RESUMO
BACKGROUND: The disruption of the blood brain barrier (BBB) is the key factor leading to neurological impairment after intracerebral hemorrhage (ICH) injury. Adiponectin receptor 1 (AdipoR1) has an important effect contributing to the integrity of BBB. As a homologue of adiponectin, recombinant C1q/TNF-related protein 9 (rCTRP9) has neuroprotective effect in cerebrovascular diseases. The aim of this study was to investigate the protective effect of AdipoR1 activation with rCTRP9 on BBB integrity after ICH injury and the potential mechanisms. METHODS: 177 male mice were subjected in this study. ICH was induced by injecting collagenase into the right basal ganglia. rCTRP9 was treated intranasally at 1 hour after ICH. Selective siRNA was administered prior to ICH. Western blot, immunofluorescence staining, neurobehavioral tests, and BBB permeability were evaluated. RESULTS: ICH increased the expression of endogenous AdipoR1 and CTRP9. Administration of rCTRP9 ameliorated neurological deficits and reduced the BBB permeability at 24 hours in ICH mice. Furthermore, rCTRP9 promoted the expression of AdipoR1, APPL1, p-AMPK, Nrf2, and tight junctional proteins. The intervention of specific siRNA of AdipoR1, APPL1, and p-AMPK reversed the protective effects of rCTRP9. CONCLUSIONS: Activation of AdipoR1 with rCTRP9 improved neurological functions and preserved BBB integrity through the APPL1/AMPK/Nrf2 signaling pathway in ICH mice. Therefore, CTRP9 could serve as a promising therapeutic method to alleviate BBB injury following ICH in patients.
Assuntos
Adiponectina/administração & dosagem , Barreira Hematoencefálica/efeitos dos fármacos , Hemorragia Cerebral/prevenção & controle , Regulação da Expressão Gênica/efeitos dos fármacos , Glicoproteínas/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Receptores de Adiponectina/agonistas , Proteínas Recombinantes/administração & dosagem , Quinases Proteína-Quinases Ativadas por AMP/genética , Quinases Proteína-Quinases Ativadas por AMP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Permeabilidade da Membrana Celular , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/patologia , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de SinaisRESUMO
CONTEXT: Human milk contains hormones that regulate metabolism. Extrauterine growth restriction remains common among preterm infants, but the effect of ingesting milk hormones on preterm infant growth is poorly understood. OBJECTIVE: To quantify associations of longitudinal exposure to leptin, adiponectin, and insulin in milk with physical growth of preterm infants. DESIGN/METHODS: In 50 preterm neonates (median gestational age 29.4 weeks), we sampled maternal milk on day-of-life 7, 14, 21, and 28 and measured hormone levels in whole milk by ELISA. Milk leptin levels were available for a subset of 18 infants. We calculated milk hormone doses by multiplying the hormone level by the milk volume ingested on each day and estimated the area under the curve (AUC) to reflect longitudinal exposure. We analyzed associations of milk hormone exposure with growth outcomes in generalized estimated equations. MAIN OUTCOME MEASURES: Weight gain velocity and z-scores in weight, length, head circumference, and body mass index at 36 weeks' postmenstrual age (PMA). RESULTS: Higher leptin intake was associated with greater weight gain (2.17g/kg/day [95% CI, 1.31, 3.02]) and weight z-score at 36 weeks' PMA (0.30 [0.08, 0.53] higher z-score per tertile). Higher adiponectin intake was associated with greater length z-score (0.41 [0.13, 0.69]), however, this association was nullified after adjustment of protein and calorie intake. Higher adiponectin was associated with smaller head circumference z-score (-0.36 [-0.64, -0.07]). Insulin was not associated with growth outcomes. CONCLUSIONS: Milk leptin and adiponectin exposures may affect growth of preterm infants. The long-term effects of milk hormones warrant further investigation.
Assuntos
Desenvolvimento Infantil/fisiologia , Ingestão de Alimentos/fisiologia , Hormônios/administração & dosagem , Leite Humano/fisiologia , Adiponectina/administração & dosagem , Adiponectina/metabolismo , Estudos de Coortes , Feminino , Hormônios/metabolismo , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Leptina/administração & dosagem , Leptina/metabolismo , Estudos Longitudinais , Masculino , Massachusetts , Leite Humano/química , Leite Humano/metabolismo , Aumento de Peso/fisiologiaRESUMO
PURPOSE: Obstructive sleep apnea hypopnea syndrome has been reported to be associated with pulmonary hypertension (PH). Adiponectin (Ad) has many protective roles in the human body, including its function as an anti-inflammatory and an anti-oxidant, as well as its role in preventing insulin resistance and atherosclerosis. This study aimed to investigate the molecular mechanism of chronic intermittent hypoxia (CIH)-induced pulmonary injury and the protective role of Ad in experimental rats. METHODS: Thirty male Sprague-Dawley rats were randomly divided into three groups with 10 rats in each group: normal control (NC) group, CIH group, and CIH + Ad group. Rats in the NC group were kept breathing room air for 12 weeks. Rats in the CIH group were intermittently exposed to a hypoxic environment for 8 h/day for 12 weeks. Rats in the CIH + Ad group received 10 µg Ad twice weekly via intravenous injection. After 12 weeks of CIH exposure, we detected the pulmonary function, pulmonary artery pressure, lung histology, pulmonary cell apoptosis, pulmonary artery endothelial cell apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) level. We also analyzed expression proteins involved in the mitochondria-, endoplasmic reticulum (ER) stress-, and Fas receptor-associated pulmonary apoptosis pathways, as well as the SIRT3/SOD2 pathway. RESULTS: CIH exposure for 12 weeks did not lead to abnormal pulmonary function, PH, or pulmonary artery endothelial cell apoptosis. However, we observed a significant increase in the rate of pulmonary cell apoptosis, the expression of proteins involved in mitochondria-, ER stress-, and Fas receptor-associated pulmonary apoptosis pathways, and the generation of ROS in the CIH group compared with the NC group. In contrast, the MMP and protein expressions of SIRT3/SOD2 pathway were significantly decreased in the CIH group compared with the NC group. Ad supplementation in the CIH + Ad group partially improved these changes induced by CIH. CONCLUSION: Even though CIH did not cause abnormal pulmonary function or PH, early lung injury was detected at the molecular level in rats exposed to CIH. Treatment with Ad ameliorated the pulmonary injury by activating the SIRT3/SOD2 pathway, reducing ROS generation, and inhibiting ROS-associated lung cell apoptosis.
Assuntos
Adiponectina/farmacologia , Apoptose/efeitos dos fármacos , Hipóxia/complicações , Lesão Pulmonar/etiologia , Espécies Reativas de Oxigênio/metabolismo , Adiponectina/administração & dosagem , Animais , Western Blotting , Injeções Intravenosas , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiopatologia , Lesão Pulmonar/prevenção & controle , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
A loss-of-function mutation in the Lrp5 gene in mice leads to a low bone mass disorder due to the inhibition of the canonical Wnt signaling pathway; however, the role of bone marrow microenvironment in mice with this mutation remains unclear. In this study, we evaluated proliferation and osteogenic potential of mouse osteoblasts using the MTT assay and Alizarin red staining. The levels of alkaline phosphatase, tartrate-resistant acid phosphatase, and adiponectin in culture supernatants were measured using the enzyme-linked immunosorbent assay. Osteoclast bone resorbing activity was evaluated by toluidine staining and the number and area of bone resorption pits were determined. We observed increased osteogenesis in osteoblasts co-cultured with the BM-derived myeloid cells compared to the osteoblasts cultured alone. Mice with global Lrp5 deletion had a relatively higher bone density compared to the mice carrying osteoblast/osteocyte-specific Lrp5 deletion. An increased frequency of M2 macrophages and reduced expression of inflammatory cytokines were detected in the myeloid cells derived from the bone marrow of mice with global Lrp5 deletion. Higher adipogenic potential and elevated levels of adiponectin in the global Lrp5 deletion mice contributed to the preferential M2 macrophage polarization. Here, we identified a novel systemic regulatory mechanism of bone formation and degradation in mice with global Lrp5 deletion. This mechanism depends on a crosstalk between the adipocytes and M2 macrophages in the bone marrow and is responsible for partly rescuing osteopenia developed as a result of decreased Wnt signaling.
Assuntos
Adipócitos/patologia , Doenças Ósseas Metabólicas/patologia , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/deficiência , Macrófagos/patologia , Adipócitos/metabolismo , Adiponectina/administração & dosagem , Adiponectina/metabolismo , Animais , Células da Medula Óssea/patologia , Osso e Ossos/patologia , Diferenciação Celular , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Macrófagos/metabolismo , Camundongos , Células Mieloides/metabolismo , Células Mieloides/patologia , Tamanho do Órgão , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteogênese , Osteoporose/patologia , FenótipoRESUMO
OBJECTIVE: To investigate the influences of adiponectin (APN) on the liver injury in sepsis rats and to explore whether it exerts a therapeutic effect through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. MATERIALS AND METHODS: A rat model of sepsis was established through cecal ligation and puncture (CLP) (CLP group), and APN treatment group (APN group) and control group were also set. The changes in the liver function-related indicators, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were determined by automatic biochemistry analyzer, and the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1, and IL-6 were measured via enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was employed to detect liver tissue injury, and the hepatocyte apoptosis and necrosis after intervention with APN were evaluated using in situ fluorescence staining. Moreover, the mRNA expression of APN in liver tissues was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), and the expression levels of phosphorylated AMPK and mTOR proteins in liver tissue samples were determined using Western blotting. RESULTS: In terms of changes in liver function-related indicators, the concentrations of ALT and AST were substantially raised in the CLP group, and compared with those in the control group, the concentrations of the two indicators significantly declined in the APN group, showing statistically significant differences (p<0.05). CLP and APN group had evidently higher levels of inflammatory factors than the control group, but their levels in APN group were notably lower than those in the CLP group (p<0.05). It was found through the HE staining that the sepsis rats in CLP group had massive inflammatory cell infiltration, and that the inflammatory cells were remarkably decreased in the APN group after APN treatment. According to the in-situ fluorescence staining detection results, CLP group exhibited a notable increase in the cell apoptosis rate, and APN group had substantially reduced apoptotic cells (p<0.05). The determination results of APN expression revealed that CLP group had a lowered level of APN, and that the level of APN in APN group was markedly higher than that in the control group. Based on the results of Western blotting, the level of phosphorylated AMPK was remarkably elevated, and that of phosphorylated mTOR was lowered in the CLP group compared with those in the control group, while in comparison with CLP group, APN group showed a considerable elevation of phosphorylated AMPK level and a distinct decline in the phosphorylated mTOR level. CONCLUSIONS: APN can activate the AMPK/mTOR pathway and reduce hepatocyte apoptosis to alleviate liver injury in sepsis rats.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/farmacologia , Fígado/efeitos dos fármacos , Sepse/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Adiponectina/administração & dosagem , Animais , Modelos Animais de Doenças , Injeções Intraperitoneais , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Sepse/metabolismo , Sepse/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Reports in recent years have suggested that adiponectin (APN) improves insulin resistance and inhibits apoptosis by activating the AMP-activated protein kinase (AMPK) pathway and the PI3K/Akt signaling pathway after binding to its receptor. This study aims to explore the mechanism by which APN reduces embryo loss rate and trophoblast apoptosis in early pregnancy of mice with polycystic ovary syndrome (PCOS). PCOS mice were subcutaneously injected with APN (10 µg mg kg-1 day-1) on 11 consecutive days from the 3rd day of pregnancy onwards to observe the change of the embryo loss rate of PCOS mice induced by APN. Quantitative real-time PCR and Western blot were used to determine the relative expressions of mRNA and the proteins AMPK, PI3K, and Akt in mouse uterine tissue. At the same time, primary cultured mouse villous trophoblast cells were used to further explore the underlying mechanisms in vitro. APN significantly reduces the pregnancy loss rate of PCOS mice. At the same time, APN increases phosphorylation and mRNA expression levels of AMPK, PI3K, and Akt in PCOS mouse uterine tissue. In addition, trophoblast cells of model mice were treated with APN and inhibitors, and APN was found to reduce trophoblast cell apoptosis by affecting the phosphorylation levels of AMPK, PI3K, Akt, and FoxO3a proteins. APN reduces the embryo loss rate and ameliorates trophoblast apoptosis in PCOS mice by affecting the AMPK/PI3K/AKT/FoxO3a signaling pathway.
Assuntos
Adiponectina/metabolismo , Apoptose , Síndrome do Ovário Policístico/metabolismo , Transdução de Sinais , Trofoblastos/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Feminino , Proteína Forkhead Box O3/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Trofoblastos/efeitos dos fármacosRESUMO
This review describes the multifaceted effects of adiponectin on breast cancer cell signalling, tumour metabolism, and microenvironment. It is largely documented that low adiponectin levels are associated with an increased risk of breast cancer. However, it needs to be still clarified what are the extents of the decrease of local/intra-tumoural adiponectin concentrations, which promote breast tumour malignancy. Most of the anti-proliferative and pro-apoptotic effects induced by adiponectin have been obtained in breast cancer cells not expressing estrogen receptor alpha (ERα). Here, we will highlight recent findings demonstrating the mechanistic effects through which adiponectin is able to fuel genomic and non-genomic estrogen signalling, inhibiting LKB1/AMPK/mTOR/S6K pathway and switching energy balance. Therefore, it emerges that the reduced adiponectin levels in patients with obesity work to sustain tumour growth and progression in ERα-positive breast cancer cells. All this may contribute to remove the misleading paradigm that adiponectin univocally inhibits breast cancer cell growth and progression independently on ERα status. The latter concept, here clearly provided by pre-clinical studies, may have translational relevance adopting adiponectin as a potential therapeutic tool. Indeed, the interfering role of ERα on adiponectin action addresses how a separate assessment of adiponectin treatment needs to be considered in novel therapeutic strategies for ERα-positive and ERα-negative breast cancer.
Assuntos
Adiponectina/fisiologia , Neoplasias da Mama/fisiopatologia , Receptor alfa de Estrogênio/fisiologia , Adiponectina/administração & dosagem , Adiponectina/deficiência , Neoplasias da Mama/etiologia , Neoplasias da Mama/patologia , Proliferação de Células , Receptor alfa de Estrogênio/análise , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Sistema Imunitário , Obesidade/complicações , Obesidade/fisiopatologia , Fatores de Risco , Transdução de SinaisRESUMO
BACKGROUND/OBJECTIVES: Adiponectin concentrations are low in obese pregnant women. Restoring normal adiponectin concentrations by infusion in obese pregnant mice prevents placental dysfunction, foetal overgrowth and metabolic syndrome in the offspring. We hypothesised that normalising maternal adiponectin in obese late pregnant dams prevents cardiac dysfunction in the adult offspring. SUBJECTS/METHODS: Pregnant female mice with diet-induced obesity were infused with adiponectin (0.62 µg g-1 day-1, n = 24) or saline (n = 22) over days 14.5-18.5 of pregnancy (term = day 19.5). Control dams ate standard chow and received saline (n = 22). Offspring were studied at 3 and 6 months of age. RESULTS: Maternal obesity impaired ventricular diastolic function, increased cardiomyocyte cross-sectional area and upregulated cardiac brain natriuretic peptide (Nppb) and α-skeletal actin (Acta1) gene expression in adult male offspring, compared to control offspring. In adult female offspring, maternal obesity increased Nppb expression, decreased end-diastolic volume and caused age-dependent diastolic dysfunction but not cardiomyocyte hypertrophy. Maternal obesity also activated cardiac Akt and mechanistic target of rapamycin (mTOR) signalling in male, but not in female, offspring and inhibited cardiac extracellular signal-regulated kinase 1/2 (ERK1/2) in both sexes. Normalising maternal circulating adiponectin concentrations by infusing obese dams with adiponectin prevented offspring diastolic dysfunction and ventricular dilation and normalised cardiac Akt-mTOR signalling irrespective of sex. Maternal adiponectin infusion also reduced cardiac Nppb expression and increased ERK1/2 signalling in offspring of obese dams. Adiponectin infusion did not prevent cardiomyocyte hypertrophy but reduced ventricular wall thickness in male offspring and increased collagen content in female offspring of obese dams, compared to controls. CONCLUSIONS: Low maternal adiponectin levels in obese mice in late pregnancy are mechanistically linked to in utero programming of cardiac dysfunction in their offspring. Interventions enhancing endogenous adiponectin secretion or signalling in obese pregnant women could prevent the development of cardiac dysfunction in their children.
Assuntos
Adiponectina , Cardiopatias/prevenção & controle , Fenômenos Fisiológicos da Nutrição Materna/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Adiponectina/administração & dosagem , Adiponectina/sangue , Adiponectina/farmacologia , Animais , Ecocardiografia , Feminino , Coração/diagnóstico por imagem , Coração/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Miocárdio/patologia , GravidezRESUMO
Purpose: To evaluate the efficacy of adiponectin (APN)-derived short peptides (ADPs) 355 compared with globular APN in a mouse model of experimental dry eye (EDE) and corneal alkali burn. Methods: EDE and chemical burn were induced in C57BL/6 mice by desiccating stress and application of NaOH, respectively. Eye drops consisting of 0.01% globular APN, 0.01% ADPs, 0.1% ADPs, or balanced salt solution (BSS) were applied. Tear volume, tear film break-up time, and corneal staining scores were measured. Concentrations of interleukin (IL)-1ß, interferon (IFN)-γ, IL-6, CXCL-9, and CXCL-10 using multiplex immunobead assay were evaluated, and flow cytometry were performed. Corneal epithelial defects and haze degree were analyzed, and enzyme-linked immunosorbent assay for IL-1ß and transforming growth factor (TGF)-ß levels were observed. Results: All treatment groups showed an improvement in clinical parameters and CD4+CCR5+ T cell and CD11b+ cell infiltrations in the conjunctiva (all P < 0.05). Both ADPs groups had significantly decreased concentrations of IL-1ß, IFN-γ, IL-6, CXCL-9, and CXCL-10 in the conjunctiva than the EDE or BSS group. Significantly improved parameters of epithelial defect, degree of haze, and concentrations of IL-1ß and TGF-ß were observed in all treatment groups. However, no significant differences were noted in clinical or experimental parameters among treatment groups. Conclusion: Topical ADPs could effectively improve clinical signs and inflammation of ocular surface in the EDE or alkali burn, and its efficacy and potency were similar to those of globular APN.
Assuntos
Adiponectina/uso terapêutico , Queimaduras Químicas/tratamento farmacológico , Síndromes do Olho Seco/tratamento farmacológico , Queimaduras Oculares/tratamento farmacológico , Soluções Oftálmicas/uso terapêutico , Peptídeos/uso terapêutico , Adiponectina/administração & dosagem , Administração Tópica , Animais , Queimaduras Químicas/metabolismo , Modelos Animais de Doenças , Síndromes do Olho Seco/metabolismo , Queimaduras Oculares/induzido quimicamente , Queimaduras Oculares/metabolismo , Feminino , Injeções Subcutâneas , Camundongos , Camundongos Endogâmicos C57BL , Soluções Oftálmicas/administração & dosagem , Peptídeos/administração & dosagem , Hidróxido de SódioRESUMO
Diastolic dysfunction is common in various cardiovascular diseases, which could be affected by adiponectin (APN). Nevertheless, the effects of APN on diastolic dysfunction in pressure overload model induced by transverse aorta constriction (TAC) remain to be further elucidated. Here, we demonstrated that treatment of APN attenuated diastolic dysfunction and cardiac hypertrophy in TAC mice. Notably, APN also improved active relaxation of adult cardiomyocytes, increased N2BA/N2B ratios of titin isoform, and reduced collagen type I to type III ratio and lysyl oxidase (Lox) expressions in the myocardial tissue. Moreover, APN supplementation suppressed TAC-induced oxidative stress. In vitro, inhibition of AMPK by compound C (Cpc) abrogated the effect of APN on modulation of titin isoform shift and the anti-hypertrophic effect of APN on cardiomyocytes induced by AngII. In summary, our findings indicate that APN could attenuate diastolic dysfunction in TAC mice, which are at least partially mediated by AMPK pathway.
Assuntos
Adiponectina/administração & dosagem , Hipertrofia Ventricular Esquerda/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Disfunção Ventricular Esquerda/prevenção & controle , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células Cultivadas , Diástole , Modelos Animais de Doenças , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Fibrose , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estresse Oxidativo , Proteínas Quinases/metabolismo , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
Decreased mineral density is one of the major complications of anorexia nervosa. The phenomenon is even more pronounced when the disease occurs during adolescence and when the duration of amenorrhoea is long. The mechanisms underlying bone loss in anorexia are complex. Oestrogen deficiency has long been considered as the main factor, but cannot explain the phenomenon on its own. The essential role of nutrition-related factors-especially leptin and adiponectin-has been reported in recent studies. Therapeutic strategies to mitigate bone involvement in anorexia are still a matter for debate. Although resumption of menses and weight recovery appear to be essential, they are not always accompanied by a total reversal of bone loss. There are no studies in the literature demonstrating that oestrogen treatment is effective, and the best results seem to have been obtained with agents that induce bone formation-such as IGF-1-especially when associated with oestrogen. As such, bone management in anorexia remains difficult, hence, the importance of early detection and multidisciplinary follow-up.
Assuntos
Amenorreia/complicações , Anorexia Nervosa/complicações , Densidade Óssea/fisiologia , Osteoporose/terapia , Absorciometria de Fóton , Adiponectina/administração & dosagem , Adiponectina/deficiência , Amenorreia/metabolismo , Anorexia Nervosa/diagnóstico , Anorexia Nervosa/metabolismo , Anorexia Nervosa/reabilitação , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Quimioterapia Combinada , Estrogênios/administração & dosagem , Estrogênios/metabolismo , Exercício Físico/fisiologia , Feminino , Humanos , Fator de Crescimento Insulin-Like I/administração & dosagem , Leptina/administração & dosagem , Leptina/deficiência , Lipólise/efeitos dos fármacos , Osteoporose/diagnóstico , Osteoporose/etiologia , Osteoporose/metabolismo , Proteínas Recombinantes/administração & dosagem , Resultado do Tratamento , Aumento de Peso/fisiologiaRESUMO
Objective:The aim of this study is to analyze the effects of glutathione on oxidative stress, leptin and adiponectin in patients with obstructive sleep apneaï¼OSAï¼ complicated with metabolic syndrome. Method:One hundred and fifty-nine patients with OSA and MS were enrolled in the group A according to the exclusion criteria. One hundred and fifty-nine patients with MS group were not included in the OSA group, and 159 patients were included in the control group. Before and after treatment, the levels of serum malondialdehyde ï¼MDAï¼, superoxide dismutase ï¼SODï¼, Leptin and ADP were respectively detected, and the clinical effects of the three groups were compared. Result:Compared with the control group, the contents of MDA and Leptin in the case A and B groups were significantly higher than that of the control group, and the contents of SOD and ADP were significantly lower than that of the control group, and the difference was statistically significant, especially in case group A. The level of SOD and ADP was significantly higher in the group after treatment than before treatment, and the level of MDA and Leptin was significantly lower than before treatment. The difference was statistically significant, especially in case group A, too. Conclusion:Patients with OSA and MS are associated with oxidative stress. Glutathione can effectively improve the body's ability to resist oxidative stress, reduce oxidative damage, reduce leptin, and increase ADP levels.
Assuntos
Adiponectina/administração & dosagem , Glutationa/farmacologia , Leptina/administração & dosagem , Síndrome Metabólica/complicações , Estresse Oxidativo , Apneia Obstrutiva do Sono/sangue , Estudos de Casos e Controles , Humanos , Malondialdeído/sangue , Apneia Obstrutiva do Sono/complicações , Superóxido Dismutase/sangueRESUMO
OBJECTIVE: To determine effects of hydrocortisone administration on serum leptin and adiponectin concentrations, abdominal fat distribution, and mRNA expression of leptin and adiponectin in abdominal adipose tissue of dogs. ANIMALS: 12 healthy dogs. PROCEDURES: Dogs received hydrocortisone (8.5 mg/kg; n = 6) or a placebo (6) orally every 12 hours for 90 days. Serum leptin and adiponectin concentrations were measured with a canine-specific ELISA on the day before (day 0; baseline) and during (days 1, 3, 7, 30, 60, and 90) administration. On days 0, 30, 60, and 90, abdominal fat mass was quantified with CT, and mRNA expression of leptin and adiponectin in abdominal fat was analyzed by use of a PCR assay. RESULTS: Hydrocortisone administration resulted in an increase in visceral fat mass on days 60 and 90, compared with the mass at baseline. Visceral fat mass at the level of L3 increased during hydrocortisone administration. Serum leptin concentration began to increase on day 1 and was significantly higher than the baseline concentration on days 30 and 60. Serum adiponectin concentration on days 30, 60, and 90 was significantly lower than the baseline concentration. Leptin and adiponectin mRNA expression in abdominal fat was greater on day 30, compared with expression at baseline, but lower on days 60 and 90, compared with expression on day 30. Serum leptin concentration and visceral fat mass were correlated. CONCLUSIONS AND CLINICAL RELEVANCE: Hydrocortisone administration affected abdominal fat distribution and serum leptin and adiponectin concentrations through dysregulation of leptin and adiponectin expression.
Assuntos
Adiponectina/biossíntese , Cães , Hidrocortisona/farmacologia , Leptina/biossíntese , Adiponectina/administração & dosagem , Tecido Adiposo/metabolismo , Administração Oral , Animais , Hidrocortisona/administração & dosagem , Masculino , Biossíntese de Proteínas/efeitos dos fármacos , Distribuição AleatóriaRESUMO
Comprehensive understanding of the regulatory mechanism of the implantation process in pigs is crucial for reproductive success. The endometrium plays an important role in regulating the establishment and maintenance of gestation. The goal of the current study was to determine the effect of adiponectin on the global expression pattern of genes and relationships among differentially expressed genes (DE-genes) in the porcine endometrium during implantation using microarrays. Diverse transcriptome analyses including gene ontology (GO), biological pathway, networks, and DE-gene analyses were performed. Adiponectin altered the expression of 1286 genes with fold-change (FC) values greater than 1.2 (p < 0.05). The expression of 560 genes were upregulated and 726 downregulated in the endometrium treated with adiponectin. Thirteen genes were selected for real-time PCR validation of differential expression based on a known role in metabolism, steroid and prostaglandin synthesis, interleukin and growth factor action, and embryo implantation. Functional analysis of the relationship between DE-genes indicated that adiponectin interacts with genes that are involved in the processes of cell proliferation, programmed cell death, steroid and prostaglandin synthesis/metabolism, cytokine production, and cell adhesion that are critical for reproductive success. The presented results suggest that adiponectin signalling may play a key role in the implantation of pig.
Assuntos
Adiponectina/administração & dosagem , Endométrio/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Proteínas/química , Transcriptoma/genética , Adiponectina/genética , Animais , Proliferação de Células/efeitos dos fármacos , Endométrio/química , Endométrio/crescimento & desenvolvimento , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Análise de Sequência com Séries de Oligonucleotídeos , Gravidez/genética , Gravidez/fisiologia , Dobramento de Proteína/efeitos dos fármacos , Reprodução/genética , Suínos/genéticaRESUMO
Leptin and adiponectin, adipokines present in breast milk, have shown immunomodulatory properties. The current study aimed to ascertain whether a nutritional supplementation with leptin or adiponectin in neonatal rats was able to influence the maturation of the systemic immune response in early life. To achieve this, suckling Wistar rats were supplemented with either leptin (0.7 µg/kg/day) or adiponectin (35 µg/kg/day) during the whole suckling period. Plasmatic immunoglobulins were quantified, and spleen lymphocyte composition and their ability to proliferate and release cytokines were evaluated during (day 14) and at the end (day 21) of the suckling period. Rats fed with either adipokine showed higher plasma IgM and IgG1 concentrations and adiponectin supplementation also increased IgG2a at both studied days (P < 0.05). With regard to the lymphocyte composition, both adipokine supplementations increased T cell proportion and both CD4+ and CD8+ T cell subsets after two weeks of supplementation (P < 0.05). Moreover, only leptin administration increased NK and NKT cell proportions at the end of the suckling period. Finally, both adipokines influenced the cytokine secretion pattern by splenocytes. In conclusion, these results suggest that leptin and adiponectin play a role in the maturation of the systemic immune response during the suckling period.
Assuntos
Adiponectina/administração & dosagem , Animais Lactentes/imunologia , Suplementos Nutricionais , Leptina/administração & dosagem , Animais , Peso Corporal , Citocinas/metabolismo , Imunoglobulinas/sangue , Imunoglobulinas/metabolismo , Tamanho do Órgão , Ratos , Ratos Wistar , Baço/metabolismo , Subpopulações de Linfócitos T , Timo/metabolismoRESUMO
Adiponectin (Acrp30) plays an important role in energy metabolism and inflammation. Recently, in vivo serum Acrp30 levels have been reported to be correlated to risk of developing several types of cancers such as lung cancer, and in vitro studies have demonstrated a role for Acrp30 in the control of cell proliferation and survival. However, the molecular effects of Acrp30 on lung cancer have not yet been clearly defined. In the present study, we investigated the effects of different concentrations of Acrp30 on the A549 human alveolar epithelial cell line, an in vitro model of lung adenocarcinoma. A549 cells were exposed to various concentrations of Acrp30 and successively, proliferation, apoptosis and oxidative stress were evaluated by MTT test, caspase activity assay, flow-cytometry and western blotting analysis. Our results demonstrated that Acrp30 causes, in a time- and dose-dependent manner, a reduction of cell viability and duplication together with an increase in cell apoptosis rate. In addition, we found that Acrp30 induces an increase of lipid peroxidation evaluated by TBARS assay and a concomitant reduction of nitric oxide release, both markers of cellular oxidative stress. Taken together, our data on A549â¯cells provides new insight into potential involvement of Acrp30 on physio-pathologic mechanisms of lung diseases through interference with proliferation, apoptosis and oxidative status.
Assuntos
Adenocarcinoma de Pulmão/patologia , Adiponectina/metabolismo , Neoplasias Pulmonares/patologia , Estresse Oxidativo , Células A549 , Adiponectina/administração & dosagem , Apoptose/efeitos dos fármacos , Western Blotting , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Citometria de Fluxo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Fatores de TempoRESUMO
BACKGROUND/AIM: Adiponectin is accepted as playing pivotal roles in the development of allergic rhinitis (AR) through modulation of production of inflammatory mediators. Although it is also well known that neuropeptides, especially substance P (SP), function in the development and persistence of clinical conditions of AR, the influence of adiponectin on neuropeptide production is not well understood. The present study was designed to examine the influence of adiponectin on the production of SP both in vivo and in vitro. MATERIALS AND METHODS: PC-12 cells (1×104 cells) were stimulated with 10.0 ng/ml nerve growth factor (NGF) for 2 h and then with 10.0 ng/ml capsaicin in the presence of different concentrations of adiponectin. After 72 h, culture supernatants were obtained, and SP levels were measured with enzyme-linked immunosorbent assay (ELISA). The influence of adiponectin on the total number of neurites developed per PC-12 cell and on the percentage of PC-12 cells with outgrowing neurites was also examined 24 and 72 h after the start of culture, respectively. In the second part of the study, BALB/c mice were sensitized intraperitoneally with 1.0 µg of ovalbumin and then challenged with intranasal ovalbumin. At 7 days following sensitization, these mice were treated with different doses of adiponectin intranasally in a volume of 5.0 µl. Nasal allergy-like symptoms, which were induced by bilateral application of 0.1 % OVA (5.0 µl), were assessed by counting sneezing and nasal rubbing behavior for 10 min immediately after nasal ovalbumin challenge. SP levels in nasal lavage fluid obtained 6 h after nasal ovalbumin challenge were examined by ELISA. RESULTS: Treatment of NGF-stimulated PC-12 cells with adiponectin suppressed SP production, which was induced by capsaicin stimulation. The minimum concentration of adiponectin that caused significant suppression was 7.5 ng/ml. On the other hand, adiponectin did not affect the total number of neurites and the percentage of PC-12 cells with outgrowing neurites, even at 1,000 ng/ml. Intranasal instillation of adiponectin into ovalbumin-sensitized mice at more than 10.0 ng/ml, but not 5.0 ng/ml, significantly inhibited the appearance of SP in nasal secretions, which was increased by intranasal challenge with ovalbumin. Adiponectin also suppressed the development of nasal allergic-like symptoms, sneezing and rubbing behavior, when ovalbumin-sensitized mice were treated intranasally with adiponectin at more than 10.0 ng/ml. The present results strongly suggested that adiponectin suppresses the production of SP and results in improvement of the clinical conditions of AR.
Assuntos
Adiponectina/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/genética , Adiponectina/genética , Administração Intranasal , Animais , Capsaicina/administração & dosagem , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Mucosa Nasal/efeitos dos fármacos , Neuritos/efeitos dos fármacos , Ratos , Proteínas Recombinantes/genética , Rinite Alérgica/patologiaRESUMO
Central adiponectin (APN) in either the globular (gAPN) or full-length forms decreases sympathetic tone and increases trabecular bone mass in mice through the hypothalamus. It is known that cannabinoid type-1 (CB1) receptors are expressed in the hypothalamic ventromedial nucleus and participate in energy metabolism by controlling sympathetic activity. However, whether central APN could influence endocannabinoid signaling through CB1 receptor to regulate bone metabolism has not been characterized. Here we demonstrate that gAPN downregulated CB1 expression in embryonic mouse hypothalamus N1 cells in vitro. gAPN intracerebroventricular (icv) infusions also decreased hypothalamic CB1 expression and bone formation parameters in APN-knockout (APN-KO) and wild-type mice. Most importantly, mice pretreated with icv infusions with the CB1 receptor agonist arachidonyl-2'-chloroethylamine or antagonist rimonabant attenuated or enhanced respectively central APN induction of bone formation. We then investigated whether epigenetic signaling mechanisms were involved in the downregulation of hypothalamic CB1 expression by gAPN. We found gAPN enhanced expression levels of various histone deacetylases (HDACs), especially HDAC5. Furthermore, chromatin immunoprecipitation assays revealed HDAC5 bound to the transcriptional start site transcription start site 2 region of the CB1 promoter. In summary, our study identified a possible novel central APN-HDAC5-CB1 signaling mechanism that promotes peripheral bone formation through epigenetic regulation of hypothalamic CB1 expression.
Assuntos
Adiponectina/administração & dosagem , Adiponectina/metabolismo , Remodelação Óssea/efeitos dos fármacos , Osso Esponjoso/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Receptor CB1 de Canabinoide/metabolismo , Adiponectina/deficiência , Adiponectina/genética , Animais , Sítios de Ligação , Osso Esponjoso/metabolismo , Células Cultivadas , Regulação para Baixo , Fêmur/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Hipotálamo/metabolismo , Infusões Intraventriculares , Camundongos Endogâmicos C57BL , Camundongos Knockout , Regiões Promotoras Genéticas , Receptor CB1 de Canabinoide/genéticaRESUMO
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 TratamentoRESUMO
Adiponectin (APN) has been shown to play a key role in regulating bone mineral density (BMD). Nevertheless, the effects of APN on receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation and mechanism of regulation are not entirely clear. The study, therefore, aimed to evaluate the effect of APN on osteoclastogenesis. Our results showed that APN inhibits osteoclastogenesis and resorption function in vitro by suppressing nuclear factor-κB (NF-κB) and p38 signaling pathways, which is essential for osteoclast formation. Moreover, APN blocked the formation of F-actin rings and attenuated osteoclast-mediated bone resorptive function. Therefore, we concluded that APN may provide a potential treatment for osteoclast-related diseases, such as osteoporosis.