Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 472
Filtrar
1.
Medicine (Baltimore) ; 99(5): e18924, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000405

RESUMO

Adiponectin is an adipose tissue-derived cytokine that exerts its antiinflammatory effects by binding to 2 adiponectin receptors, adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2). However, the role of these adiponectin receptors on inflammatory pain remains unclear. We investigated the association between single nucleotide polymorphisms (SNPs) of these genes and inflammatory pain, such as postoperative pain and cancer pain.We analyzed 17 SNPs of the ADIPOR1 gene and 27 SNPs of the ADIPOR2 gene in 56 adult patients with postlaparotomy pain. We compared these genotypes with pain intensity and opioid consumption, adjusting for multiple testing. We analyzed the genotypes of 88 patients with cancer pain and examined the association of the relevant SNP(s) with pain intensity and opioid consumption.One variant of the ADIPOR1 gene (rs12045862) showed significant association with postoperative pain intensity; patients with minor allele homozygote (n = 7) demonstrated significantly worse pain intensity than that of combined patient group exhibiting major allele homozygote or the heterozygote (n = 49; Mann-Whitney test, P < .00002), although their opioid consumptions were comparable. Cancer pain intensity between minor allele homozygote patients (n = 7) and other 2 genotype patients (n = 81) were comparable.The rs12045862 SNP of the ADIPOR1 gene was associated with postoperative pain but not cancer pain. This might result from functional alteration of the ADIPOR1 signalling pathways, which influence the inflammatory process. ADIPOR1 may be a novel potential target for developing analgesics of postoperative pain.


Assuntos
Dor do Câncer/genética , Dor Pós-Operatória/genética , Polimorfismo de Nucleotídeo Único , Receptores de Adiponectina/genética , Analgésicos Opioides/uso terapêutico , Dor do Câncer/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Feminino , Estudos de Associação Genética , Humanos , Inflamação/genética , Laparotomia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico
2.
Anim Reprod Sci ; 208: 106110, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31405469

RESUMO

Adiponectin is an adipocyte derived cytokine implicated in energy homeostasis, insulin resistance and is involved in the regulation of reproduction both centrally and peripherally in animals. The present study was conducted to investigate adiponectin (ADIPOQ) and its receptors ADIPOR1 and ADIPOR2 abundance of mRNA transcript and protein in different stages of corpora lutea (CL) development during the estrous cycle of water buffalo and to determine the effect of adiponectin on cultured luteal cells of water buffalo (Bubalus bubalis). The results indicate adiponectin, ADIPOR1, and ADIPOR2 were present in buffalo corpora lutea (CL) throughout the estrous cycle. The abundance of adiponectin and its receptors was greater in the early and regressing and was less in mid- and late-stages of CL functionality. Adiponectin and its receptors were localized in the cytoplasm of small and large luteal cells. Furthermore, luteal cells were cultured in the in-vitro culture system and were treated with 1 and 10 µg/mL dose of adiponectin for 48 h. Adiponectin at both doses decreased (P < 0.05) progesterone (P4) secretion from cultured luteal cells and also suppressed the abundance of factors involved in P4productionv [Steroidogenic Acute Regulatory Protein (STAR), cytochrome P45011A1 (CYP11A1) and 3ß-hydroxysteroid dehydrogenase (HSD3B1) at the 10 µg/mL dose as compared to adiponectin non-supplemented cells]. In conclusion, results of the present study indicate adiponectin and its receptors are present in bubaline CL and adiponectin inhibits P4 production in cultured luteal cells. The findings indicate adiponectin affects luteal dynamics and reproductive functions in water buffalo.


Assuntos
Adiponectina/metabolismo , Búfalos/fisiologia , Corpo Lúteo/metabolismo , Ciclo Estral/fisiologia , Regulação da Expressão Gênica/fisiologia , RNA Mensageiro/metabolismo , Adiponectina/genética , Animais , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Feminino , Imuno-Histoquímica , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/metabolismo , Progesterona/metabolismo , Progesterona Redutase/genética , Progesterona Redutase/metabolismo , RNA Mensageiro/genética , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Esteroide Isomerases/genética , Esteroide Isomerases/metabolismo
3.
Reprod Domest Anim ; 54(9): 1291-1303, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31339602

RESUMO

Adiponectin is an adipocyte-derived hormone regulating energy metabolism, insulin sensitivity and recently found to regulate reproduction. The current study was carried out to investigate gene and protein expression, immunolocalization of adiponectin and its receptors AdipoR1 and AdipoR2 in ovarian follicles of different developmental stages in water buffalo (Bubalus bubalis) and to investigate the effect of adiponectin on steroid production in cultured bubaline granulosa cells. qPCR, western blotting and immunohistochemistry were applied to demonstrate mRNA expression, protein expression and immunolocalization, respectively. The results indicate that adiponectin, AdipoR1 and AdipoR2 were present in granulosa cells (GC) and theca interna (TI) of ovarian follicles and the expression of adiponectin, AdipoR1, AdipoR2 in GC and AdipoR1 and AdipoR2 in TI increased with increase in follicle size (p < .05). Expression of adiponectin was high in small and medium size follicles in TI. The adiponectin and its receptors were immunolocalized in the cytoplasm of GC and TI cells. Further, in the in-vitro study, GCs were cultured and treated with recombinant adiponectin each at 0, 1 and 10 µg/ml alone or with follicle stimulating hormone (FSH) at 30 ng/ml) or Insulin-like growth factor I (IGF-I) at 10 ng/ml for 48 hr after obtaining 75%-80%s confluency. Adiponectin at 10 µg/ml increased IGF-I-induced estradiol (E2 ) and progesterone (P4 ) secretion and FSH-induced E2 secretion from GC and also increased the abundance of factors involved in E2 and P4 production (cytochrome P45019A1 [CYP19A1] and 3-beta-hydroxysteroid dehydrogenase [3ß-HSD]). In conclusion, this study provides novel evidence for the presence of adiponectin and its receptors in ovarian follicles and modulatory role of adiponectin on steroid production in buffalo.


Assuntos
Adiponectina/fisiologia , Búfalos/metabolismo , Receptores de Adiponectina/fisiologia , Adiponectina/genética , Adiponectina/farmacologia , Animais , Células Cultivadas , Estradiol/metabolismo , Feminino , Hormônio Foliculoestimulante/farmacologia , Regulação da Expressão Gênica , Células da Granulosa/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Folículo Ovariano/metabolismo , Progesterona/metabolismo , Receptores de Adiponectina/genética , Células Tecais/metabolismo
4.
Int J Mol Sci ; 20(12)2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31212761

RESUMO

Adipose tissue has been recognized as a complex organ with endocrine and metabolic roles. The excess of fat mass, as occurs during overweight and obesity states, alters the regulation of adipose tissue, contributing to the development of obesity-related disorders. In this regard, many epidemiological studies shown an association between obesity and numerous types of malignancies, comprising those linked to the endocrine system (e.g., breast, endometrial, ovarian, thyroid and prostate cancers). Multiple factors may contribute to this phenomenon, such as hyperinsulinemia, dyslipidemia, oxidative stress, inflammation, abnormal adipokines secretion and metabolism. Among adipokines, growing interest has been placed in recent years on adiponectin (APN) and on its role in carcinogenesis. APN is secreted by adipose tissue and exerts both anti-inflammatory and anti-proliferative actions. It has been demonstrated that APN is drastically decreased in obese individuals and that it can play a crucial role in tumor growth. Although literature data on the impact of APN on carcinogenesis are sometimes conflicting, the most accredited hypothesis is that it has a protective action, preventing cancer development and progression. The aim of the present review is to summarize the currently available evidence on the involvement of APN and its signaling in the etiology of cancer, focusing on endocrine malignancies.


Assuntos
Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Neoplasias das Glândulas Endócrinas/etiologia , Obesidade/complicações , Obesidade/metabolismo , Adiponectina/química , Adiponectina/genética , Animais , Biomarcadores , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Neoplasias das Glândulas Endócrinas/diagnóstico , Neoplasias das Glândulas Endócrinas/metabolismo , Neoplasias das Glândulas Endócrinas/terapia , Humanos , Insulina/metabolismo , Modelos Biológicos , Metástase Neoplásica , Comunicação Parácrina , Ligação Proteica , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Risco , Medição de Risco , Relação Estrutura-Atividade
5.
Int J Med Sci ; 16(4): 519-528, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31171903

RESUMO

Oesophageal adenocarcinoma (OAC) is an exemplar model of obesity-associated cancer. Response to neoadjuvant chemoradiotherapy (NA CRT) is a clinical challenge. We examined if visceral adipose tissue and obesity status alter radiosensitivity in OAC. The radioresistant (OE33R) and radioresponsive (OE33P) OAC isogenic model was cultured with adipose tissue conditioned media from three patient cohorts: non-cancer patients, surgery only OAC patients and NA CRT OAC patients. Cell survival was characterised by clonogenic assay, metabolomic profiling by nuclear magnetic resonance spectroscopy and adipokine receptor gene expression by qPCR. A retrospective in vivo study compared tumour response to NA CRT in normal weight (n=53) versus overweight/obese patients (n=148). Adipose conditioned media (ACM) from all patient cohorts significantly increased radiosensitivity in radioresistant OE33R cells. ACM from the NA CRT OAC cohort increased radiosensitivity in OE33P cells. Metabolomic profiling demonstrated separation of the non-cancer and surgery only OAC cohorts and between the non-cancer and NA CRT OAC cohorts. Gene expression profiling of OE33P versus OE33R cells demonstrated differential expression of the adiponectin receptor-1 (AR1), adiponectin receptor-2 (AR2), leptin receptor (LepR) and neuropilin receptor-1 (NRP1) genes. In vivo overweight/obese OAC patients achieved an enhanced tumour response following NA CRT compared to normal weight patients. This study demonstrates that visceral adipose tissue modulates the cellular response to radiation in OAC.


Assuntos
Adenocarcinoma/radioterapia , Neoplasias Esofágicas/radioterapia , Gordura Intra-Abdominal/efeitos dos fármacos , Obesidade Abdominal/radioterapia , Tolerância a Radiação/efeitos dos fármacos , Adenocarcinoma/genética , Adenocarcinoma/patologia , Índice de Massa Corporal , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Gordura Intra-Abdominal/patologia , Masculino , Metabolômica , Obesidade Abdominal/genética , Obesidade Abdominal/patologia , Receptores de Adiponectina/genética , Receptores para Leptina/efeitos da radiação
6.
Food Funct ; 10(6): 3334-3343, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31095141

RESUMO

This study was conducted to investigate the effect and underlying mechanism of Resveratrol (RES) in regulating skeletal muscle fiber-type switching. We found that RES had no effect on the body weight and food intake of Kunming mice (KM mice) that were orally administered with 400 mg kg-1 d-1 RES for 12 weeks. Notably, the RES administration significantly increased the expression of myosin heavy chain (MyHC) 1, MyHC2a, and MyHC2x in the extensor digitorum longus (EDL) and soleus (SOL) muscles. Furthermore, the muscle immunostaining of the results showed that the RES treatment led to the myofiber type transition from glycolytic to oxidative in muscles. The mRNA and protein levels of the adiponectin receptor (AdipoR), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in EDL and SOL were drastically increased after RES treatment. Moreover, the plasma Adiponectin (AdipoQ) protein levels were higher in the RES-treated mice compared to the control mice. Moreover, the in vitro results further demonstrated that the 20 µM RES treatment increased the expression of AdipoR1, AdipoR2, AMPK, PGC-1α and MyHC1, but decreased the expression of MyHC2b in C2C12 myoblasts. Furthermore, mechanistic studies revealed that silencing the AdiopR1, not the AdiopR2, abolished the effect of RES on the expression of AMPK and PGC-1α in the C2C12 cells. These results indicated that RES could regulate skeletal fiber switching through the AdiopR1-AMPK-PGC-1α pathway. This work may provide a new strategy for enhancing endurance and relieving muscle diseases caused by oxidative muscle fiber deficiency.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Receptores de Adiponectina/metabolismo , Resveratrol/administração & dosagem , Proteínas Quinases Ativadas por AMP/genética , Adiponectina/sangue , Animais , Masculino , Camundongos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/enzimologia , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Receptores de Adiponectina/genética , Transdução de Sinais/efeitos dos fármacos
7.
Gene ; 702: 148-152, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30940525

RESUMO

Obesity increases the risk of developing hypertension. Since both pathological entities constitute public health problems, the aim of this study was to investigate RNA expression of adiponectin, leptin and their receptors in adipose tissue in women with class 3 obesity, with or without hypertension. Serum concentrations of these adipokines were also quantitated. Women with obesity and hypertension (n = 22) and with obesity without hypertension (n = 37) were included. All patients presented class 3 obesity, without diabetes mellitus. The expression of mRNA in: adiponectin, ADIPOR1 and ADIPOR2 was analyzed in visceral (VAT) and subcutaneous (SAT) adipose tissue; leptin and its receptor were only analyzed in SAT, by reverse transcription quantitative PCR. Measurements of adiponectin and leptin concentrations were performed using enzyme-linked immunosorbent assay kits. Analysis of mRNA expressions in VAT and SAT are presented as median and quartiles. Analysis of serum concentrations of adipokines are presented as median and percentiles 25th-75th. Women presenting a higher mean arterial pressure, had significantly higher levels of mRNA expression of adiponectin in SAT. Besides, we found several significant positive correlations of these adipokines and their receptors. In conclusion, we found that those women with a higher mean arterial pressure and receiving antihypertensive treatment, presented higher levels of mRNA expression of adiponectin in SAT.


Assuntos
Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Hipertensão/complicações , Obesidade/metabolismo , Adiponectina/sangue , Adiponectina/genética , Adulto , Feminino , Humanos , Gordura Intra-Abdominal/metabolismo , Leptina/sangue , Obesidade/sangue , Obesidade/complicações , RNA Mensageiro/metabolismo , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Gordura Subcutânea/metabolismo
8.
Eur J Pharmacol ; 853: 289-298, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30978318

RESUMO

C1q/TNF-related protein-9(CTRP9) is an adipose cytokine, a closest adiponectin paralog, which has anti-inflammatory, antioxidant, vasodilation and anti-atherosclerosis effects. In addition, it can increase insulin sensitivity, decrease blood glucose level and inhibit the apoptosis of endothelial cells. However, it remains unclear whether CTRP9 has beneficial effects on diabetic retinopathy (DR). An adenoviral vector expressing CTRP9 was intravenously injected into db/db mice, aged 12 weeks, at day 15 post injection, and the process was repeated. The transfection efficiency of CTRP9 was assessed by enzyme linked immunosorbent assay. We used RT-PCR, immunofluorescence, and Western blot to determine proinflammatory cytokines, adhesion molecules and tight-junction proteins. The breakdown of blood-retinal barrier (BRB) was evaluated using Evans blue and retinal staining. CTRP9 suppresses the expression of interleukin-1 beta, tumor necrosis factor-alpha, monocyte chemotactic protein-1 and adhesion molecules in the retina of db/db mice. CTRP9 can balance the expression of pigment epithelium-derived factor and vascular endothelial growth factor. CTRP9 can also inhibit the activation of nuclear factor Kappa B in the retina of db/db mouse. In addition, CTRP9 can prevent the breakdown of BRB and downregulation of tight-junction proteins in the retina of db/db mice. Evans blue assay revealed the breakdown of BRB and vascular leakage in the retinas of diabetic mice. CTRP9 can both qualitatively and quantitatively alleviate the vascular leakage in the early stage of diabetic retinas. CTRP9 can inhibit the inflammation of diabetic retinopathy and protect blood-retinal barrier via decreasing proinflammatory cytokines and preventing the downregulation of tight-junction proteins.


Assuntos
Adiponectina/metabolismo , Glicoproteínas/metabolismo , Retina/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Inflamação/sangue , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores de Adiponectina/genética , Transcrição Genética/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
J Agric Food Chem ; 67(11): 3188-3197, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30827101

RESUMO

(-)-Hydroxycitric acid (HCA) inhibits the deposition of fat in animals and humans, while the molecular mechanism is still unclear. The present study investigated the effect and mechanism of (-)-HCA's regulation of lipid, glucose, and energy metabolism in broiler chickens. The current results showed that (-)-HCA decreased the accumulation of lipid droplets and triglyceride content by reducing fatty acid synthase protein level and enhancing phosphorylation of acetyl-CoA carboxylase protein level. (-)-HCA accelerated carbohydrate aerobic metabolisms by increasing the activities of phosphofructokinase-1, pyruvate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase. Furthermore, (-)-HCA increased adiponectin receptor 1 mRNA level and enhanced phospho-AMPKα, peroxisome proliferator-activated receptor gamma coactivator-1α, nuclear respiratory factor-1, and mitochondrial transcription factor A protein levels in broiler chickens. These data indicated that (-)-HCA reduced lipid droplet accumulation, improved glucose catabolism, and accelerated energy metabolism in broiler chickens, possibly via activation of adiponectin-AMPK signaling pathway. These results revealed the biochemical mechanism of (-)-HCA-mediated fat accumulation and the prevention of metabolic disorder-related diseases in broiler chickens.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/metabolismo , Galinhas/metabolismo , Citratos/metabolismo , Metabolismo Energético/efeitos dos fármacos , Garcinia cambogia/química , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Extratos Vegetais/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Adiponectina/genética , Ração Animal/análise , Animais , Galinhas/genética , Garcinia cambogia/metabolismo , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triglicerídeos/metabolismo
10.
Domest Anim Endocrinol ; 68: 54-63, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30851697

RESUMO

Here we characterized gene expressions in subcutaneous adipose tissue and blood metabolites of pigs with genetically low backfat (Landrace) and high backfat (Meishan). As pigs aged from 1 wk-to 3-mo old, mRNA levels of adipose-specific genes increased, although their gene expressions coding for major enzymes involved in lipid metabolism (lipoprotein lipase, fatty acid synthase, and hormone-sensitive lipase) did not differ between lean and fat pigs. Instead, there were significant effects for adiponectin and its receptor AdipoR1 mRNA levels between the two breeds of which respective expressions were lower and higher in Meishan by 3 mo of age. Contrary to changes in gene expressions, the concentrations of blood glucose, triglyceride (TG), and NEFA in both breeds decreased during growth, and 3-mo-old Meishan evidenced lower glucose with higher TG than the Landrace. The homeostasis model assessment insulin resistance (HOMA-IR) index was also calculated from the measurements of fasting glucose and insulin concentration, and Meishan showed a higher value than the Landrace. We next examined these differences in Landrace and Meishan crossbreds, which were phenotypically distinguishable by the backfat thickness as the former lean type and the latter fat type. As with the purebreds, high backfat Meishan crosses showed the characteristics of lower glucose and higher TG in circulating levels and also lower adiponectin transcripts in subcutaneous adipose tissue. Collectively, our results demonstrate that levels of adiponectin and its receptor gene expressions, blood glucose, blood lipids, and HOMA-IR in pigs vary between lean and fat. These observations strongly suggest the possibility that overall metabolic differences rather than adipocyte ability itself contribute to the fatness of genetically high backfat pigs.


Assuntos
Adiponectina/metabolismo , Tecido Adiposo/fisiologia , Composição Corporal/genética , Regulação da Expressão Gênica/fisiologia , Receptores de Adiponectina/metabolismo , Suínos/genética , Adiponectina/genética , Animais , Glicemia , Composição Corporal/fisiologia , Cruzamentos Genéticos , Feminino , Insulina/sangue , Insulina/metabolismo , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Adiponectina/genética , Suínos/fisiologia
11.
Clin Epigenetics ; 11(1): 20, 2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30732639

RESUMO

BACKGROUND: It is well established that obesity is associated with dysregulation of the ratio between the two major adipokines leptin and adiponectin. Furthermore, it was recently reported that maternal obesity has a significant impact on placental development. Leptin and adiponectin are present at the fetal-maternal interface and are involved in the development of a functional placenta. However, less is known about leptin and adiponectin's involvement in the placental alterations described in obese women. Hence, the objective of the present study was to characterize the placental expression and DNA methylation of these two adipokine systems (ligands and receptors) in obese women. RESULTS: Biopsies were collected from the fetal and maternal sides of third-trimester placenta in obese and non-obese (control) women. In both groups, leptin levels were higher on the fetal side than the maternal side, suggesting that this cytokine has a pivotal role in fetal growth. Secondly, maternal obesity (in the absence of gestational diabetes) was associated with (i) elevated DNA methylation of the leptin promoter on fetal side only, (ii) hypomethylation of the adiponectin promoter on the maternal side only, (iii) significantly low levels of leptin receptor protein (albeit in the absence of differences in mRNA levels and promoter DNA methylation), (iv) significantly low levels of adiponectin receptor 1 mRNA expression on the maternal side only, and (v) elevated DNA methylation of the adiponectin receptor 2 promoter on the maternal side only. CONCLUSION: Our present results showed that maternal obesity is associated with the downregulation of both leptin/adiponectin systems in term placenta, and thus a loss of the beneficial effects of these two adipokines on placental development. Maternal obesity was also associated with epigenetic changes in leptin and adiponectin systems; this highlighted the molecular mechanisms involved in the placenta's adaptation to a harmful maternal environment.


Assuntos
Adiponectina/genética , Metilação de DNA , Leptina/genética , Obesidade/complicações , Placenta/química , Receptores de Adiponectina/genética , Receptores para Leptina/genética , Adulto , Estudos de Casos e Controles , Regulação para Baixo , Epigênese Genética , Feminino , Humanos , Masculino , Idade Materna , Obesidade/genética , Gravidez , Terceiro Trimestre da Gravidez/genética , Regiões Promotoras Genéticas
12.
Int J Biol Sci ; 15(2): 253-264, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30745818

RESUMO

Adipokines are emerging as a link between obesity and obesity-related cancers, including pancreatic cancer. Adiponectin is an abundant adipokine with pleiotropic beneficial roles in metabolic disorders. Low adiponectin levels are commonly observed in human obesity and have been associated with increased pancreatic cancer risk in prospective epidemiologic studies. Here, we investigated the direct effect of adiponectin on human pancreatic cancer in vitro and in vivo. Our results showed that adiponectin treatment significantly inhibited the proliferation of human pancreatic cancer cells. Knockdown of adiponectin receptors completely eliminated the antiproliferation effect of adiponectin and markedly promoted the growth of human pancreatic cancer xenografts in nude mice. Further analysis revealed that adiponectin blocked the phosphorylation/inactivation of GSK-3ß, suppressed the intracellular accumulation of ß-catenin, reduced the expression of cyclin D1, and consequently caused cell cycle accumulation at the G0-G1 phase in pancreatic cancer cells. Adiponectin-mediated attenuation of cell proliferation was abrogated by the GSK-3ß inhibitor. In addition, a microarray analysis revealed that adiponectin also downregulated the expression of TCF7L2, a coactivator of ß-catenin, at the transcriptional level in pancreatic cancer cells. These results indicated that the protective role of adiponectin against human pancreatic cancer might be attributed to its attenuating effect on the ß-catenin signaling pathway. Taken together, our findings support a causal link between hypoadiponectinemia and increased pancreatic cancer risk, and suggest that activating adiponectin signaling could be a novel therapeutic strategy for obesity-related pancreatic cancer.


Assuntos
Adiponectina/farmacologia , Neoplasias Pancreáticas/metabolismo , Receptores de Adiponectina/metabolismo , beta Catenina/metabolismo , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Biologia Computacional , Ciclina D1/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Nus , Neoplasias Pancreáticas/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Adiponectina/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Int J Mol Med ; 43(3): 1542-1552, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30664190

RESUMO

Adiponectin (APN) exerts anti­inflammatory effects in various cells. Uric acid (UA) induces inflammation in proximal renal tubular epithelial cells (PTECs). It remains unknown whether APN protects against UA­induced inflammation. In the present study, human PTECs were incubated with 100 µg/ml soluble (S) UA in the presence or absence of globular (g) APN, APN receptor 1 (AdipoR1)­short hairpin RNA lentivirus or compound C. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) assays were performed to assess APN mRNA expression. Immunoblotting was used to assess the protein expression of APN, AdipoR1, NACHT, leucine rich repeat and pyrin domain­containing protein 3 (NLRP3) and the activation of tumor necrosis factor (TNF) α and adenosine monophosphate­activated protein kinase (AMPK). ELISA analyses were performed to assess supernatant levels of interleukin (IL)­1ß and TNFα. It was observed that SUA significantly enhanced APN mRNA and protein expression (both P<0.05) and increased NLRP3 (P<0.001) and TNFα (P<0.05) protein levels, as well as supernatant levels of IL­1ß (P<0.01) and TNFα (P<0.001) compared with untreated cells. gAPN administration significantly limited TNFα synthesis and secretion (both P<0.001), significantly decreased IL­1ß release (P<0.01), impacted NLRP3 protein expression and augmented AdipoR1 protein (P<0.01) and AMPK phosphorylation (P<0.05) levels compared with SUA­treated cells. AdipoR1 knockdown significantly promoted the synthesis (P<0.05) and release of TNFα (P<0.001), significantly increased IL­1ß supernatant levels (P<0.01) and exhibited little influence on NLRP3 production (P>0.05) compared with the SUA­treated cells. Secreted TNFα levels were significantly increased upon the inhibition of AMPK (P<0.05) and protein levels of IL­1ß, NLRP3 and TNFα in cell lysates were not significantly affected (P>0.05). In summary, the data demonstrated that SUA promoted APN expression in PTECs and that gAPN attenuated SUA­induced inflammation through the AdipoR1/AMPK signaling pathway. AdipoR1 knockdown and AMPK inactivation increased SUA­induced inflammatory damage in PTECs. These findings may help to further understand and regulate UA­associated inflammation in proximal renal tubules.


Assuntos
Adiponectina/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Substâncias Protetoras/farmacologia , Ácido Úrico/efeitos adversos , Biomarcadores , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Células Epiteliais/patologia , Técnicas de Silenciamento de Genes , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/etiologia , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Humanos , Mediadores da Inflamação/metabolismo , Túbulos Renais/patologia , Sistema de Sinalização das MAP Quinases , Modelos Biológicos , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo
14.
J Atheroscler Thromb ; 26(4): 328-339, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30135333

RESUMO

AIM: Adiponectin exhibits its biological effects through adiponectin receptors (AdipoR1 and AdipoR2), which are distributed in the kidneys, and activation of those receptors could prevent or ameliorate diabetic nephropathy. This study aimed to evaluate the associations between AdipoR single nucleotide polymorphisms (SNPs) and kidney function in an elderly Japanese population. METHODS: A total of 271 elderly Japanese volunteers underwent anthropometric and laboratory tests (cystatin C-based eGFR and total and high molecular weight adiponectin levels at baseline and a follow-up visit). Genotype data were obtained for the selected 7 and 5 AdipoR1 and AdipoR2 SNPs, respectively. RESULTS: In a cross-sectional analysis at baseline, we found a significant association between the AdipoR2 SNP rs12230440 and kidney function; eGFRcys tended to increase as the number of carriers of T alleles increased after adjustment for covariates and Bonferroni correction, although the association of the SNP and annual eGFR decline could not be identified in the longitudinal data. Regarding the variants rs16850797, rs11061925, and rs10773983, each of the allele G, allele C, and allele G showed nominally significant associations with higher eGFRcys. However, this failed to reach significance after Bonferroni correction. CONCLUSION: Here, an AdipoR2 SNP was associated with kidney function, suggesting that the effects of this polymorphism on adiponectin receptor may affect kidney function in the elderly Japanese population.


Assuntos
Biomarcadores/análise , Taxa de Filtração Glomerular , Nefropatias/genética , Rim/fisiopatologia , Polimorfismo de Nucleotídeo Único , Receptores de Adiponectina/genética , Idoso , Estudos Transversais , Feminino , Seguimentos , Genótipo , Humanos , Japão/epidemiologia , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Nefropatias/fisiopatologia , Testes de Função Renal , Estudos Longitudinais , Masculino , Prognóstico , Estudos Prospectivos
15.
J Agric Food Chem ; 67(1): 90-101, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30541285

RESUMO

Yellow-soybean-leaf extract includes kaempferol glycosides and pheophorbides that reduce obesity and plasma glucose levels. This study researched the molecular mechanisms underlying the glucose-lowering effect of the extract of black-soybean leaves (EBL), which mainly contains quercetin glycosides and isorhamnetin glycosides, in mice with high-fat-diet (HFD)-induced obesity and diabetes and in HepG2 cells. Twelve weeks of EBL supplementation decreased body weight and fasting glucose, glycated hemoglobin, insulin, triglyceride, and nonesterified fatty acid levels. Histological analyses manifested that EBL suppressed hepatic steatosis. Interestingly, EBL significantly improved plasma adiponectin levels and increased adiponectin-receptor-gene ( AdipoR1 and AdipoR2) expression in the liver. EBL restored the effects of HFD on hepatic AMP-activated protein kinase (AMPK) and on the family of peroxisome proliferator-activated receptors (PPARα, PPARδ, and PPARγ), which are associated with fatty acid metabolism and are downstream of the adiponectin receptors. Hence, EBL effectively diminished hyperglycemia and hepatic steatosis through enhancing adiponectin-induced signaling and AMPK activation in the liver.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Fígado Gorduroso/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Receptores de Adiponectina/metabolismo , Soja/química , Proteínas Quinases Ativadas por AMP/genética , Animais , Glicemia/metabolismo , Peso Corporal , Ácidos Graxos não Esterificados/metabolismo , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Humanos , Hiperglicemia/genética , Hiperglicemia/metabolismo , Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , PPAR alfa/genética , PPAR alfa/metabolismo , Folhas de Planta/química , Receptores de Adiponectina/genética , Transdução de Sinais , Triglicerídeos/metabolismo
16.
Sci Rep ; 8(1): 14339, 2018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-30254279

RESUMO

The knockout (KO) of the adiponectin receptor 1 (AdipoR1) gene causes retinal degeneration. Here we report that ADIPOR1 protein is primarily found in the eye and brain with little expression in other tissues. Further analysis of AdipoR1 KO mice revealed that these animals exhibit early visual system abnormalities and are depleted of RHODOPSIN prior to pronounced photoreceptor death. A KO of AdipoR1 post-development either in photoreceptors or the retinal pigment epithelium (RPE) resulted in decreased expression of retinal proteins, establishing a role for ADIPOR1 in supporting vision in adulthood. Subsequent analysis of the Mfrprd6 mouse retina demonstrated that these mice are lacking ADIPOR1 in their RPE layer alone, suggesting that loss of ADIPOR1 drives retinal degeneration in this model. Moreover, we found elevated levels of IRBP in both the AdipoR1 KO and the Mfrprd6 models. The spatial distribution of IRBP was also abnormal. This dysregulation of IRBP hypothesizes a role for ADIPOR1 in retinoid metabolism.


Assuntos
Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Receptores de Adiponectina/deficiência , Receptores de Adiponectina/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Visão Ocular , Animais , Proteínas do Olho/metabolismo , Humanos , Camundongos , Receptores de Adiponectina/genética , Retinoides/metabolismo , Proteínas de Ligação ao Retinol/metabolismo
17.
Mol Aspects Med ; 64: 18-33, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30244005

RESUMO

The functional significance of the selective enrichment of the omega-3 essential fatty acid docosahexaenoic acid (DHA; 22C and 6 double bonds) in cellular membrane phospholipids of the nervous system is being clarified by defining its specific roles on membrane protein function and by the uncovering of the bioactive mediators, docosanoids and elovanoids (ELVs). Here, we describe the preferential uptake and DHA metabolism in photoreceptors and brain as well as the significance of the Adiponectin receptor 1 in DHA retention and photoreceptor cell (PRC) survival. We now know that this integral membrane protein is engaged in DHA retention as a necessary event for the function of PRCs and retinal pigment epithelial (RPE) cells. We present an overview of how a) NPD1 selectively mediates preconditioning rescue of RPE and PR cells; b) NPD1 restores aberrant neuronal networks in experimental epileptogenesis; c) the decreased ability to biosynthesize NPD1 in memory hippocampal areas of early stages of Alzheimer's disease takes place; d) NPD1 protection of dopaminergic circuits in an in vitro model using neurotoxins; and e) bioactivity elicited by DHA and NPD1 activate a neuroprotective gene-expression program that includes the expression of Bcl-2 family members affected by Aß42, DHA, or NPD1. In addition, we highlight ELOVL4 (ELOngation of Very Long chain fatty acids-4), specifically the neurological and ophthalmological consequences of its mutations, and their role in providing precursors for the biosynthesis of ELVs. Then we outline evidence of ELVs ability to protect RPE cells, which sustain PRC integrity. In the last section, we present a summary of the protective bioactivity of docosanoids and ELVs in experimental ischemic stroke. The identification of early mechanisms of neural cell survival mediated by DHA-synthesized ELVs and docosanoids contributes to the understanding of cell function, pro-homeostatic cellular modulation, inflammatory responses, and innate immunity, opening avenues for prevention and therapeutic applications in neurotrauma, stroke and neurodegenerative diseases.


Assuntos
Doença de Alzheimer/genética , Ácidos Docosa-Hexaenoicos/genética , Inflamação/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Apoptose/genética , Ácidos Docosa-Hexaenoicos/metabolismo , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Ácidos Graxos Ômega-3/genética , Ácidos Graxos Ômega-3/metabolismo , Regulação da Expressão Gênica/genética , Humanos , Inflamação/metabolismo , Inflamação/patologia , Neuroproteção/genética , Células Fotorreceptoras/metabolismo , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia
18.
J Anim Physiol Anim Nutr (Berl) ; 102(6): 1585-1592, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30151936

RESUMO

Adiponectin is a circulatory cytokine secreted from adipose tissues and exerts critical metabolic functions in mammals. However, expression profiles of adiponectin and adiponectin receptors in the avian species that may be very different from mammals, especially under affluent nutrition conditions, remain unexplored to examine the effects of adiponectin and adiponectin receptors in chicken adipose tissues under high-fat diet (HFD) feeding. Twenty Taiwan country chickens (L2 bred) of 12 weeks old were challenged with a 10% high-fat diet for 6 weeks. Results showed that body weights and plasma triglycerides, cholesterol and dipeptidyl peptidase-4 (DPP4) were all increased in the HFD treatments. Interestingly, we first demonstrated that chicken circulating macromolecule adiponectin and fat disulphide-bond A oxidoreductase-like protein (DsbA-L), a regulator involved in adiponectin secretion, were elevated upon HFD feeding. Moreover, the mRNA expression of adiponectin and adiponectin receptors as well as additional adipose-related genes such as fatty acid synthase (FAS), adipose triglyceride lipase (ATGL), lipoprotein lipase (LPL), and peroxisome proliferator-activated receptor γ (PPARγ) were also increased in the chicken abdominal fats under HFD conditions. These results suggest that HFD treatment alters adiponectin and metabolic genes in chicken adipose tissues. In conclusion, in the present study, we examine expression profiles of adiponectin, adiponectin receptors, adiponectin secretion regulator DsbA-L, and metabolic genes in chicken fats upon HFD supplementation and provide new insights for how adiponectin entail the pathophysiologically obesogenic conditions in the avian species.


Assuntos
Adiponectina/metabolismo , Ração Animal/análise , Galinhas/metabolismo , Dieta/veterinária , Regulação da Expressão Gênica/efeitos dos fármacos , Receptores de Adiponectina/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , Colesterol/sangue , Dieta Hiperlipídica , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , Receptores de Adiponectina/genética , Transcriptoma , Triglicerídeos/sangue
19.
J Neuroinflammation ; 15(1): 215, 2018 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30060752

RESUMO

BACKGROUND: Neuroinflammation is a crucial factor contributing to neurological injuries after intracerebral hemorrhage (ICH). C1q/TNF-related protein 9 (CTRP9), an agonist of adiponectin receptor 1 (AdipoR1), has recently been shown to reduce inflammatory responses in systemic diseases. The objective of this study was to investigate the protective role of CTRP9 against neuroinflammation after ICH in a mouse model and to explore the contribution of adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor kappa B (NFκB) pathway in AdipoR1-mediated protection. METHODS: Adult male CD1 mice (n = 218) were randomly assigned to different groups for the study. ICH was induced via intrastriatal injection of bacterial collagenase. Recombinant CTRP9 (rCTRP9) was administered intranasally at 1 h after ICH. To elucidate the underlying mechanism, AdipoR1 small interfering ribonucleic acid (siRNA) and selective phosphorylated AMPK inhibitor Dorsomorphin were administered prior to rCTRP9 treatment. Brain edema, short- and long-term neurobehavior evaluation, blood glucose level, western blot, and immunofluorescence staining were performed. RESULTS: Endogenous CTRP9 and AdipoR1 expression was increased and peaked at 24 h after ICH. AdipoR1 was expressed by microglia, neurons, and astrocytes. Administration of rCTRP9 reduced brain edema, improved short- and long-term neurological function, enhanced the expression of AdipoR1 and p-AMPK, and decreased the expression of phosphorylated NFκB and inflammatory cytokines after ICH. The protective effects of rCTRP9 were abolished by administration of AdipoR1 siRNA and Dorsomorphin. CONCLUSIONS: Our findings demonstrated that administration of rCTRP9 attenuated neuroinflammation through AdipoR1/AMPK/NFκB signaling pathway after ICH in mice, thereby reducing brain edema and improving neurological function after experimental ICH in mice. Therefore, CTRP9 may provide a potential therapeutic strategy to alleviate neuroinflammation in ICH patients.


Assuntos
Adiponectina/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Hemorragia Cerebral/complicações , Encefalite/tratamento farmacológico , Encefalite/etiologia , Glicoproteínas/administração & dosagem , Receptores de Adiponectina/metabolismo , Adiponectina/metabolismo , Animais , Edema Encefálico/etiologia , Hemorragia Cerebral/mortalidade , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Glicoproteínas/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Equilíbrio Postural/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Receptores de Adiponectina/genética , Proteínas Recombinantes/administração & dosagem , Resultado do Tratamento
20.
Food Res Int ; 112: 48-55, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30131158

RESUMO

The study investigated the effect of extruded sorghum flour (ESF) in a high fat diet (HFD) on biometric measurements and hepatic lipogenesis. Male Wistar rats were fed a normal diet (AIN-93M), HFD, HFD plus ESF replacing 50% cellulose and 100% corn starch (HFDS50), or HFD plus ESF replacing 100% cellulose and 100% corn starch (HFDS100) for eight weeks. ESF reduced the body mass index and liver weight of obese rats. Additionally, ESF reduced hepatic lipogenesis by increasing adiponectin 2 receptor gene expression and gene and protein expressions of peroxisome proliferator-activated receptor α (PPARα), while reducing the gene expression of sterol regulatory element-binding transcription factor 1. Molecular docking analysis revealed the affinity of ESF compounds (luteolinidin, apigeninidin, 5-methoxy-luteolinidin, and 7-methoxy-apigeninidin) with the PPAR-α receptor. Histological analysis confirmed the decreased grade of hepatic steatosis in obese rats. These data indicate the potential of ESF to reduce metabolic risk of hepatic steatosis associated with lipogenesis and obesity.


Assuntos
Ração Animal , Dieta Hiperlipídica , Fígado Gorduroso/prevenção & controle , Farinha , Lipogênese , Fígado/metabolismo , Obesidade/dietoterapia , Sorghum , Animais , Modelos Animais de Doenças , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Regulação da Expressão Gênica , Fígado/patologia , Masculino , Simulação de Acoplamento Molecular , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Tamanho do Órgão , PPAR alfa/genética , PPAR alfa/metabolismo , Ratos Wistar , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Fatores de Tempo , Perda de Peso
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA