Cloning of adipor1 and adipor2 genes in Rana dybowskii and its expression pattern upon infection / 生物工程学报

Adiponectin receptor 1 (AdipoR1) and Adiponectin receptor 2 (AdipoR2) can bind to adiponectin (AdipoQ) secreted by adipose tissue to participate in various physiological functions of the body. In order to explore the role of AdipoR1 and AdipoR2 in amphibians infected by Aeromonas hydrophila (Ah), the genes adipor1 and adipor2 of Rana dybowskii were cloned by reverse transcription-polymerase chain reaction (RT-PCR) and analyzed by bioinformatics. The tissue expression difference of adipor1 and adipor2 was analyzed by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR), and an inflammatory model of R. dybowskii infected by Ah was constructed. The histopathological changes were observed by hematoxylin-eosin staining (HE staining); the expression profiles of adipor1 and adipor2 after infection were dynamically detected by qRT-PCR and Western blotting. The results show that AdipoR1 and AdipoR2 are cell membrane proteins with seven transmembrane domains. Phylogenetic tree also shows that AdipoR1 and AdipoR2 cluster with the amphibians in the same branch. qRT-PCR and Western blotting results show that adipor1 and adipor2 were up-regulated at different levels of transcription and translation upon Ah infection, but the response time and level were different. It is speculated that AdipoR1 and AdipoR2 participate in the process of bacterial immune response, providing a basis for further exploring the biological functions of AdipoR1 and AdipoR2 in amphibians.

Xiaoyao San, a Chinese herbal formula, ameliorates depression-like behavior in mice through the AdipoR1/AMPK/ACC pathway in hypothalamus / 中西医结合学报

OBJECTIVE@#Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.@*METHODS@#An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins.@*RESULTS@#XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.@*CONCLUSION@#Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.

The role of adiponectin in ischemia-reperfusion syndrome: a literature review / O papel da adiponectina na síndrome de isquemia e reperfusão: revisão de literatura

ABSTRACT Adiponectin, among other diverse adipokines, is produced in greater quantity and has an effect on the adipose tissue and other tissues in the body. Adiponectin plays three main roles: regulatory metabolic and sensitizing function of insulin in the liver and muscles; it acts as an anti-inflammatory cytokine and in vascular protection, besides important cardiac protection in the presence of ischemia-reperfusion syndrome. Since many situations resulting from traumatic accidents or pathologies are due to cell damage caused by ischemia-reperfusion syndrome, it is relevant to study new therapeutic alternatives that will contribute to reducing these lesions. The objective of this study is to carry out a literature review on the role of adiponectin in ischemia-reperfusion syndrome.

RESUMO A adiponectina, em meio a outras diversas adipocinas, é a produzida em maior quantidade e exerce efeitos no próprio tecido adiposo e em outros diversos tecidos do organismo. Dentre suas funções, a adiponectina apresenta três principais papéis: função metabólica regulatória e sensibilizadora da insulina no fígado e nos músculos atua como citocina anti-inflamatória e vasculoprotetora, além de exercer importante fator cardioprotetor na presença da síndrome de isquemia e reperfusão. Visto que inúmeras situações decorrentes de acidentes traumáticos ou patologias recaem no dano celular causado pela síndrome de isquemia e reperfusão, observa-se a importância de estudar novas alternativas terapêuticas que venham a contribuir para a diminuição dessas lesões. O objetivo do presente estudo é realizar uma revisão de literatura sobre o papel da adiponectina na síndrome de isquemia e reperfusão.

Pancreatic ß-cell function is inhibited by miR-3666 in type 2 diabetes mellitus by targeting adiponectin

Type 2 diabetes mellitus (T2D) is a common endocrine and metabolic disorder, and poses threats to human health worldwide. Recently, microRNAs (miRNAs) have been suggested to play important roles in the pathophysiology of T2D. In this study, we explored the role of miR-3666 in T2D. miR-3666 was significantly down-regulated in the serum of T2D patients when compared to that of healthy volunteers, and miR-3666 expression level was negatively correlated with blood glucose levels of T2D patients. Overexpression of miR-3666 inhibited cell proliferation, reduced insulin secretion, and promoted cell apoptosis of pancreatic β-cell line (INS-1 cells). On the other hand, knockdown of miR-3666 had the opposite effects in INS-1 cells. The bio-informatics analysis using TargetScan revealed that adiponectin (ADIPOQ) was a downstream target of miR-3666, and the interaction between miR-3666 and ADIPOQ was validated by luciferase reporter assay. In addition, miR-3666 negatively regulated the mRNA and protein expression of ADIPOQ. Overexpression of ADIPOQ promoted insulin secretion after glucose stimulation, promoted cell proliferation, inhibited cell apoptosis, and partially abolished the effects of miR-3666 overexpression on insulin secretion, cell proliferation, and cell apoptosis of INS-1 cells. In conclusion, our results revealed that miR-3666 inhibited pancreatic cell proliferation, reduced insulin sensitivity, and promoted apoptosis by targeting ADIPOQ.

Adiponectin levels and sleep deprivation in patients with endocrine metabolic disorders

SUMMARY BACKGROUND: Sleep abnormalities are frequent in patients with endocrine metabolic disorders (EMD) such as arterial hypertension, diabetes and obesity. Adiponectin is a peptide largely secreted by adipocytes and has various properties e.g. anti-inflammatory, antioxidant, antiatherogenic, pro-angiogenic, vasoprotective and insulin-sensitizing. Adiponectin inversely relates to body weight and when its concentration decreases, the resistin concentration increases resulting in greater insulin resistance. OBJECTIVE: The objective of this study is to examine factors influencing adiponectin levels in a population with EMD. METHODS: This was a cross-sectional evaluation of 332 patients (18 to 80y) presenting arterial hypertension, pre-diabetes, diabetes, and/or obesity. Investigation included clinical evaluation of comorbidities, general blood tests and adiponectin measures (ELISA). Chronic sleep deprivation was determined if habitual sleep was <6 hours >4 days/week. RESULTS: Arterial hypertension (78.5%), type-2 diabetes (82.3%), and overweight (45.0%)/obesity (38.8%) were frequent. Patients with type-2 diabetes tended to have more chronic sleep deprivation (p=0.05). Adiponectin levels increased with age and were inversely correlated with sagittal abdominal diameter (p=0.04) and fasting insulin (p=0.001). Chronic sleep deprivation was associated with higher adiponectin concentration [OR=1.34; CI=1.13-1.58; p<0.005] and this was maintained after adjustment for gender, age, body mass index, menopause, arterial hypertension, American Diabetes Association classification and physical exercise levels [OR=1.38; 0=1.14-1.66: p=0.001]. CONCLUSION: In patients with EMD, adiponectin is influenced not only by obesity but also by age and sleep deprivation. The latter finding may be explained by a compensatory effect or a counter regulation to minimize the harmful effects of sleep deprivation.

RESUMO INTRODUÇÃO: Problemas de sono são frequentes em pacientes com distúrbios endócrino-metabólicos (DEM), como hipertensão arterial, diabetes e obesidade. A adiponectina é um peptídeo segregado por adipócitos e apresenta diversas propriedades, como por exemplo, anti-inflamatória, antioxidante, antiaterogênica, pró-angiogênica e vasoprotetora. A adiponectina relaciona-se inversamente com o peso corporal. OBJETIVO: Examinar os fatores que influenciam os níveis de adiponectina em uma população com DEM. MÉTODOS: Trata-se de uma avaliação transversal com 332 pacientes (18 a 80 anos) apresentando hipertensão arterial, pré-diabetes, diabetes e/ou obesidade. A investigação incluiu avaliação clínica de comorbidades, exames de sangue e medidas de adiponectina (Elisa). A restrição crônica do sono foi determinada com o sono habitual <6 horas >4 dias/semana. RESULTADOS: Doenças como hipertensão arterial (78,5%), diabetes tipo 2 (82,3%) e sobrepeso (45,0%)/obesidade (38,8%) foram frequentes. Pacientes com diabetes tipo 2 apresentaram uma tendência na restrição crônica do sono (p=0,05). Os níveis de adiponectina aumentaram com a idade e foram inversamente correlacionados com o diâmetro abdominal sagital (p=0,04) e com a insulina em jejum (p=0,001). A restrição crônica do sono foi associada à maior concentração de adiponectina [OR=1,34; CI=1,13-1,58; p<0,005] e isso foi mantido após ajuste por gênero, idade, índice de massa corporal, menopausa, hipertensão arterial, classificação dos níveis da American Diabetes Association e exercício físico [OR=1,38; CI=1,14-1,66: p=0,001]. CONCLUSÕES: Em pacientes com DEM, a adiponectina é influenciada não apenas pela obesidade, mas também pela idade e pela restrição de sono. O último achado pode ser explicado por um efeito compensatório ou por um regulamento contrário para minimizar os efeitos nocivos da restrição do sono.

Relationships between adiponectin levels, the metabolic syndrome, and type 2 diabetes: a literature review

ABSTRACT Elevated hepatic glucose production, impaired insulin secretion, and insulin resistance - abnormalities of glucose metabolism typically found in subjects with obesity - are major factors underlying the pathogenesis of type 2 diabetes (DM2) and the metabolic syndrome (MS). Adiponectin is a major regulator of glucose and lipid homeostasis via its insulin-sensitizing properties, and lower levels seems to be associated with the development of DM2 and MS. The purpose of this review is to clarify the mechanisms whereby adiponectin relates to the development of DM2 and MS and the association between polymorphisms of the adiponectin gene, circulating levels of the hormone, and its relationships with DM2. In addition, the impact of dietary lipids in the circulating levels of adiponectin will be addressed. According to the literature, circulating adiponectin levels seem to decrease as the number of MS components increases. Lower adiponectin concentrations are associated with higher intra-abdominal fat content. Therefore, adiponectin could link intra-abdominal fat with insulin resistance and development of MS. Therapeutic strategies that target the MS and its components, such as lifestyle modification through physical activity and weight loss, have been shown to increase adiponectin concentrations. Possible roles of diets containing either low or high amounts of fat, or different types of fat, have been analyzed in several studies, with heterogeneous results. Supplementation with n-3 PUFA modestly increases adiponectin levels, whereas conjugated linoleic acid supplementation appears to reduce concentrations when compared with unsaturated fatty acid supplementation used as an active placebo.

Adiponectin inhibits oxidization-induced differentiation of T helper cells through inhibiting costimulatory CD40 and CD80

Adiponectin is a multifunctional adipokine that has several oligomeric forms in the blood stream, which broadly regulates innate and acquired immunity. Therefore, in this study, we aimed to observe the differentiation of T helper (Th) cells and expression of costimulatory signaling molecules affected by adiponectin. The mRNA and protein expression levels of adiponectin and its receptors in oxidized low density lipoprotein cholesterol-treated endothelial cells were assayed by real time PCR and immunofluorescence. The endothelial cells were then treated with adiponectin with or without adipoR1 or adipoR2 siRNA and co-cultured with T lymphocytes. The distribution of Th1, Th2 and Th17 subsets were assayed by flow cytometry. The effects of adiponectin on costimulatory signaling molecules HLA-DR, CD80, CD86 and CD 40 was also assayed by flow cytometry. The results showed that endothelial cells expressed adiponectin and its receptor adipoR1 and adipoR2, but not T-cadherin. Adiponectin suppressed Th1 and Th17 differentiation through adipoR1 receptor, contributed to the inhibition of CD80 and CD40, and inhibited differentiation of Th1 and Th17 by inhibiting antigen presenting action.

Resistance exercise improves metabolic parameters and changes adipocyte-derived leptin: a comparison between genders in untrained adults

This study examined gender differences after resistance exercise (RE) by measuring fasting plasma levels of creatine kinase, lipid profile, blood glucose, adiponectin, tumor necrosis factor alpha (TNF-α), and leptin. Thirteen women (23.6 ± 7.3 years) and 11 men (29.5 ± 9 years) were enrolled in the study. Two bouts of RE were performed on two different occasions separated by 48 h each. Blood samples were collected and analyzed at baseline and 15 h after the last RE session. Increased creatine kinase levels and improvements in lipid profile and blood glucose were found for both genders. No changes in adiponectin and TNF-α levels were observed for both genders, but leptin levels were reduced (p < 0.05) only for women after RE. Collectively, our findings clearly show that RE was effective in lowering blood glucose and that this effect was not accompanied by changes in adiponectin levels in healthy subjects, indicating that RE is still an important tool for the prevention of metabolic diseases. Furthermore, two sessions of RE promoted a reduction in leptin levels in women, even though no changes in body weight were found, showing that RE is an interesting approach to study obese patients and metabolic regulation

Platelet Rich Plasma (PRP) Produces an Atherofibrotic Histophenotype During Craniofacial Bone Repair Due to Changes of Immunohistochemical Expression of Erk1/2, p38α /β, Adiponectin and Elevated Presence of Cells Exhibiting B-scavenger Receptor (CD36+)

Abstract The platelet-extracellular matrix interaction in platelet rich plasma (PRP) through thrombospondin receptor-CD36 induces the secretion of growth factors responsible for cellular proliferation and differentiation during the repair process. Since CD36 also acts as a class B-scavenger-receptor for development of foam-like cells and mitogen-activated kinases, such as Erk1/2 and p38α/β, are important proteins activated by platelet growth factor, the aim of this study was to evaluate the immunohistochemical presence of CD36, Erk1/2, p38α/β during the bone repair treated and non-treated with PRP and to compare these results with the histomorphometry of repair. Simultaneously, the immunopresence of adiponectin was analyzed, which may contribute to osteogenesis at the same time it inhibits fibrosis and impairs adipogenesis and foam cell formation in the medullary area. An artificial bone defect measuring 5×1 mm was produced in the calvaria of 56 Wistar rats. The defects were randomly treated with autograft, autograft+PRP, PRP alone and sham. The animals were euthanized at 2 and 6 weeks post-surgery. Data were analyzed by ANOVA followed by non-parametric test Student Newman-Keuls (p<0.05) for histomorphometric and immunohistochemical interpretation. The results revealed that in specimens that received PRP the immunopositivity for Erk1/2, p38α/β and CD36 proteins increased significantly while the immunohistochemical expression of adiponectin decreased simultaneously. There was also an accentuated reduction of bone matrix deposition and increase of the medullary area represented by fibrosis and/or presence of foam-like cells, which exhibited immunophenotype CD36+adiponectin. The findings of this study suggest that PRP acted as an inhibitor of osteogenesis during the craniofacial bone repair and induced a pathological condition that mimics an atherofibrotic condition.

Resumo A interação da matriz extracelular-plaquetas no plasma rico em plaquetas (PRP) através de receptor trombospondina CD36 induz a secreção de fatores de crescimento responsáveis pela proliferação e diferenciação celular durante o processo de reparo. Uma vez que o CD36 também age como receptor scavenger de classe B para o desenvolvimento de células do tipo espuma, e as quinases ativadas por mitógenos, tais como ERK1/2 e p38α/β, são importantes proteínas ativadas por fator de crescimento das plaquetas, o objetivo deste estudo foi avaliar a presença imunoistoquímica de CD36, ERK1/2, p38α/β durante o reparo ósseo tratado e não-tratado com PRP e comparar estes resultados com a histomorfometria do reparo. Simultaneamente, analisou-se a imunopresença da adiponectina, que pode contribuir para osteogênese ao mesmo tempo que inibe a fibrose e prejudica a formação de células tipo espuma/xantomatosas na área medular. Um defeito artificial de osso medindo 5×1 mm foi produzido na calvária de 56 ratos Wistar. Os defeitos foram tratados aleatoriamente com auto-enxerto, enxerto autógeno+PRP, PRP apenas e sham. Os animais foram sacrificados 2 e 6 semanas pós-cirurgia. Os dados foram examinados por meio de ANOVA, seguido pelo teste não-paramétrico Student Newman-Keuls (p<0,05) para a interpretação histomorfométrica e imunoistoquímica. Os resultados revelaram que as amostras que receberam PRP aumentaram significativamente a imunopositividade para as proteínas ERK1/2, p38α/β e CD36, simultaneamente à diminuição de expressão imunoistoquímica da adiponectina. Houve também expressiva redução de deposição de matriz óssea e aumento da área medular representada por fibrose e/ou presença de células do tipo espuma que apresentaram imunofenótipo CD36 + adiponectina. Estes resultados sugerem que o PRP atuou como um inibidor da osteogênese durante o reparo ósseo craniofacial e induziu uma condição patológica que mimetiza uma condição aterofibrótica.

Potential role of marine algae extract on 3T3-L1 cell proliferation and differentiation: an in vitro approach

BACKGROUND: From ancient times, marine algae have emerged as alternative medicine and foods, contains the rich source of natural products like proteins, vitamins, and secondary metabolites, especially Chlorella vulgaris (C. vulgaris) contains numerous anti-inflammatory, antioxidants and wound healing substances. Type 2 diabetes mellitus is closely associated with adipogenesis and their factors. Hence, we aimed to investigate the chemical constituents and adipo-genic modulatory properties of C. vulgaris in 3T3-L1 pre-adipocytes. RESULTS: We analysed chemical constituents in ethanolic extract of C. vulgaris (EECV) by LC-MS. Results revealed that the EECV contains few triterpenoids and saponin compounds. Further, the effect of EECV on lipid accumulation along with genes and proteins expressions which are associated with adipogenesis and lipogenesis were evaluated using oil red O staining, qPCR and western blot techniques. The data indicated that that EECV treatment increased differentiation and lipid accumulation in 3T3-L1 cells, which indicates positive regulation of adipogenic and lipogenic activity. These increases were associated with up-regulation of PPAR-γ2, C/EBP-α, adiponectin, FAS, and leptin mRNA and protein expressions. Also, EECV treatments increased the concentration of glycerol releases as compared with control cells. Troglitazone is a PPAR-γ agonist that stimulates the PPAR-y2, adiponectin, and GLUT-4 expressions. Similarly, EECV treatments significantly upregulated PPAR-γ, adiponectin, GLUT-4 expressions and glucose utilization. Further, EECV treatment decreased AMPK-α expression as compared with control and metformin treated cells. CONCLUSION: The present research findings confirmed that the EECV effectively modulates the lipid accumulation and differentiation in 3T3-L1 cells through AMPK-α mediated signalling pathway.

Adiponectina: caracterização, ação metabólica e cardiovascular / Adiponectin: characterization, metabolic and cardiovascular action

Nas últimas duas décadas, o entendimento da biologia do tecido adiposo sofreu mudanças revolucionárias, passando de principal sítio de armazenamento energético a importante órgão endócrino responsável pela produçãoe secreção de proteínas, peptídeos e não peptídeos bioativos. Dentre as proteínas secretadas pelos adipócitos, aadiponectina (APN) é a mais abundante, apresentando ações fisiológicas importantes no sistema cardiovasculare endócrino, envolvendo a sensibilização da ação insulínica e regulação do metabolismo energético corporal, incluindo o coração. Esta revisão tem por objetivo descrever a ação da APN sobre o sistema cardiovascular. Foramincluídos artigos originais realizados com animais ou humanos. Consultadas as bases de dados Pubmed e Medlineentre os anos de 1994 e 2013. Não foram incluídos relatos de caso, estudos-piloto ou estudos de revisão. Utilizou-se como palavras-chave os descritores em ciências da saúde e MeSH específico para o Medline. Oscruzamentos realizados foram: Adiponectin AND Obesity, Adiponectin AND Metabolism e Adiponectin AND Cardiovascular Disease. Encontrados 303 artigos, excluídos 204 e selecionados 31 artigos que compuseram esteestudo. No contexto geral desta revisão a APN apresenta efeitos anti-inflamatórios e ateroprotetores no tecidovascular e ainda ação sensibilizadora para a insulina nos tecidos envolvidos nos metabolismos glicídico e lipídico. Assim, é considerado biomarcador importante para o desenvolvimento de doenças cardiovasculares.

In the last two decades, the understanding of adipose tissue biology underwent revolutionary changes, from a major energy storage site to an important endocrine organ responsible for the production and secretion of proteins, peptides and non-bioactive peptides. Among the proteins secreted by adipocytes, adiponectin (APN) is the most abundant, with important physiological actions in the cardiovascular and endocrine system, involving the sensitization of insulin action and regulation of body energy metabolism, including the heart. This review aims to describe the action of APN on the cardiovascular system. It includes original manuscripts with humans or animals. The databases PubMed and Medline, from years 1994 to 2013, were searched. Case reports, pilot studies or review studies have not been included. The health science descriptors and MeSH specific for Medline were used as keywords. The following cross searches were carried out: Adiponectin AND Obesity, Adiponectin AND Metabolism and Adiponectin AND Cardiovascular Disease. We found 303 manuscripts, excluded 204 and selected 31 manuscripts that were included this study. Inthe general context of this review, APN presents anti-inflammatory and ateroprotector effects in the vascular tissue and an insulin sensitizing action in tissues involved in glucose and lipid metabolism. It is thus considered an important biomarker for the developmentof cardiovascular diseases.

Arterial blood and end-tidal concentrations of sevoflurane during the emergence from anesthesia in gynecologic patients

OBJECTIVE: The end-tidal concentration of inhalation anesthetics is a clinical indicator for predicting the emergence from anesthesia. This study was conducted to assess the relationship between arterial blood and end-tidal sevoflurane concentrations during emergence. METHODS: Thirty-two female American Society of Anesthesiologists physical status I-II patients receiving general anesthesia for elective gynecologic surgery were included. A fixed dose of 3.5% inspiratory sevoflurane in 6 L min-1 oxygen was maintained until the end of surgery. At 20 and 10 minutes before and 0, 5, 10, 15, and 20 minutes after discontinuing sevoflurane, as well as at the time of eye opening by verbal command, defined as awakening, 1 ml arterial blood was obtained to measure its sevoflurane concentration by gas chromatography. Simultaneous inspiratory and end-tidal concentrations of sevoflurane were detected by an infrared analyzer and tested by Bland-Altman agreement analysis. RESULTS: The arterial blood concentrations of sevoflurane were similar to the simultaneous end-tidal concentrations during emergence: 0.36% (0.10) and 0.36% (0.08) sevoflurane at awakening, respectively. The mean time from discontinuing sevoflurane to eye opening was 15.8 minutes (SD 2.9, range 10-26) and was significantly correlated with the duration of anesthesia (52-192 minutes) (P = 0.006) but not with the body mass index or total fentanyl dose. CONCLUSION: The mean awakening arterial blood concentration of sevoflurane was 0.36%. The time to awakening was prolonged in accordance with the anesthetic duration within 3 hours. With well-assisted ventilation during emergence, the sevoflurane end-tidal concentration was nearly equal to its arterial blood concentration, which could be a feasible predictor for awakening. .

Adiponectin effect on nitric oxide secretion by normal and endometriotic human endometrial stromal cells: in vitro study / Efecto de la adiponectica sobre la secreción de óxido nítrico por células estromales de endometrio humano, normales y con endometriosis: estudio in vitro

Endometriosis is an estrogen-dependent disease in reproductive age women. Adiponectin and Nitric oxide (NO) have an important role in physiologic functions especially in human reproductive system. Levels of NO increased in the endometriosis patients but serum adiponectin levels decreased in woman with endometriosis. The aim of this study was to determine adiponectin effect on nitric oxide secretion by cultured normal and endometriotic human endometrial stromal cells. In this experimental study, normal (n= 10) and endometriotic endometrial biopsies (n= 10) were taken in sterile condition. Stromal cells isolated and cultured in in DMEM/ F12 medium and treated with adiponectin concentrations (0, 10, 100, and 200 ng/ml) for 24 and 48 hours. NO assay was done on their supernatants by Greiss method. Data was analyzed by one way ANOVA and p<0.05 was considered significant. There was significant difference between endometriosis groups in NO secretion in all dose of adiponectin and time (p<0.05). In normal groups there was significant difference in 48 hours (p<0.05) but no significant change in 24 hours (p>0.05). Adiponectin effects nitric oxide secretion of cultured human endometriotic stromal cells.

La endometriosis es una enfermedad dependiente de estrógenos que se presenta en mujeres en edad reproductiva. La adiponectina y el óxido nítrico (ON) tienen un papel importante en las funciones fisiológicas, especialmente en el sistema reproductivo humano. Los niveles de ON aumentan en los pacientes con endometriosis, pero los niveles de adiponectina en suero disminuyen. El objetivo fue determinar el efecto de la adiponectina sobre la secreción de ON por las células estromales de endometrio humano, tanto normales como con endometriosis, en medio de cultivo. En este estudio experimental, las células estromales de endometrio normales (n= 10) y las biopsias de endometrio con endometriosis (n= 10) se tomaron en condiciones de esterilidad. Las células estromales fueron aisladas y cultivadas en un medio DMEM/F12, y se sometieron a distintas concentraciones de adiponectina (0, 10, 100, y 200 ng/ml) durante 24 y 48 horas. El ensayo con ON se realizó a los sobrenadantes obtenidos por el método de Greiss. Los datos recolectados fueron analizados por ANOVA de una vía y un valor p<0,05 se consideró significativo. Entre los grupos con endometriosis, en referencia a la secreción de ON, no hubo diferencia significativa en todas las dosis de adiponectina y los tiempos estipulados (p<0,05). En los grupos normales, hubo diferencia significativa a las 48 horas (p<0,05), pero ningún cambio significativo a las 24 horas (p>0,05). La adiponectina tiene efectos sobre la secreción de óxido nítrico por las células estromales endometriales humanas en cultivo.

Adiponectina modifica a resposta à suplementação de ômega-3 em humanos com fatores de risco cardiovascular / Adiponectin modifies the response to omega-3 suplementation in persons with cardiovascular risk factors

Ácidos graxos ômega-3 (-3) apresentam características cardioprotetoras e seu baixo consumo tem sido associado ao aumento da resistência insulínica e à baixa concentração de adiponectina no sangue. OBJETIVO: Testar se a suplementação com -3 melhora o perfil cardiometabólico em humanos com fator de risco cardiovascular e se a concentração basal de adiponectina modifica a resposta a essa suplementação. MÉTODOS: Neste ensaio clínico, duplo-cego, placebo-controlado e paralelo, distribuímos aleatoriamente 80 indivíduos nos grupos -3 (suplementado com 3,0 g/dia de óleo de peixe, contendo 37 por cento de ácido eicosapentaenoico [EPA] e 23 por cento de ácido docosahexaenoico [DHA]) e placebo (3,0 g/dia de óleo de girassol, contendo 65 por cento de ácido linoleico), ambos suplementados durante dois meses. Avaliamos concentração sérica de adiponectina e leptina, perfil lipídico e de apolipoproteínas, LDL eletronegativa, marcadores inflamatórios (interleucinas 2, 4, 6, 8 e 10, MCP1, IFN- e TNF-) e metabolismo glicídico (glicose e insulina), adotando nível de significância de 5 por cento . RESULTADOS: No momento basal, os grupos -3 e placebo foram semelhantes quanto ao sexo, idade (média de 52,0 anos), raça, estado civil, trabalho, escolaridade e renda. Após intervenção, o grupo -3 aumentou a concentração sérica de adiponectina. No geral, as citocinas apresentaram redução após intervenção em ambos os grupos; IL-10 foi a única cuja concentração média aumentou, no grupo -3, mas, sem diferença significativa entre os grupos. Ao estratificar os indivíduos do grupo -3 segundo concentração basal de adiponectina, aqueles com menores concentrações tiveram maior redução de colesterol total, LDL, LDL/HDL, LDL/Apo B e LDL(-). Indivíduos que apresentaram maior variação da concentração de adiponectina reduziram a glicemia...

Omega-3 fatty acids (-3) have shown cardioprotective characteristics and their low consumption has been associated with increased insulin resistance and low blood concentration of adiponectin. OBJECTIVE: To analyze if -3 supplementation improves cardiometabolic profile in humans with cardiovascular risk factor and if adiponectin concentration at baseline level modifies the response to this supplementation. METHODS: In this double-blind, placebo-controlled, clinical trial, we randomized 80 subjects into two groups: -3 (supplemented with 3.0g/day of fish oil containing 37 per cent eicosapentaenoic acid [EPA] and 23 per cent docosahexaenoic acid [DHA]) and placebo (3.0g/day of sunflower oil containing 65 per cent linoleic acid). Both groups received supplementation for two months. At baseline period and after eight weeks of intervention, we evaluated serum adiponectin and leptin, lipid profile and apolipoproteins, electronegative LDL, inflammatory markers (interleukin 2, 4, 6, 8 and 10, MCP1, IFN- and TNF-) and glucose metabolism (glucose and insulin)...

New-onset Diabetes as an Early Sign of Pancreatic Cancer / 대한소화기학회지

While long-standing diabetes is a risk factor of pancreatic cancer, new-onset diabetes could be a consequence of underlying pancreatic malignancy. About 30% to 50% of pancreatic cancer patients have new-onset diabetes. Because diabetes develops in preclinical or early stages of pancreatic cancer, it could serve as an excellent clue for early detection of pancreatic cancer. Insulin resistance associated with hyperglycemia and hyperinsulinemia by diabetogenic factors secreted from cancer cells have been suggested to be a possible mechanism of pancreatic cancer-induced diabetes. It is difficult to differentiate pancreatic cancer-induced diabetes from the more common type 2 diabetes. Although several clinical features and potential biomarkers have been investigated, optimal strategies and modalities to screen pancreatic cancer among the new-onset diabetes have not yet been fully determined.

Reduced Food Intake is the Major Contributor to the Protective Effect of Rimonabant on Islet in Established Obesity-Associated Type 2 Diabetes

PURPOSE: Although the presence of cannabinoid type 1 (CB1) receptor in islets has been reported, the major contributor to the protective effect of rimonabant on islet morphology is unknown. We determined whether the protective effect of rimonabant on pancreatic islet morphology is valid in established diabetes and also whether any effect was independent of decreased food intake. MATERIALS AND METHODS: After diabetes was confirmed, Otsuka Long-Evans Tokushima Fatty rats, aged 32 weeks, were treated with rimonabant (30 mg/kg/d, rimonabant group) for 6 weeks. Metabolic profiles and islet morphology of rats treated with rimonabant were compared with those of controls without treatment (control group), a pair-fed control group, and rats treated with rosiglitazone (4 mg/kg/d, rosiglitazone group). RESULTS: Compared to the control group, rats treated with rimonabant exhibited reduced glycated albumin levels (p<0.001), islet fibrosis (p<0.01), and improved glucose tolerance (p<0.05), with no differences from the pair-fed control group. The retroperitoneal adipose tissue mass was lower in the rimonabant group than those of the pair-fed control and rosiglitazone groups (p<0.05). Rimonabant, pair-fed control, and rosiglitazone groups showed decreased insulin resistance and increased adiponectin, with no differences between the rimonabant and pair-fed control groups. CONCLUSION: Rimonabant had a protective effect on islet morphology in vivo even in established diabetes. However, the protective effect was also reproduced by pair-feeding. Thus, the results of this study did not support the significance of islet CB1 receptors in islet protection with rimonabant in established obesity-associated type 2 diabetes.

A link between sleep loss, glucose metabolism and adipokines

The present review evaluates the role of sleep and its alteration in triggering problems of glucose metabolism and the possible involvement of adipokines in this process. A reduction in the amount of time spent sleeping has become an endemic condition in modern society, and a search of the current literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and type 2 diabetes mellitus. The mechanism involved may be associated with the decreased efficacy of regulation of the hypothalamus-pituitary-adrenal axis by negative feedback mechanisms in sleep-deprivation conditions. In addition, changes in the circadian pattern of growth hormone (GH) secretion might also contribute to the alterations in glucose regulation observed during sleep loss. On the other hand, sleep deprivation stress affects adipokines - increasing tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and decreasing leptin and adiponectin -, thus establishing a possible association between sleep-debt, adipokines and glucose metabolism. Thus, a modified release of adipokines resulting from sleep deprivation could lead to a chronic sub-inflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes mellitus. Further studies are necessary to investigate the role of sleep loss in adipokine release and its relationship with glucose metabolism.

Expressão gênica de adiponectina no tecido adiposo epicárdico após intervenção coronária percutânea com implante de stent metálico / Adiponectin expression in epicardial adipose tissue after percutaneous coronary intervention with bare-metal stent

INTRODUÇÃO: A visão clássica de tecido adiposo como um reservatório passivo para o armazenamento de energia não é mais válido. Na última década, o tecido adiposo tem demonstrado funções endócrinas, sendo o peptídeo mais abundante secretado pelos adipócitos a adiponectina. O tecido adiposo epicárdico (TAE) é distribuído em torno das artérias coronárias e, a lesão endovascular causada pela presença de stent metálico intracoronário, poderia promover alterações inflamatórias na gordura periadventicial, contribuindo para reestenose. OBJETIVO: Determinar a expressão gênica de mediadores inflamatórios no tecido adiposo epicárdico após implante de stent metálico com reestenose que haviam sido encaminhados para tratamento cirúrgico. MÉTODOS: Amostras pareadas de TAE foram colhidas no momento da cirurgia de revascularização miocárdica (CRM) em 11 pacientes (n = 22), uma amostra foi obtida do tecido em torno da area com stent e outra amostra em torno da artéria coronária sem stent. Expressão local de adiponectina foi determinada por reação em cadeia de polymerase em tempo real utilizando Taq DNA polimerase. RESULTADOS: Em duas amostras, não houve expressão do gene da adiponectina. Fomos capazes de identificar adiponectina em 20 amostras, no entanto, o padrão de expressão gênica foi heterogêneo. Não percebemos especificidade quando comparamos TAE obtido próximo à área de stent ou distante da área de stent. CONCLUSÃO: Não houve correlação entre a expressão do gene de adiponectina e a presença de stent intracoronário.

BACKGROUND: The classical view of adipose tissue as a passive reservoir for energy storage is no longer valid. In the past decade, adipose tissue has been shown to have endocrine functions and the most abundant peptide secreted by adipocytes is adiponectin. Pericardial adipose tissue (PAT) is distributed around coronary arteries and endovascular injury, caused by the presence of intracoronary bare-metal stent (BMS), could promote inflammatory changes in the periadvential fat, contributing to vascular restenosis. OBJECTIVE: We sought to determine gene expression of inflammatory mediator in pericardial adipose tissue after bare-metal stent implantation and vascular restenosis that had been referred to operative treatment. METHODS: Paired samples of PAT were harvested at the time of elective coronary artery bypass surgery (CABG) in 11 patients (n=22), one sample was obtained of the tissue around BMS area and another sample around coronary artery without stent. Local expression of adiponectin was determined by real-time polymerase chain reaction (RT-PCR) using Taq DNA polymerase. RESULTS: In two samples, there was no gene expression of adiponectin. We are able to identify adiponectin in 20 samples, however, the pattern of gene expression were heterogeneous.We did not notice specificity when we compared PAT obtained near BMS area or far from BMS area. CONCLUSION: There were no correlation between adiponectin gene expression and presence of BMS.

Papel de la sensibilidad a la sal y los polimorfismos genéticos como determinantes de la modificación de los factores de riesgo cardiovascular durante la pérdida de peso en sujetos con sobrepeso u obesidad / Role of salt sensitivity and genetic polymorphisms as determinants of the modification of cardiovascular risk factors during weight loss in overweight or obese subjects

El incremento de la ingesta de sal no siempre se acompaña de un aumento en la presión arterial; aquellos sujetos que así lo hacen, son denominados Sal Sensibles (SS), mientras que los que no, se denominan Sal Resistentes (SR). La sensibilidad a la sal se ha asociado con mayor riesgo cardiometabólico y es más frecuente en los sujetos obesos hipertensos, sin embargo, no todos los obesos son SS y se desconoce como se origina este fenotipo. Debido a que la obesidad es un estado proinflamatorio, se propone que es necesario cierto grado y/o tiempo de obesidad para ser SS. Es por ello, que en esta investigación se evaluó el cambio en el tiempo de las interleuquinas 6, 10 y 18 (IL-6, IL-10 e IL-18), adiponectina, leptina, glicemia, lípidos, insulina, depuración de creatinina, microalbuminuria, ADMA, metabolitos urinarios del óxido nrico (NO), y además se estudió la prevalencia de los polimorfismos genéticos más frecuentemente asociados a riesgo cardiometabólico de la IL-6, 10,18, y de la sintasa de NO endotelial (eNOS), en sujetos SR (n=11) y SS (n=17), con sobrepeso u obesidad grado I, que fueron sometidos por 18 semanas a dieta y ejercicio. Se encontró que la pérdida de peso revertió el estado SS, el cual fue mas evidente en los sujetos que tenían más tiempo de obesidad, mayor concentración de insulina y ADMA sanguíneo, menor excreción urinaria de los metabolito del NO, mayor índice IL-6/ circunferencia abdominal y presentaban al alelo ä"del polimorfismo 4ab de la eNOS, por lo que se concluye que la sensibilidad a la sal pudiera ser producto de la interacción entre los componentes inflamatorios, vasculares y metabólicos y probablemente sea modulada por el polimorfismo 4ab de la eNOS