIF-1α. Lactate acid and lipolysis, products released by glycometabolism and lipolysis, were also inhibited. The expression of inflammatory cytokines was significantly reduced and the damaged insulin signaling pathway was restored to proper functional level. The glucose uptake of hypoxic adipocytes was promoted and the dysfunction of adipocytes was relieved. These results showed that mangiferin could not only improve the damaged insulin signaling pathway in hypoxic adipocytes, but also ameliorate inflammatory reaction and insulin resistance caused by hypoxia.


Assuntos
Adipócitos/efeitos dos fármacos , Adipocinas/genética , Resistência à Insulina , Oxigênio/metabolismo , Xantonas/farmacologia , Células 3T3-L1 , Adipócitos/imunologia , Adipocinas/imunologia , Animais , Hipóxia Celular/efeitos dos fármacos , Glucose/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/imunologia , Insulina/metabolismo , Camundongos , NF-kappa B/genética , NF-kappa B/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
19.
Biochem Biophys Res Commun ; 494(3-4): 648-655, 2017 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-29079192

RESUMO

A large amount of fructose intake along with smoking is associated with increased incidence of diseases linked to metabolic syndrome. More research is necessary to understand the complex mechanism that ultimately results in metabolic syndrome and the effect, if any, of high fructose dietary intake and smoking on individual health. In this study, we investigated changes in ER-Golgi network and disturbance to secretion of adipokines induced by cigarette smoking (CS) and excess fructose intake and their contribution to the disruption of metabolic homeostasis. We used high fructose-induced metabolic disorder mice model by feeding them with high fructose diet for 8 weeks. For CS exposure experiment, these mice were exposed to CS for 28 days according to OECD guideline 412. Our results clearly showed that the immune system was suppressed and ER stress was induced in mice with exposure to CS and fed with high fructose. Furthermore, their concentrations of adipokines including leptin and adiponectin were aberrant. Such alteration in secretion of adipokines could cause insulin resistance which may lead to the development of type 2 diabetes.


Assuntos
Adipocinas/imunologia , Adipocinas/metabolismo , Apoptose/efeitos dos fármacos , Fumar Cigarros/efeitos adversos , Resistência à Insulina/imunologia , Doenças Metabólicas/imunologia , Animais , Açúcares da Dieta , Frutose , Masculino , Doenças Metabólicas/induzido quimicamente , Camundongos , Camundongos Endogâmicos C57BL , Poluição por Fumaça de Tabaco/efeitos adversos
20.
Adv Neurobiol ; 19: 191-210, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28933066

RESUMO

Since the discovery of the remarkable properties of adipose tissue as a metabolically active organ, several evidences on the possible link between obesity and the pathogenesis of multiple sclerosis (MS) have been gathered. Obesity in early life, mainly during adolescence, has been proposed as a relevant risk factor for late MS development. Moreover, once MS is initiated, obesity can contribute to increase disease severity by negatively influencing disease progress. Despite the fact that clinical data are not yet conclusive, many biochemical links have been recently disclosed. The "low-grade inflammation" that characterizes obesity can lead to neuroinflammation through different mechanisms, including choroid plexus and blood-brain barrier disruption. Furthermore, it is well known that resident immune cells of central nervous system and peripheral immune cells are involved in the pathogenesis of MS, and adipokines and neuropeptides such as neuropeptide Y may mediate the cross talk between them.


Assuntos
Adipocinas/imunologia , Inflamação/imunologia , Esclerose Múltipla/imunologia , Obesidade/imunologia , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo , Plexo Corióideo/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/imunologia , Humanos , Hidroxietilrutosídeo , Inflamação/metabolismo , Esclerose Múltipla/metabolismo , Neuropeptídeo Y/imunologia , Obesidade/metabolismo
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