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1.
Asian Pac J Cancer Prev ; 21(3): 599-609, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32212784

RESUMO

BACKGROUND: Adipokines play an important role in the regulation of inflammation and tumor progression. AIM: Assessment of the possible role of adiponectin, leptin and visfatin in HCV associated hepatocellular carcinoma (HCC). METHODS: patients were classified into 85 patients with HCV associated HCC, 100 patients with chronic hepatitis C viral (HCV) infection compared to 50 normal control (NC) subjects. All subjects included in the study were assessed for HCV infection by seropositive HCV antibodies, as well as HCV RNA by RT-PCR. Serum levels of adiponectin, leptin and visfatin were assessed using enzyme linked immunosorbent assay (ELISA). The data were correlated to the relevant clinic-pathological features of the patients, and the overall survival (OS) rate. RESULTS: There was a significant difference in the serum levels of adiponectin and visfatin among HCC, HCV and NC groups (P<0.001). The serum levels of leptin and alpha fetoprotein (AFP) were significantly higher in HCC group (P<0.001). There was a significant association between the serum level of adiponectin and advanced Child class liver cirrhosis (P=0.03), as well as with poor performance status (ECOG, P=0.02). Serum leptin associated significantly with the number of lesions in the liver (P=0.006), visfatin associated with increased mortality rate (P<0.001). Adiponectin, leptin and visfatin associated significantly with liver cirrhosis in HCV patients (P<0.01). Leptin achieved the highest sensitivity (98.8%). visfatin achieved the highest specificity (100%) and PPV (100%) for detection of HCC. The combination of serum leptin and visfatin for the diagnosis of HCV associated HCC showed sensitivity, specificity, PPV, NPV and accuracy (100%, 96.6%, 93.4%, 100% and 97.4%; respectively). CONCLUSION: Adiponectin, leptin and visfatin have an important role(s) in the pathogenesis of HCV associated HCC. 
.


Assuntos
Adipocinas/metabolismo , Carcinoma Hepatocelular/metabolismo , Hepatite C/complicações , Neoplasias Hepáticas/metabolismo , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/virologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/sangue
2.
Adv Clin Chem ; 94: 261-321, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31952573

RESUMO

Studies have linked obesity, metabolic syndrome, type 2 diabetes, cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD) and dementia. Their relationship to the incidence and progression of these disease states suggests an interconnected pathogenesis involving chronic low-grade inflammation and oxidative stress. Metabolic syndrome represents comorbidities of central obesity, insulin resistance, dyslipidemia, hypertension and hyperglycemia associated with increased risk of type 2 diabetes, NAFLD, atherosclerotic CVD and neurodegenerative disease. As the socioeconomic burden for these diseases has grown signficantly with an increasing elderly population, new and alternative pharmacologic solutions for these cardiometabolic diseases are required. Adipose tissue, skeletal muscle and liver are central endocrine organs that regulate inflammation, energy and metabolic homeostasis, and the neuroendocrine axis through synthesis and secretion of adipokines, myokines, and hepatokines, respectively. These organokines affect each other and communicate through various endocrine, paracrine and autocrine pathways. The ultimate goal of this review is to provide a comprehensive understanding of organ crosstalk. This will include the roles of novel organokines in normal physiologic regulation and their pathophysiological effect in obesity, metabolic syndrome, type 2 diabetes, CVD, NAFLD and neurodegenerative disorders.


Assuntos
Adipocinas/metabolismo , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Síndrome Metabólica/metabolismo , Doenças Neurodegenerativas/metabolismo , Obesidade/metabolismo , Humanos
3.
Anticancer Res ; 39(12): 6653-6660, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810930

RESUMO

AIM: The aim of this study was to investigate the effects of medium-chain triglycerides (MCTs) on chemically-induced hepatic carcinogenesis (HCC) in mice. MATERIALS AND METHODS: In a first set of experiments, mice were treated with diethylnitrosoamine intraperitoneally at two weeks of age. They were fed chow containing MCT or a normal chow diet and sacrificed after 28 weeks. Incidence of hepatic tumor was compared between the two groups. Expression of oxidative stress, and inflammatory cytokines and chemokines in liver tissues were examined. In a second set of experiments, the histopathological findings of the intraperitoneal adipose tissue were assessed, and expression of adipocytokines in the fat tissue was measured. In a third set of experiments, plasma ß-hydroxybutyrate (HB) concentration was measured in both animals fed chow containing MCT and a normal chow diet. Mouse HCC cells were co-cultured with ß-HB, and the numbers of tumor cells were counted at days 3 and 7. RESULTS: In the first set of experiments, the tumor count observed in the control group was significantly blunted in the MCT group. Maximum tumor diameter also decreased in the MCT group compared to the control group. The expression of inflammatory cytokines and chemokines was significantly decreased by MCT. Furthermore, expression of 4-hydroxynonenal was lower in the MCT group compared to the control group. In the second set of experiments, hypertrophy of the adipocytes was suppressed, and the concentration of adiponectin and leptin in the adipose tissue decreased by MCT. In the third set of experiments, plasma ß-HB concentration increased in the MCT group as expected. ß-HB significantly inhibited the proliferation of HCC cells. CONCLUSION: MCT administration markedly suppresses the incidence of chemically-induced HCC by inhibition of inflammation and increase of ketone bodies.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Carcinoma Hepatocelular/prevenção & controle , Neoplasias Hepáticas Experimentais/prevenção & controle , Triglicerídeos/farmacologia , Ácido 3-Hidroxibutírico/sangue , Adipócitos/patologia , Adipocinas/metabolismo , Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Aldeídos/metabolismo , Ração Animal/análise , Animais , Carcinógenos , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Contagem de Células , Proliferação de Células , Quimiocinas/metabolismo , Citocinas/metabolismo , Dietilnitrosamina , Hipertrofia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Leptina/metabolismo , Fígado/metabolismo , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Estresse Oxidativo , Triglicerídeos/administração & dosagem
4.
Orv Hetil ; 160(44): 1727-1734, 2019 Nov.
Artigo em Húngaro | MEDLINE | ID: mdl-31657254

RESUMO

Authors discuss the musculoskeletal aspects of obesity by applying a novel approach. Biochemical changes associated with obesity and especially metabolic syndrome, may have a great impact on the function of bones, joints and muscles. Therefore we need a new view and new strategies in rheumatic diseases. Obesity-associated metabolic changes should be considered during the progress of as well as the selection of treatment in inflammatory rheumatic diseases. Individualised treatment is necessary due to associated comorbidities as well. Orv Hetil. 2019; 160(44): 1727-1734.


Assuntos
Artropatias/etiologia , Artropatias/fisiopatologia , Síndrome Metabólica , Doenças Musculoesqueléticas/etiologia , Doenças Musculoesqueléticas/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologia , Doenças Reumáticas , Adipocinas/metabolismo , Artrite , Humanos , Artropatias/metabolismo , Leptina/metabolismo , Doenças Musculoesqueléticas/metabolismo , Obesidade/metabolismo , Osteoartrite/etiologia , Osteoartrite/metabolismo , Osteoartrite/fisiopatologia , Doenças Reumáticas/etiologia , Doenças Reumáticas/metabolismo , Doenças Reumáticas/fisiopatologia
5.
Int J Mol Sci ; 20(19)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561459

RESUMO

Chemerin is widely recognized as an adipokine, with diverse biological roles in cellular differentiation and metabolism, as well as a leukocyte chemoattractant. Research investigating the role of chemerin in the obesity-cancer relationship has provided evidence both for pro- and anti-cancer effects. The tumor-promoting effects of chemerin primarily involve direct effects on migration, invasion, and metastasis as well as growth and proliferation of cancer cells. Chemerin can also promote tumor growth via the recruitment of tumor-supporting mesenchymal stromal cells and stimulation of angiogenesis pathways in endothelial cells. In contrast, the majority of evidence supports that the tumor-suppressing effects of chemerin are immune-mediated and result in a shift from immunosuppressive to immunogenic cell populations within the tumor microenvironment. Systemic chemerin and chemerin produced within the tumor microenvironment may contribute to these effects via signaling through CMKLR1 (chemerin1), GPR1 (chemerin2), and CCLR2 on target cells. As such, inhibition or activation of chemerin signaling could be beneficial as a therapeutic approach depending on the type of cancer. Additional studies are required to determine if obesity influences cancer initiation or progression through increased adipose tissue production of chemerin and/or altered chemerin processing that leads to changes in chemerin signaling in the tumor microenvironment.


Assuntos
Adipocinas/metabolismo , Quimiocinas/metabolismo , Neoplasias/etiologia , Neoplasias/metabolismo , Transdução de Sinais , Adipocinas/genética , Animais , Biomarcadores , Suscetibilidade a Doenças , Humanos , Imunomodulação , Neoplasias/patologia , Obesidade/complicações , Obesidade/metabolismo , Especificidade de Órgãos , Ligação Proteica
6.
BMC Pharmacol Toxicol ; 20(1): 58, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511067

RESUMO

BACKGROUND: Among adipose-derived factors, adipocytokines play roles as hormones and signaling mediators for apoptotic pathway. Among of them, vaspin, regulates the metabolism of adipose tissue itself as an endocrine organ, and stimulates adipocytes to maturation, differentiation, etc. Damaged adipocytes, present in obesity and hepatocellular carcinoma (HCC) respond with over-production of inflammatory cytokines. Such pro-inflammatory stimulation remains under adipokine control. Pro-inflammatory pathways are connected to oxidative stress and apoptosis, reported as co-existing with an elevated level of some adipokines in cancer cell lines. However, some hormones, such as vaspin, reduce apoptosis, have anti-inflammatory and anti-oxidative roles in cancer cell lines. METHODS: Hep-3B cells were cytometrically evaluated under vaspin treatment for reactive oxygen species (ROS) and apoptosiss induction. The statistical significant changes to the untreated controls was calculated by T-tests (indicated at value p < 0.05). RESULTS: Here we studied the production of reactive oxygen and nitrogen species in cells of HCC line Hep-3B after vaspin treatment. A decreased level of nitric oxide and superoxide anion 24 h after vaspin addition at 5 ng/ml was correlated with restricted, to the physiological level, apoptosis. A protective role of vaspin was displayed as enhanced cell viability and proliferation, which could be a poor prognostic in liver cancer. CONCLUSIONS: Apoptosis was suppressed after vaspin treatment, together with low levels of nitric oxide and superoxide anions.


Assuntos
Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Serpinas/uso terapêutico , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/metabolismo , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo
7.
BMC Vet Res ; 15(1): 324, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492181

RESUMO

BACKGROUND: Obesity in cats has been associated with alterations in adipokines including: adiponectin, interleukin-6 (IL6), and tumor necrosis factor-α (TNFα). Omega-3 polyunsaturated fatty acids have multiple beneficial effects on obesity-associated disorders, and therefore may alleviate these alterations. This study aimed to determine the effects of body condition, fat depot, troglitazone, and different fatty acids on secretion of adiponectin, IL6 and TNFα from adipose tissue of healthy cats. Subcutaneous and visceral adipose tissue samples were collected from 18 healthy intact female cats, and body condition score (Range 3-7/9) was determined. Concentrations of adiponectin were measured in mature adipocytes cultures and concentrations of IL6 and TNFα were measured in stromovascular cells cultures following treatment with control medium, troglitazone at 10 µM, eicosapentaenoic acid, arachidonic acid, or palmitic acid, at 25, 50, or 100 µM. RESULTS: Stromovascular cells of visceral origin secreted higher concentrations of IL6 than corresponding cells of subcutaneous origin (P = 0.003). Arachidonic acid treatment at 25, 50, and 100 µM increased IL6 secretion in subcutaneous (P = 0.045, P = 0.002, and P < 0.001, respectively) and visceral (P = 0.034, P = 0.001, and P < 0.001, respectively) stromovascular cells. Eicosapentaenoic acid treatment increased TNFα secretion in subcutaneous stromovascular cells at 25, 50, and 100 µM (P = 0.002, P = 0.001, and P = 0.015, respectively) and in visceral stromovascular cells at 50 µM (P < 0.001). No significant effect on medium adiponectin concentration was observed following troglitazone treatment (P = 0.4) or fatty acids treatments at 25 (P = 0.2), 50 (P = 0.8), or 100 (P = 0.7) µM. Body condition score did not have significant effects on medium concentrations of adiponectin (P = 0.4), IL6 (P = 0.1), or TNFα (P = 0.8). CONCLUSIONS: This study demonstrated higher basal secretion of IL6 from visceral compared to subcutaneous adipose tissue, a stimulatory effect of arachidonic acid on secretion of IL6 and a stimulatory effect of eicosapentaenoic acid on TNFα from feline adipose tissue.


Assuntos
Adipocinas/metabolismo , Tecido Adiposo/efeitos dos fármacos , Gorduras na Dieta/farmacologia , Ácidos Graxos/farmacologia , Tecido Adiposo/metabolismo , Animais , Ácido Araquidônico/metabolismo , Constituição Corporal , Gatos , Células Cultivadas , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/metabolismo , Feminino , Interleucina-6/metabolismo , Ácido Palmítico/metabolismo , Troglitazona/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
8.
Int J Mol Sci ; 20(16)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434216

RESUMO

Adipose tissue is a major endocrine organ capable of secreting adipokines with a role in whole-body metabolism. Changes in the secretome profile during the development of obesity is suspected to contribute to the risk of health complications such as those associated with weight regain after weight loss. However, the number of studies on weight regain is limited and secretome changes during weight regain have hardly been investigated. In an attempt to generate leads for in vivo studies, we have subjected human Simpson Golabi Behmel Syndrome adipocytes to glucose restriction (GR) followed by refeeding (RF) as an in vitro surrogate for weight regain after weight loss. Using LC-MS/MS, we compared the secreted protein profile after GR plus RF with that of normal feeding (NF) to assess the consequences of GR plus RF. We identified 338 secreted proteins of which 49 were described for the first time as being secreted by adipocytes. In addition, comparison between NF and GR plus RF showed 39 differentially secreted proteins. Functional classification revealed GR plus RF-induced changes of enzymes for extracellular matrix modification, complement system factors, cathepsins, and several proteins related to Alzheimer's disease. These observations can be used as clues to investigate metabolic consequences of weight regain, weight cycling or intermittent fasting.


Assuntos
Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Catepsinas/metabolismo , Glucose/farmacologia , Adipocinas/metabolismo , Células Cultivadas , Cromatografia Líquida , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Humanos , Espectrometria de Massas em Tandem
9.
Mol Cell Biochem ; 462(1-2): 107-114, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31463780

RESUMO

The aim of the work was to study the influence of vaspin on oxidative stress-induced apoptosis of mouse mesenchymal stem cells (MSCs). MSCs originated from bone marrow of C57BL/6 mouse were treated with vaspin and/or H2O2 in a dose-dependent manner. Cellular viability detected by CCK-8 and cell apoptosis studied by flow cytometry and TUNEL assay were observed in these cells. The protein expressions of PI3K, p-PI3K, Akt, p-Akt, T-ERK1/2, p-ERK1/2, p38, p-p38, JNK, and p-JNK were tested by Western blot. Vaspin had no significant effect on cellular viability, but significantly reduced H2O2-induced apoptosis. Western blot assay showed that pretreatment with vaspin promoted the activation of p-p38. Inhibition of p38 by SB203580 suppressed the protective effect of vaspin on oxidative stress-induced apoptosis. Vaspin inhibits oxidative stress-induced apoptosis of MSCs via the activation of MAPK/p38 signaling pathway. These findings indicate that vaspin is prone to osteoporosis protection.


Assuntos
Adipocinas/metabolismo , Apoptose , Citoproteção , Sistema de Sinalização das MAP Quinases , Células-Tronco Mesenquimais/enzimologia , Células-Tronco Mesenquimais/patologia , Estresse Oxidativo , Serpinas/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Adipocinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serpinas/farmacologia
10.
Int J Mol Sci ; 20(17)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443349

RESUMO

Rheumatic diseases encompass a diverse group of chronic disorders that commonly affect musculoskeletal structures. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common, leading to considerable functional limitations and irreversible disability when patients are unsuccessfully treated. Although the specific causes of many rheumatic conditions remain unknown, it is generally accepted that immune mechanisms and/or uncontrolled inflammatory responses are involved in their etiology and symptomatology. In this regard, the bidirectional communication between neuroendocrine and immune system has been demonstrated to provide a homeostatic network that is involved in several pathological conditions. Adipokines represent a wide variety of bioactive, immune and inflammatory mediators mainly released by adipocytes that act as signal molecules in the neuroendocrine-immune interactions. Adipokines can also be synthesized by synoviocytes, osteoclasts, osteoblasts, chondrocytes and inflammatory cells in the joint microenvironment, showing potent modulatory properties on different effector cells in OA and RA pathogenesis. Effects of adiponectin, leptin, resistin and visfatin on local and systemic inflammation are broadly described. However, more recently, other adipokines, such as progranulin, chemerin, lipocalin-2, vaspin, omentin-1 and nesfatin, have been recognized to display immunomodulatory actions in rheumatic diseases. This review highlights the latest relevant findings on the role of the adipokine network in the pathophysiology of OA and RA.


Assuntos
Adipocinas/metabolismo , Artrite Reumatoide/etiologia , Artrite Reumatoide/metabolismo , Adipocinas/genética , Animais , Artrite Reumatoide/patologia , Biomarcadores , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Humanos , Leptina/genética , Leptina/metabolismo , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Resistina/genética , Resistina/metabolismo , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
11.
Nat Rev Endocrinol ; 15(9): 507-524, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31296970

RESUMO

In addition to their role in glucose and lipid metabolism, adipocytes respond differentially to physiological cues or metabolic stress by releasing endocrine factors that regulate diverse processes, such as energy expenditure, appetite control, glucose homeostasis, insulin sensitivity, inflammation and tissue repair. Both energy-storing white adipocytes and thermogenic brown and beige adipocytes secrete hormones, which can be peptides (adipokines), lipids (lipokines) and exosomal microRNAs. Some of these factors have defined targets; for example, adiponectin and leptin signal through their respective receptors that are expressed in multiple organs. For other adipocyte hormones, receptors are more promiscuous or remain to be identified. Furthermore, many of these hormones are also produced by other organs and tissues, which makes defining the endocrine contribution of adipose tissues a challenge. In this Review, we discuss the functional role of adipose tissue-derived endocrine hormones for metabolic adaptations to the environment and we highlight how these factors contribute to the development of cardiometabolic diseases. We also cover how this knowledge can be translated into human therapies. In addition, we discuss recent findings that emphasize the endocrine role of white versus thermogenic adipocytes in conditions of health and disease.


Assuntos
Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Doenças do Sistema Endócrino/metabolismo , Nível de Saúde , Cardiopatias/metabolismo , Doenças Metabólicas/metabolismo , Animais , Doenças do Sistema Endócrino/fisiopatologia , Cardiopatias/fisiopatologia , Hormônios/metabolismo , Humanos , Doenças Metabólicas/fisiopatologia
12.
Endocrinology ; 160(10): 2367-2387, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265057

RESUMO

Prolonged exposure to glucocorticoids (GCs) causes various metabolic derangements. These include obesity and insulin resistance, as inhibiting glucose utilization in adipose tissues is a major function of GCs. Although adipose tissue distribution and glucose homeostasis are sex-dependently regulated, it has not been evaluated whether GCs affect glucose metabolism and adipose tissue functions in a sex-dependent manner. In this study, high-dose corticosterone (rodent GC) treatment in C57BL/6J mice resulted in nonfasting hyperglycemia in male mice only, whereas both sexes displayed hyperinsulinemia with normal fasting glucose levels, indicative of insulin resistance. Metabolic testing using stable isotope-labeled glucose techniques revealed a sex-specific corticosterone-driven glucose intolerance. Corticosterone treatment increased adipose tissue mass in both sexes, which was reflected by elevated serum leptin levels. However, female mice showed more metabolically protective adaptations of adipose tissues than did male mice, demonstrated by higher serum total and high-molecular-weight adiponectin levels, more hyperplastic morphological changes, and a stronger increase in mRNA expression of adipogenic differentiation markers. Subsequently, in vitro studies in 3T3-L1 (white) and T37i (brown) adipocytes suggest that the increased leptin and adiponectin levels were mainly driven by the elevated insulin levels. In summary, this study demonstrates that GC-induced insulin resistance is more severe in male mice than in female mice, which can be partially explained by a sex-dependent adaptation of adipose tissues.


Assuntos
Glicemia/metabolismo , Corticosterona/toxicidade , Resistência à Insulina , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adipocinas/genética , Adipocinas/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Tecido Adiposo/efeitos dos fármacos , Animais , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Homeostase/efeitos dos fármacos , Insulina/farmacologia , Leptina/genética , Leptina/metabolismo , Masculino , Camundongos , Fatores Sexuais
13.
Physiol Rev ; 99(4): 1701-1763, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31339053

RESUMO

Obesity is increasingly prevalent and is associated with substantial cardiovascular risk. Adipose tissue distribution and morphology play a key role in determining the degree of adverse effects, and a key factor in the disease process appears to be the inflammatory cell population in adipose tissue. Healthy adipose tissue secretes a number of vasoactive adipokines and anti-inflammatory cytokines, and changes to this secretory profile will contribute to pathogenesis in obesity. In this review, we discuss the links between adipokine dysregulation and the development of hypertension and diabetes and explore the potential for manipulating adipose tissue morphology and its immune cell population to improve cardiovascular health in obesity.


Assuntos
Tecido Adiposo/fisiopatologia , Pressão Sanguínea , Diabetes Mellitus/fisiopatologia , Hipertensão/fisiopatologia , Obesidade/fisiopatologia , Adipocinas/metabolismo , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Adiposidade , Animais , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/imunologia , Diabetes Mellitus/metabolismo , Humanos , Hipertensão/epidemiologia , Hipertensão/imunologia , Hipertensão/metabolismo , Mediadores da Inflamação/metabolismo , Obesidade/epidemiologia , Obesidade/imunologia , Obesidade/metabolismo , Fenótipo , Medição de Risco , Fatores de Risco , Transdução de Sinais , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia
14.
Int Rev Immunol ; 38(4): 157-171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31286783

RESUMO

Obesity predisposes the affected individuals to several metabolic, inflammatory, cardiovascular and malignant pathologies and is a top risk factor for premature mortality. It is now well known that inflammation has a major causative role in obesity-associated disease development and that obesity favors the establishment of a pro-inflammatory milieu at the level of adipose microenvironment. These inflammatory signals result in a disruption of normal cellular-crosstalk between adipose and non-adipose components leading to an altered metabolic and immunological status and a dysfunctional phenotype. Abnormal secretion of adipokines - small adipose-derived signaling molecules - can further assist in the inflammatory processes to offset the adipose tissue towards a dysfunctional state. Although adipokines have been recognized as the link between obesity and pathogenesis, studies are needed to fully understand their mechanism of action and underscore their therapeutic value. Here, we have reviewed obesity-induced metabolic and immunological changes at the level of vasculature and emphasize on the importance of adipokines, particularly leptin, vaspin and visfatin, for their therapeutic relevance.


Assuntos
Adipocinas/metabolismo , Células Endoteliais/imunologia , Mediadores da Inflamação/metabolismo , Obesidade/imunologia , Tecido Adiposo/imunologia , Tecido Adiposo/patologia , Células Endoteliais/patologia , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Obesidade/metabolismo , Transdução de Sinais
15.
PLoS One ; 14(6): e0218543, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31220177

RESUMO

Spirulina platensis is a blue-green algae with potential anti-obesity effects. In this study, the anti-obesity effects of whole Spirulina platensis (WSP), Spirulina platensis protein (SPP) and Spirulina platensis protein hydrolysate (SPPH) were compared in high-fat diet fed mice, and the potential acting mechanism of SPPH was also investigated. Totally, SPPH exhibited good anti-obesity effects (reducing 39.8%±9.7% of body weight), lowering 23.8%±1.6% of serum glucose, decreasing 20.8%±1.4% of total cholesterol, while positive drug Simvastatin had the corresponding values: 8.3%±4.6%, 24.8%±1.9% and -2.1%±0.2%, respectively. Subsequently, PCR array was used to conduct gene expression analysis in brain and liver tissues of SPPH-treated mice, which displayed distinctly different expression pattern. The most markedly changed genes included: Acadm (-34.7 fold), Gcg (2.5 fold), Adra2b (2 fold) and Ghsr (2 fold) in brain; Retn (39 fold), Fabp4 (15.5 fold), Ppard (6 fold) and Slc27a1 (5.4 fold) in liver. Further network analysis demonstrated that the significantly expressed genes in brain and liver tissues were mapped into an interacting network, suggesting a modulatory effect on brain-liver axis, major pathways were involved in the axis: PPAR, adipocytokine, AMPK, non-alcoholic fatty liver disease and MAPK. This study showed that Spirulina platensis protein hydrolysate possessed anti-obesity effect in mice.


Assuntos
Fármacos Antiobesidade/farmacologia , Encéfalo/efeitos dos fármacos , Fígado/efeitos dos fármacos , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Hidrolisados de Proteína/farmacologia , Spirulina/química , Adipocinas/genética , Adipocinas/metabolismo , Animais , Fármacos Antiobesidade/uso terapêutico , Encéfalo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/prevenção & controle , Receptores Ativados por Proliferador de Peroxissomo/genética , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Extratos Vegetais/uso terapêutico , Hidrolisados de Proteína/uso terapêutico , Proteínas Quinases/genética , Proteínas Quinases/metabolismo
16.
Life Sci ; 231: 116580, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31216440

RESUMO

AIMS: Chemerin has been recently identified as a vasoactive adipokine implicated in blood pressure regulation. In this context, we evaluated whether chemerin could influence pulmonary vasoreactive response. MATERIALS AND METHODS: Vascular reactivity to chemerin and to phenylephrine, serotonin and endothelin-1 after chemerin pretreatment was evaluated in rat isolated pulmonary artery versus thoracic aorta with and without endothelium. Vasoreactivity to acetylcholine in presence of nitric oxide (NO)-synthase inhibitor (L-NAME) and to NO donor sodium nitroprusside (SNP) was evaluated in chemerin-pretreated pulmonary artery versus thoracic aorta with endothelium. Pretreatment with ODQ, a soluble guanylate cyclase inhibitor and apocynin, a ROS production inhibitor, were also tested. Arteries and lung tissue were harvested for pathobiological evaluation. KEY FINDINGS: Chemerin contracted endothelium-denuded pulmonary artery, while no response was observed in arteries with endothelium. Chemerin potentiated phenylephrine-, endothelin-1- and serotonin-induced vasoconstriction, which was further enhanced by endothelium removal. Chemerin decreased acetylcholine-induced vasorelaxation in arteries with endothelium, while it did not affect SNP-induced relaxation. In presence of L-NAME, there remained a vasorelaxation in chemerin-pretreated arteries. Chemerin or ODQ alone partly decreased acetylcholine-induced vasorelaxation in pulmonary artery and thoracic aorta, while combined chemerin and ODQ incubation abolished it. Treatment with apocynin partly or totally reversed chemerin effects. In both types of arteries, chemerin reduced acetylcholine-induced NO production, as well as endothelial and inducible NO-synthase expression. SIGNIFICANCE: Chemerin potentiates vascular responses to vasoconstrictors in pulmonary artery and thoracic aorta and, impairs acetylcholine-induced pulmonary artery vasodilatation, by mechanisms involving at least partly NO signaling and oxidative stress.


Assuntos
Quimiocinas/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Artéria Pulmonar/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Acetilcolina/farmacologia , Adipocinas/metabolismo , Animais , Quimiocinas/metabolismo , Endotelina-1/metabolismo , Endotelinas/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Nitroprussiato/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fenilefrina/farmacologia , Artéria Pulmonar/metabolismo , Ratos , Ratos Wistar , Serotonina/metabolismo , Artérias Torácicas/efeitos dos fármacos , Artérias Torácicas/metabolismo , Vasoconstritores/farmacologia , Vasodilatação/efeitos dos fármacos
17.
Cells ; 8(6)2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234447

RESUMO

Though historically regarded as an inert energy store, adipose tissue is a complex endocrine organ, which is increasingly implicated in the pathogenesis of inflammatory bowel disease (IBD). Accumulating evidence points to visceral adipose tissue and specifically to its mesenteric component, or "creeping fat" as impacting on the disease course through its immunomodulatory properties. On the one hand, mesenteric fat acts as a physical barrier to inflammation and is involved in controlling host immune response to translocation of gut bacteria. On the other hand, however, there exists a strong link between visceral fat and complicated course of the disease with unfavorable therapeutic outcomes. Furthermore, "creeping fat" appears to play different roles in different IBD phenotypes, with the greatest pathogenetic contribution probably to an ileal form of Crohn's disease. In this review, we summarize and discuss the existing literature on the subject and identify high-priority areas for future research. It may be that a better understanding of the role of mesenteric fat in IBD will determine new therapeutic targets and translate into improved clinical outcomes.


Assuntos
Tecido Adiposo/patologia , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/terapia , Adipocinas/metabolismo , Animais , Progressão da Doença , Humanos , Fenótipo , Resultado do Tratamento
18.
Eur Respir Rev ; 28(152)2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31243096

RESUMO

Obstructive sleep apnoea (OSA) is a major health concern worldwide and adversely affects multiple organs and systems. OSA is associated with obesity in >60% of cases and is independently linked with the development of numerous comorbidities including hypertension, arrhythmia, stroke, coronary heart disease and metabolic dysfunction. The complex interaction between these conditions has a significant impact on patient care and mortality. The pathophysiology of cardiometabolic complications in OSA is still incompletely understood; however, the particular form of intermittent hypoxia (IH) observed in OSA, with repetitive short cycles of desaturation and re-oxygenation, probably plays a pivotal role. There is fast growing evidence that IH mediates some of its detrimental effects through adipose tissue inflammation and dysfunction. This article aims to summarise the effects of IH on adipose tissue in experimental models in a comprehensive way. Data from well-designed controlled trials are also reported with the final goal of proposing new avenues for improving phenotyping and personalised care in OSA.


Assuntos
Tecido Adiposo/fisiopatologia , Adiposidade , Apneia Obstrutiva do Sono/fisiopatologia , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Animais , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Pressão Positiva Contínua nas Vias Aéreas , Metabolismo Energético , Humanos , Mediadores da Inflamação/metabolismo , Pulmão/metabolismo , Pulmão/fisiopatologia , Transdução de Sinais , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/terapia , Resultado do Tratamento
19.
Biosci Biotechnol Biochem ; 83(11): 2000-2007, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31250712

RESUMO

In this study, we examined the mechanism of Flavone of Hippophae (H-flavone) in regulating macrophage foaming and atherosclerosis (AS) plaque formation. H-flavone treatment increased the secretion of C1q/tumor necrosis factor-related proteins 6 (CTRP6) in Ox-LDL-treated mouse peripheral blood macrophage cells (PBMC) and significantly reduced the percentage of cholesteryl ester (CE) in PBMC. Additionally, H-flavone suppressed Ox-LDL-induced cell foaming and the production of inflammatory cytokines through upregulating CTPR6 expression. Next, we further validated the inhibitory effect of H-flavone on plaque formation and inflammation in a mouse AS model. A substantial reduction in the secretion of inflammatory cytokines was observed in apoE-/- mice by H-flavone. Immunohistochemistry and Oil Red O staining results showed that H-flavone suppressed macrophage infiltration and the development of AS plaque. These effects were more pronounced in early administration. Our results suggest that H-flavone effectively inhibits macrophage foaming, inflammation and vascular plaque formation by upregulating CTRP6 and may be used to reduce AS risk.


Assuntos
Adipocinas/metabolismo , Aterosclerose/prevenção & controle , Flavonas/farmacologia , Flores/química , Hippophae/química , Macrófagos/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Animais , Aterosclerose/sangue , Aterosclerose/metabolismo , LDL-Colesterol/sangue , Citocinas/biossíntese , Metabolismo dos Lipídeos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Fatores de Risco , Triglicerídeos/sangue
20.
Int J Mol Sci ; 20(11)2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31195622

RESUMO

Diabetes is a contributor to morbidity across the globe and is often associated with obesity, metabolic syndrome and other inflammatory diseases associated with aging. In addition to genetic and lifestyle factors, environmental factors such as metals and persistent organic pollutants may increase the severity or lower the threshold of these conditions. In cell culture, methylmercury is toxic to adipocytes and may impact adipokine secretions. In this study, we determined the effects of different concentrations of theaflavin digallate on methylmercury exposed 3T3-L1 adipocytes in cell culture. Secretions of resistin, adiponectin and lipid peroxidation product, 4-hydroxynonenal (4-HNE) were monitored using ELISA assays. Cell morphology of methylmercury and theaflavin-3,3'-digallate treated adipocytes was assessed using Lipid (Oil Red O) staining. Exposure to methylmercury increased the levels of resistin and adiponectin as well as 4-HNE when compared to the control cells. Methylmercury treated cells resulted in smaller number of adipocytes and clumped lipid droplets. These results suggest that methylmercury induces reactive oxygen species leading to development of an inflammatory response. Theaflavin-3,3'-digallate reduced the impact of methylmercury by maintaining the adipocytes morphology and secretion patterns of adiponectin, resistin and 4-hydroxynonenal. With this experimental model system other anti-inflammatory and signaling agents could be tested at the biochemical level before eventually leading to studies in animal models.


Assuntos
Adipócitos/citologia , Adipocinas/metabolismo , Biflavonoides/farmacologia , Catequina/farmacologia , Diferenciação Celular , Ácido Gálico/análogos & derivados , Compostos de Metilmercúrio/toxicidade , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adiponectina/metabolismo , Aldeídos/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Ácido Gálico/farmacologia , Camundongos , Resistina/metabolismo
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