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1.
Medicine (Baltimore) ; 99(8): e19120, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080087

RESUMO

Osteoporosis (OP) is a disease characterized by bone mass loss, bone microstructure damage, increased bone fragility, and easy fracture. The molecular mechanism underlying OP remains unclear.In this study, we identified 217 genes associated with OP, and formed a gene set [OP-related genes gene set (OPgset)].The highly enriched GOs and pathways showed OPgset genes were significantly involved in multiple biological processes (skeletal system development, ossification, and osteoblast differentiation), and several OP-related pathways (Wnt signaling pathway, osteoclast differentiation, steroid hormone biosynthesis, and adipocytokine signaling pathway). Besides, pathway crosstalk analysis indicated three major modules, with first module consisted of pathways mainly involved in bone development-related signaling pathways, second module in Wnt-related signaling pathway and third module in metabolic pathways. Further, we calculated degree centrality of a node and selected ten key genes/proteins, including TGFB1, IL6, WNT3A, TNF, PTH, TP53, WNT1, IGF1, IL10, and SERPINE1. We analyze the K-core and construct three k-core sub-networks of OPgset genes.In summary, we for the first time explored the molecular mechanism underlying OP via network- and pathway-based methods, results from our study will improve our understanding of the pathogenesis of OP. In addition, these methods performed in this study can be used to explore pathogenesis and genes related to a specific disease.


Assuntos
Osso e Ossos/patologia , Fraturas Ósseas/etiologia , Osteoporose/genética , Adipocinas/genética , Densidade Óssea/genética , Osso e Ossos/metabolismo , Osso e Ossos/ultraestrutura , Diferenciação Celular/genética , Biologia Computacional/métodos , Regulação da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Humanos , Osteoblastos/fisiologia , Osteoclastos/fisiologia , Osteogênese/genética , Osteoporose/complicações , Osteoporose/epidemiologia , Prevalência , Via de Sinalização Wnt/genética
2.
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
3.
Gene ; 721: 144113, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31505214

RESUMO

Vaspin, initially identified in visceral adipose tissue, is an adipokine, and administration of recombinant vaspin leads to lowering of the endoplasmic reticulum stress which is elevated in obesity or enhancement of insulin sensitivity. CCAAT/enhancer binding protein (C/EBP), as a basic leucine zipper transcription factor, plays a critical role in adipocyte development and glucose and lipid metabolisms in liver. The present study aimed to investigate the effect of C/EBPα on vaspin gene expression. The expression of hepatic vaspin was markedly decreased in liver-specific C/EBPα knockout mice. A reporter assay indicated that two C/EBP-responsive elements (CEBPREs) are necessary for C/EBPα-dependent induction of vaspin promoter activities. Furthermore, electrophoretic mobility shift assay showed that C/EBPα in mouse liver is capable of directly binding the two CEBPREs. These results suggest that C/EBPα positively regulates hepatic vaspin expression through two functional CEBPREs. Thus, vaspin is a novel C/EBPα target gene in the liver.


Assuntos
Adipocinas/biossíntese , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Regulação da Expressão Gênica/fisiologia , Fígado/metabolismo , Elementos de Resposta/fisiologia , Serpinas/biossíntese , Adipocinas/genética , Animais , Camundongos , Camundongos Knockout , Serpinas/genética
4.
Diabetes Metab Syndr ; 13(4): 2593-2599, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31405681

RESUMO

Obesity is a well-known chronic low-grade inflammation condition characterized by dysregulated adipokine secretion and function. Both CTRP12 and CTRP13 are adipokines that influence glucose and lipid metabolism. We aimed to investigate CTRP12, CTRP13, and inflammatory gene expressions in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from obese women who underwent bariatric surgery in comparison with the normal weight women. This case-control study included 20 obese [body mass index (BMI) > 35-40 kg/m2] candidates for bariatric surgery and 20 normal-weight women (BMI <25 kg/m2) as control group, who underwent elective surgeries. Real-time PCR was used to evaluate mRNA expression levels of CTRP12, CTRP13, and inflammatory genes in SAT and VAT from both groups. We observed significantly higher mRNA expression of CTRP12 in SAT (p = 0.048) and VAT (p = 0.046) from obese patients compared to the controls. There was significantly greater expression of IL-6 and MCP-1 inflammatory genes in SAT (p = 0.013 and p = 0.005 respectively) and VAT (p = 0.000 and p = 0.001 respectively) of obese patients compared to the control group. IL-1ß (p = 0.015) and TNF-α (p = 0.014) expressions significantly increased in VAT from obese patients compared to the control group. Spearman correlation analysis showed that CTRP12 expression significantly correlated with obesity indices. Our findings showed that CTRP12 significantly increased in both VAT and SAT of obese group. More importantly, we observed a positive correlation between CTRP12 with inflammatory parameters. These results indicated that CTRP12 might be part of an intricate network for glucose metabolism and obesity-related inflammation processes.


Assuntos
Adipocinas/genética , Biomarcadores/análise , Complemento C1q/genética , Regulação da Expressão Gênica , Gordura Intra-Abdominal/metabolismo , Obesidade/genética , Gordura Subcutânea/metabolismo , Adolescente , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Resistência à Insulina , Gordura Intra-Abdominal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/patologia , Prognóstico , Gordura Subcutânea/fisiopatologia , Regulação para Cima , Adulto Jovem
5.
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
6.
Int J Mol Sci ; 20(15)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382403

RESUMO

Adipokines are a potential link between reproduction and energy metabolism and could partly explain some infertilities related to some pathophysiology, such as polycystic ovary syndrome (PCOS). However, adipokines were predominantly assessed in blood samples, while very little is known concerning their variations in follicular fluid (FF) and ovarian granulosa cells (GCs) of PCOS women. Thus, the objectives of our study were to investigate adiponectin, chemerin, resistin, visfatin, omentin, and apelin ovarian expression in PCOS women in comparison with controls and women with only a polycystic ovary morphology. In total, 78 women undergoing an in vitro fertilization procedure were divided into three groups: 23 PCOS women, 28 women presenting only ≥12 follicles per ovary (ECHO group), and 27 control women. Each group almost equally included normal weight and obese women. Follicular fluid (FF) concentration and granulosa cells (GCs) mRNA expression of adipokines and their receptors were assessed by ELISA and RT-qPCR, respectively. Omentin levels in FF and GC were higher in PCOS than in ECHO and control women, while apelin expression was increased in both PCOS and ECHO groups. FF chemerin concentration was predominant in normal-weight PCOS women compared to BMI (Body Mass Index)-matched ECHO and control women, while GC mRNA levels were higher in the obese PCOS group than in the ECHO one. Compared to PCOS, ECHO women had increased FF adiponectin concentrations and lower plasma AMH levels. The FF concentration of all adipokines was higher in obese subjects except for adiponectin, predominant in normal-weight women. In conclusion, women with PCOS expressed higher GC chemerin and omentin, whereas the ECHO group presented higher levels of FF adiponectin and apelin and lower plasma AMH and LH concentrations. Chemerin, omentin, and apelin expression was differently regulated in women with PCOS, suggesting their possible role in follicular growth arrest and ovulatory dysfunction characterizing PCOS pathogenesis.


Assuntos
Adipocinas/genética , Apelina/genética , Quimiocinas/genética , Citocinas/genética , Lectinas/genética , Síndrome do Ovário Policístico/genética , Feminino , Proteínas Ligadas por GPI/genética , Regulação da Expressão Gênica , Humanos , Ovário/metabolismo , Ovário/patologia , Ovulação , Síndrome do Ovário Policístico/patologia , Síndrome do Ovário Policístico/fisiopatologia
7.
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
8.
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
9.
Braz Oral Res ; 33: e034, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31038568

RESUMO

Specific variants in genes that encode adipokines and their mRNA and protein expression were previously studied in type 2 diabetes mellitus (T2DM) and obesity, and similar studies have been performed for chronic periodontitis (CP). The aim of this case-control study was to investigate the possible impacts of adiponectin (ADIPOQ), leptin (LEP) and its receptor (LEPR), and resistin (RETN) on the etiopathogenesis of CP. Examinations were performed on 118 non-periodontitis healthy subjects (healthy controls, HC), 205 healthy individuals with CP (H + CP) and 86 type 2 diabetes patients with CP (T2DM + CP). Variants within the ADIPOQ (rs2241766, rs1501299), LEP (rs13228377, rs2167270), LEP receptor (rs1805096), and RETN (rs1862513) genes were determined by qPCR. In addition, the plasma levels of ADIPOQ, LEP, and RETN were analysed by ELISA for 80 individuals. The genotype frequencies of the SNP ADIPOQ +45G/T (rs2241766) differed between the HC and H + CP groups (p=0.03, pcorr>0.05), and carriers of the TT genotype had a lower risk of developing CP compared to carriers of the GG or TG genotypes (p<0.01, pcorr>0.05). However, there were no significant differences in the plasma levels of ADIPOQ, LEP or RETN between the study groups (p > 0.05). Plasma levels of the adipokines were also independent of the gene profiles (p > 0.05). Adipokine plasma levels did not change in patients with H + CP/T2DM + CP compared to HC, but we did identify a specific polymorphism in the ADIPOQ gene that was associated with CP. Although the ADIPOQ +45G/T (rs2241766) gene variant may be a candidate biomarker for CP, further research is required in larger populations with different ethnic backgrounds before any final conclusions can be drawn about the role of this gene in CP.


Assuntos
Adipocinas/sangue , Adipocinas/genética , Periodontite Crônica/sangue , Diabetes Mellitus Tipo 2/sangue , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Análise de Variância , Biomarcadores/sangue , Estudos de Casos e Controles , Periodontite Crônica/genética , Diabetes Mellitus Tipo 2/genética , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estatísticas não Paramétricas
10.
Genes (Basel) ; 10(5)2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083422

RESUMO

Obesity is associated with white adipose tissue (WAT) hypoxia and inflammation. We aimed to test whether mild environmental oxygen restriction (OxR, 13% O2), imposing tissue hypoxia, triggers WAT inflammation in obese mice. Thirteen weeks diet-induced obese male adult C57BL/6JOlaHsd mice housed at thermoneutrality were exposed for five days to OxR versus normoxia. WAT and blood were isolated and used for analysis of metabolites and adipokines, WAT histology and macrophage staining, and WAT transcriptomics. OxR increased circulating levels of haemoglobin and haematocrit as well as hypoxia responsive transcripts in WAT and decreased blood glucose, indicating systemic and tissue hypoxia. WAT aconitase activity was inhibited. Macrophage infiltration as marker for WAT inflammation tended to be decreased, which was supported by down regulation of inflammatory genes S100a8, Ccl8, Clec9a, Saa3, Mgst2, and Saa1. Other down regulated processes include cytoskeleton remodelling and metabolism, while response to hypoxia appeared most prominently up regulated. The adipokines coiled-coil domain containing 3 (CCDC3) and adiponectin, as well as the putative WAT hormone cholecystokinin (CCK), were reduced by OxR on transcript (Cck, Ccdc3) and/or serum protein level (adiponectin, CCDC3). Conclusively, our data demonstrate that also in obese mice OxR does not trigger WAT inflammation. However, OxR does evoke a metabolic response in WAT, with CCDC3 and adiponectin as potential markers for systemic or WAT hypoxia.


Assuntos
Tecido Adiposo Branco/metabolismo , Hipóxia/genética , Obesidade/genética , Adipocinas/genética , Adipocinas/metabolismo , Tecido Adiposo Branco/patologia , Animais , Biomarcadores/metabolismo , Dieta Hiperlipídica , Regulação da Expressão Gênica , Hipóxia/metabolismo , Inflamação/genética , Inflamação/metabolismo , Ácido Láctico/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Temperatura Ambiente
11.
Int J Mol Sci ; 20(10)2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31137678

RESUMO

Adipocyte and hepatic lipid metabolism govern whole-body metabolic homeostasis, whereas a disbalance of de novo lipogenesis (DNL) in fat and liver might lead to obesity, with severe co-morbidities. Nevertheless, some obese people are metabolically healthy, but the "protective" mechanisms are not yet known in detail. Especially, the adipocyte-derived molecular mediators that indicate adipose functionality are poorly understood. We studied transgenic mice (alb-SREBP-1c) with a "healthy" obese phenotype, and obob mice with hyperphagia-induced "sick" obesity to analyze the impact of the tissue-specific DNL on the secreted proteins, i.e., the adipokinome, of the primary adipose cells by label-free proteomics. Compared to the control mice, adipose DNL is reduced in both obese mouse models. In contrast, the hepatic DNL is reduced in obob but elevated in alb-SREBP-1c mice. To investigate the relationship between lipid metabolism and adipokinomes, we formulated the "liver-to-adipose-tissue DNL" ratio. Knowledge-based analyses of these results revealed adipocyte functionality with proteins, which was involved in tissue remodeling or metabolism in the alb-SREBP-1c mice and in the control mice, but mainly in fibrosis in the obob mice. The adipokinome in "healthy" obesity is similar to that in a normal condition, but it differs from that in "sick" obesity, whereas the serum lipid patterns reflect the "liver-to-adipose-tissue DNL" ratio and are associated with the adipokinome signature.


Assuntos
Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Ácidos Graxos não Esterificados/sangue , Obesidade/metabolismo , Adipocinas/genética , Animais , Lipogênese , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
12.
Am J Clin Nutr ; 109(6): 1499-1510, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30869115

RESUMO

BACKGROUND: The adipose tissue (AT) is a secretory organ producing a wide variety of factors that participate in the genesis of metabolic disorders linked to excess fat mass. Weight loss improves obesity-related disorders. OBJECTIVES: Transcriptomic studies on human AT, and a combination of analyses of transcriptome and proteome profiling of conditioned media from adipocytes and stromal cells isolated from human AT, have led to the identification of apolipoprotein M (apoM) as a putative adipokine. We aimed to validate apoM as novel adipokine, investigate the relation of AT APOM expression with metabolic syndrome and insulin sensitivity, and study the regulation of its expression in AT and secretion during calorie restriction-induced weight loss. METHODS: We examined APOM mRNA level and secretion in AT from 485 individuals enrolled in 5 independent clinical trials, and in vitro in human multipotent adipose-derived stem cell adipocytes. APOM expression and secretion were measured during dieting. RESULTS: APOM was expressed in human subcutaneous and visceral AT, mainly by adipocytes. ApoM was released into circulation from AT, and plasma apoM concentrations correlate with AT APOM mRNA levels. In AT, APOM expression inversely correlated with adipocyte size, was lower in obese compared to lean individuals, and reduced in subjects with metabolic syndrome and type 2 diabetes. Regardless of fat depot, there was a positive relation between AT APOM expression and systemic insulin sensitivity, independently of fat mass and plasma HDL cholesterol. In human multipotent adipose-derived stem cell adipocytes, APOM expression was enhanced by insulin-sensitizing peroxisome proliferator-activated receptor agonists and inhibited by tumor necrosis factor α, a cytokine that causes insulin resistance. In obese individuals, calorie restriction increased AT APOM expression and secretion. CONCLUSIONS: ApoM is a novel adipokine, the expression of which is a hallmark of healthy AT and is upregulated by calorie restriction. AT apoM deserves further investigation as a potential biomarker of risk for diabetes and cardiovascular diseases.


Assuntos
Adipocinas/genética , Apolipoproteínas M/genética , Obesidade/dietoterapia , Obesidade/genética , Adipócitos/metabolismo , Adipocinas/metabolismo , Apolipoproteínas M/metabolismo , Restrição Calórica , Ensaios Clínicos como Assunto , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo
13.
Int J Neurosci ; 129(10): 978-985, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30885017

RESUMO

Aim: The association between adiponectin, leptin, and resistin and the long-term outcome of ischemic stroke are controversial. We aimed to evaluate this relationship. Methods: We prospectively studied 83 patients consecutively hospitalized for acute ischemic stroke (38.6% males, age 79.7 ± 6.3 years). Serum adiponectin, leptin, and resistin levels and the -420C > G polymorphism of the resistin gene were determined at admission. Stroke severity at admission was evaluated with the National Institutes of Health Stroke Scale (NIHSS). One year after discharge, functional status, incidence of cardiovascular events and all-cause mortality were recorded. Functional status was evaluated with the modified Rankin scale (mRS). Results: Patients with the G allele had lower mRS (p < .05) and patients with adverse outcome had higher serum resistin levels (p < .05). The only independent predictor of adverse outcome was mRS at discharge (risk ratio (RR) 2.78, 95% confidence interval (CI) 1.54-5.00; p < .001). Higher adiponectin levels were an independent predictor of cardiovascular morbidity (RR 1.07, 95% CI 1.01-1.14; p < .05). Patients who died had higher serum adiponectin levels than those who survived (p < .05). The only independent predictor of all-cause mortality was NIHSS at admission (RR 1.19, 95% CI 1.04-1.35; p < .01). Conclusions: In patients with acute ischemic stroke, the G allele of the -420C > G polymorphism of the resistin gene promoter is more frequent in those with a more favorable functional outcome at one year after discharge. Patients with higher serum resistin levels appear to have worse long-term functional outcome, while higher serum adiponectin levels are associated with higher incidence of cardiovascular events.


Assuntos
Adipocinas/genética , Isquemia Encefálica/genética , Polimorfismo Genético/genética , Resistina/genética , Acidente Vascular Cerebral/genética , Adipocinas/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Isquemia Encefálica/sangue , Feminino , Hospitalização/tendências , Humanos , Masculino , Estudos Prospectivos , Resistina/sangue , Acidente Vascular Cerebral/sangue , Fatores de Tempo , Resultado do Tratamento
14.
Iran J Allergy Asthma Immunol ; 18(1): 62-71, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30848574

RESUMO

Obese asthma is a new asthma phenotype. The underlying mechanisms are not clearly understood. Leptin and adiponectin are two predominant adipokines produced by adipose tissue. Studies have demonstrated a role of leptin on regulating the Janus kinase/signal transducer and ativator of transcription protein (JAK/STAT) signaling pathway and STAT3, STAT6 were known to have essential role on inflammatory cytokines production. However, whether STAT3 and STAT6 are activated and related to leptin merit further investigation. The aim of this study was to investigate the expression levels of leptin/adiponectin ratio and the activations of STAT3 and STAT6 in the lungs of obese asthma mice. Experiments were carried out on male C57/B6J mice. The proteins in bronchoalveolar lavage fluid (BALF) were measured using ELISA. The expression levels of the transcriptional and translational factors in the lungs were examined using Quantitative Reverse Transcriptase Polymerase Chain reaction (qRT-PCR) and western blot. The expression levels of leptin in the BALF of normal weight group, asthma group, obese group and obese asthma group were 2.032±0.133, 5.375±0.123, 5.418±0.165 and 7.486±0.168, respectively. The expression of leptin in obese asthma group was the highest (p<0.05) ,while the expression of adiponectin the lowest (p<0.05). The expression level of P-STAT3 in the obese asthma group was 0.9244±0.014, and was significantly higher than three other groups (p<0.05). The expressions of P-STAT6 in three other groups were all significantly higher than normal weight group (p<0.05). Our data suggest that the function of leptin on the pulmonary inflammation of obese asthma may be partly through activating the STAT3 signaling pathway.


Assuntos
Adipocinas/metabolismo , Asma/metabolismo , Obesidade/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT6/metabolismo , Adipocinas/genética , Animais , Asma/patologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Modelos Animais de Doenças , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Obesidade/patologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT6/genética
15.
Biochem Biophys Res Commun ; 510(3): 388-394, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30717975

RESUMO

The browning of white adipose tissue predominantly emerges as an adaptation to environmental cues, such as cold exposure. The enhanced browning of adipose tissue results in improved energy and glucose homeostasis and reduced fat mass and body weight, which is greatly beneficial for the treatment of obesity and other metabolic diseases. C1q/TNF-related protein 5 (CTRP5) is a novel adipokine associated with a variety of endocrine and metabolic diseases; however, whether it can regulate the metabolism of adipose tissue itself remains unknown. In this study, we demonstrated that the expression of CTRP5 in murine subcutaneous white adipose tissue (scWAT) was significantly decreased when the mice were exposed to cold temperatures. The lentivirus-mediated overexpression of CTRP5 in mice repressed the adipose tissue browning, leading to reduced heat production, decreased expression of the browning marker uncoupling protein 1 (UCP1) and decreased browning-related gene expression. Mechanistically, we found that autophagy was inhibited after cold exposure, but this inhibition was alleviated after CTRP5 overexpression. In primary cultured adipocytes, CTRP5 suppressed UCP1 expression, whereas 3-MA (an autophagy inhibitor) rescued the suppression. All of these results demonstrated that CTRP5 is a negative regulator of adipose browning. CTRP5 exerts its effect, at least in part, by suppressing adipocyte autophagy. Our findings indicated that CTRP5 is a novel promising therapeutic target for obesity and other metabolic diseases.


Assuntos
Adipocinas/metabolismo , Tecido Adiposo Branco/metabolismo , Temperatura Baixa , Proteínas de Membrana/metabolismo , Adipócitos/fisiologia , Adipocinas/genética , Tecido Adiposo Branco/fisiologia , Animais , Autofagia , Células Cultivadas , Metabolismo Energético , Regulação da Expressão Gênica , Masculino , Proteínas de Membrana/genética , Camundongos Endogâmicos C57BL
16.
Theriogenology ; 127: 56-65, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30665074

RESUMO

C1q/tumor necrosis factor-related protein 6 (CTRP6) is a newly identified adiponectin paralog with modulating effects on metabolism and inflammation. CTRP6 transcript is detected in human ovarian tissue. However, the expression pattern and function of CTRP6 on ovary have been rarely studied. In the present study, we preliminarily examined the structure feature and function of CTRP6 in porcine granulosa cells. The results indicated that the signaling peptide of CTRP6 was located at among positions 21 and 22, and the phosphorylation sites were at 15 (Ser), 4 (Thr) and 4 (Tyr), respectively. Meanwhile, CTRP6 was extremely homologous in livestock and chiropteran. The qPCR results showed that CTRP6 was moderately expressed in porcine follicle. Immunohistochemistry manifested that CTRP6 was presented in various types of ovarian cells. Immunofluorescence revealed that CTRP6 was located in cytoplasm in primary porcine granulosa cells. ELISA results showed that the concentration of CTRP6 in the follicular fluid was gradually decreased with the growth of antral follicle. In addition FSH increased CTRP6 expression levels in a time- and dose-dependent manner in primary porcine granulosa cells, while LH had no effect on CTRP6 basal gene expression, which suggesting CTRP6 is an FSH-responsive gene in porcine granulosa cells. Our findings imply that the CTRP6 may be a candidate gene to regulate folliculogenesis and reproductive performance.


Assuntos
Adipocinas/metabolismo , Hormônio Foliculoestimulante/fisiologia , Células da Granulosa/metabolismo , Ovário/metabolismo , Suínos , Adipocinas/análise , Adipocinas/genética , Sequência de Aminoácidos , Animais , Citoplasma/metabolismo , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Hormônio Foliculoestimulante/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Imuno-Histoquímica/veterinária , Fosforilação , Alinhamento de Sequência , Análise de Sequência de Proteína
17.
J Anim Sci ; 97(1): 220-230, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30321363

RESUMO

The impact of body condition in late gestating gilts on gene expression of selected adipokines and their receptors in backfat and mammary fat tissues was studied. The presence of associations between mammary gland composition variables and the mRNA abundance of selected genes and serum concentrations of adiponectin and leptin was also investigated. A total of 45 gilts were selected at mating based on their backfat depth and were allocated to three groups: (1) low backfat (LBF; 12-15 mm; n = 14), (2) medium backfat (MBF; 17-19 mm; n = 15), and (3) high backfat (HBF; 22-26 mm; n = 16). Gilts were fed different amounts of a conventional diet to maintain differences in backfat depth throughout the gestation period. Blood samples were collected at day 109 of gestation to measure adiponectin and leptin serum concentrations. Gilts were slaughtered on day 110 of gestation, and mammary glands were collected to determine mammary composition. Mammary fat and backfat tissues were also sampled to measure the mRNA abundance of selected genes. In mammary fat tissue, there was an effect of body condition on the prolactin (PRL; P = 0.01), adiponutrin (PNPLA3; P < 0.10), and prolactin receptor long form (PRLR-LF; P < 0.10) genes. There was a greater PRL mRNA abundance in mammary fat tissue from HBF than LBF or MBF gilts (P < 0.05). The PNPLA3 mRNA abundance was lower in HBF than in MBF gilts (P < 0.05), and that of PRLR-LF was lower in LBF than in HBF gilts (P < 0.05). In backfat, body condition affected the mRNA abundance of leptin (P < 0.05) and PNPLA3 (P < 0.01), with the greatest expression levels being observed in HBF gilts for both genes. Association analyses suggest a detrimental effect of high circulating leptin concentrations on gilts mammary development, as reflected by the negative correlations between serum leptin and protein percent (r = -0.66, P < 0.01), and concentrations of DNA (r = -0.62, P < 0.01) and RNA (r = -0.60, P < 0.01) in mammary parenchyma. Current results show that body condition of gilts at the end of gestation can affect the expression of adipokines in mammary fat and backfat tissues, with a different regulation of transcript abundance being observed in these two fat depots. Results also suggest that circulating leptin is strongly associated with mammary gland composition of late pregnant gilts, whereas locally synthesized leptin from mammary fat tissue is not.


Assuntos
Adipocinas/genética , Proteínas de Membrana/sangue , Receptores da Prolactina/genética , Suínos/fisiologia , Adipocinas/sangue , Adiponectina/sangue , Adiponectina/genética , Tecido Adiposo/fisiologia , Animais , Composição Corporal , Dieta/veterinária , Feminino , Leptina/sangue , Leptina/genética , Glândulas Mamárias Animais/fisiologia , Proteínas de Membrana/genética , Gravidez , Prolactina/sangue , Prolactina/genética , RNA Mensageiro/genética , Receptores da Prolactina/sangue , Suínos/sangue , Suínos/genética
18.
Sci Rep ; 8(1): 17518, 2018 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-30504920

RESUMO

Psychiatric disorders have been widely reported to be associated with systemic inflammation upregulation and adiposity. However, there are no data that link adipose tissue inflammation to these mental disorders. The analysis of adipokines and inflammation-related markers in adipose tissue could help to elucidate the potential association between obesity and mental health. An observational study was conducted in samples of patients consisting of non-obese and obese subjects, who were diagnosed with anxiety or mood disorders. Gene expression of adiponectin (ADIPOQ), leptin (LEP) and inflammatory markers (IL6, IL1B, TNF, CCL2, CSF3, ITGAM, and PLAUR) were determined in visceral (VAT) and subcutaneous (SAT) adipose tissues. Our results showed that the gene expression of adipokines and inflammation-related markers was higher in the VAT and SAT of obese subjects compared with non-obese subjects. Regarding mental disorders, all the inflammatory genes in the VAT were significantly higher in non-obese subjects with anxiety or mood disorders than in subjects without mental disorders, except for TNF and ITGAM. Additionally, IL6 expression was significantly lower in SAT. In contrast, obese patients diagnosed with anxiety or mood disorders only showed significantly lower expression levels of IL1B in VAT and ADIPOQ in SAT when compared with obese subjects without mental disorders. These data suggest the potential involvement of VAT inflammation in anxiety and mood disorders, involving complex mechanisms which are strongly affected by obesity.


Assuntos
Tecido Adiposo/metabolismo , Transtornos de Ansiedade/diagnóstico , Perfilação da Expressão Gênica , Mediadores da Inflamação/metabolismo , Inflamação/genética , Transtornos do Humor/diagnóstico , Obesidade/complicações , Adipocinas/genética , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/genética , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/complicações , Transtornos do Humor/genética , Obesidade/genética
19.
BMB Rep ; 51(12): 611-612, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30463644

RESUMO

C1q/TNF-α-Related Protein 1 (CTRP1) has recently been shown to act as a blood pressure regulator, as it induces vasoconstriction. In the aorta, CTRP1 facilitates recruitment of angiotensin II receptor 1 (AT1R) to plasma membrane, through activation of the AKT/AS160 signaling pathway. This leads to activation of the Ras homolog gene family (Rho)/Rho kinase (ROCK) signaling pathway, resulting in vasoconstriction. Accordingly, mice overexpressing Ctrp1 have hypertensive phenotype. Patients with hypertension also display higher circulating CTRP1 levels, compared to healthy individuals, indicating that excessive CTRP1 may affect development of hypertension. Conversely, CTRP1 is regarded as an 'innate blood pressure modulator' because CTRP1 increases blood pressure under dehydration to prevent hypotension. Mice lacking Ctrp1 fail to maintain normotension under dehydration conditions, resulting in hypotension, suggesting that CTRP1 is an essential protein for maintaining blood pressure homeostasis. In conclusion, CTRP1 is a novel, anti-hypotensive vasoconstrictor that increases blood pressure during dehydrationinduced hypotension. [BMB Reports 2018; 51(12): 611-612].


Assuntos
Adipocinas/metabolismo , Pressão Sanguínea/fisiologia , Adipocinas/sangue , Adipocinas/genética , Animais , Desidratação , Glucocorticoides/farmacologia , Hipertensão/metabolismo , Hipertensão/patologia , Camundongos , Camundongos Knockout , Músculo Esquelético/metabolismo , Transdução de Sinais , Regulação para Cima/efeitos dos fármacos , Quinases Associadas a rho/metabolismo
20.
Adv Biol Regul ; 70: 19-30, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30473005

RESUMO

Adipose tissue lies at the heart of obesity, mediating its many effects upon the rest of the body, with its unique capacity to expand and regenerate, throughout the lifespan of the organism. Adipose is appreciated as an endocrine organ, with its myriad adipokines that elicit both physiological and pathological outcomes. Sphingolipids, bioactive signaling molecules, affect many aspects of obesity and the metabolic syndrome. While sphingolipids are appreciated in the context of these diseases in other tissues, there are many discoveries yet to be uncovered in the adipose tissue. This review focuses on the effects of sphingolipids on various aspects of adipose function and dysfunction. The processes of adipogenesis, metabolism and thermogenesis, in addition to inflammation and insulin resistance are intimately linked to sphingolipids as discussed below.


Assuntos
Tecido Adiposo/metabolismo , Obesidade/metabolismo , Esfingolipídeos/metabolismo , Adipocinas/genética , Adipocinas/metabolismo , Animais , Humanos , Obesidade/genética
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