Effects of metformin and adiponectin on endometrial cancer cells growth / 北京大学学报(医学版)

OBJECTIVE@#To determine the effect of metformin and adiponectin on the proliferation of EC cells and the relationship between metformin and adiponectin.@*METHODS@#The proliferation impact of different concentrations of metformin and adiponectin on two types of EC cells ishikawa (IK) and HEC-1B was confirmed by CCK-8 method. qRT-PCR and Western blot were used to detect the effect of different concentrations of metformin on the changes of adiponectin receptors (AdipoR1 and AdipoR2) of the EC cells both in mRNA and protein level and the role of compound C, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor, on the above effects.@*RESULTS@#(1) Both metformin and adiponectin could significantly promote the proliferation of endometrial cancer (EC) cells in a time and concentration dependent manner (P<0.05).(2)Metformin and adiponectin had synergy anti-proliferative effect on EC cells and the combination index (CI) value of IK cells was 0.906 34 and of HEC-1B cells was 0.827 65. (3)qRT-PCR was used to detect the mRNA levels of AdipoR1 and AdipoR2 after 5 mmol/L and 10 mmol/L metformin, respectively, stimulating IK and HEC-1B cells for 48 hours and the mRNA expressions of AdipoR1 and AdipoR2 were significantly increased when compared with the control group (0 mmol/L)(IK: AdipoR1 of 5 mmol/L and 10 mmol/L group: P<0.001,AdipoR2 of 5 mmol/L group: P<0.001; HEC-1B: AdipoR1 of 5 mmol/L group: P<0.001, 10 mmol/L group: P=0.023, AdipoR2 of 5 mmol/L group: P<0.001, 10 mmol/L group: P=0.024). When combined with compound C, the RNA levels of AdipoR1 and AdipoR2 were not different compared with the control group (0 mmol/L, P>0.05). (4) Western blot was used to detect the protein levels of AdipoR1 and AdipoR2 after 5 mmol/L and 10 mmol/L metformin, stimulating IK and HEC-1B cells for 48 hours and the protein level was significantly increased when compared with the control group (0 mmol/L)(IK: AdipoR1 of 5 mmol/L group: P=0.04, 10 mmol/L group: P=0.033, AdipoR2 of 5 mmol/L group: P=0.044, 10 mmol/L group: P=0.046; HEC-1B: AdipoR1 of 5 mmol/L group: P=0.04, 10 mmol/L group: P=0.049, AdipoR2 of 5 mmol/L group: P=0.043, 10 mmol/L group: P=0.035). When combined with compound C,the protein levels of AdipoR1 and AdipoR2 were not different compared with the control group (0 mmol/L, P>0.05).@*CONCLUSION@#We find that metformin and adiponectin have synergy anti-proliferative effect on EC cells. Besides, metformin can increase adiponectin receptors expressions of EC cells both in mRNA and protein levels and this effect is accomplished by the activation of AMPK signaling 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.

Relationship between adiponectin, obesity and insulin resistance / Relação entre adiponectina, obesidade e resistência à insulina

Objectives: the conditions of obesity and overweight pose a major risk for a number of comorbidities, including clinical syndromes resulting from atherosclerotic disease. Recent studies strongly indicate that adipose tissue is an active endocrine organ that secretes bioactive factors such as adipokines. Adiponectin appears to have a regulatory role in the mechanism of insulin resistance and in the development of atherosclerosis. This systematic review aims to evaluate the anti-atherogenic effects of adiponectin and its properties to improve and mimic metabolic and vascular actions of insulin and its influence on endothelial function. Methods: a qualitative, exploratory and literature review was performed in the PubMed, Portal Capes and Scielo databases using as key-words "adiponectin", "obesity", "insulin resistance", "anti-inflammatory", "therapeutic strategies" and "future prospects". Results: evidence suggests that adiponectin has anti-atherogenic properties with anti-inflammatory effects on the vascular wall. Moreover, it modifies the vascular intracellular signaling and has indirect antioxidant effects on the human myocardium. On the other hand, there are studies suggesting that increased levels of adiponectin are paradoxically associated with a worse prognosis in heart failure syndrome, although the mechanisms are not clear. Conclusion: it is not clear whether adiponectin levels have any clinical significance for risk stratification in cardiovascular disease or if they simply reflect the activation of complex underlying mechanisms. Changes in lifestyle and some drug treatments for hypertension and coronary heart disease have shown significant effect to increase adiponectin levels, and simultaneously decrease in insulin resistance and endothelial dysfunction. .

Objetivos: as condições de obesidade e sobrepeso representam um grande risco para uma série de comorbidades, incluindo as síndromes clínicas decorrentes da doença aterosclerótica. Recentes estudos indicam fortemente que o tecido adiposo é um órgão endócrino ativo que secreta fatores bioativos, como as adipocinas. A adiponectina parece ter um papel regulador no mecanismo da resistência à insulina e no desenvolvimento da aterosclerose. Este estudo de revisão tem como objetivo avaliar os efeitos antiaterogênicos da adiponectina e suas propriedades para melhorar e reproduzir ações metabólicas e vasculares de insulina e sua influência na função endotelial. Métodos: revisão qualitativa, exploratória e bibliográfica foi realizada nas bases de dados PubMed, Portal Capes e Scielo utilizando os unitermos "adiponectin", "obesity", "insulin resistance", "anti-inflammatory", "therapeutic strategies" e "future prospects". Resultados: evidências sugerem que a adiponectina tem propriedades antiaterogênicas com efeitos anti-inflamatórios sobre a parede vascular. Além disso, modifica a sinalização vascular intracelular e exerce efeitos antioxidantes indiretos sobre o miocárdio humano. Por outro lado, existem estudos que sugerem que níveis aumentados de adiponectina são paradoxalmente associados com pior prognóstico na síndrome de insuficiência cardíaca, embora os mecanismos ainda não estejam claros. Conclusão: é incerto se os níveis de adiponectina têm algum significado clínico para a estratificação de risco na doença cardiovascular ou se simplesmente refletem a ativação dos mecanismos complexos subjacentes. Modificações de estilo de vida e alguns tratamentos medicamentosos para hipertensão e doenças coronarianas têm tido efeitos importantes para aumentar os níveis de adiponectina e, simultaneamente, diminuir a resistência à insulina e a disfunção endotelial. .

Protective roles of adiponectin in obesity-related fatty liver diseases: mechanisms and therapeutic implications: [review] / Adiponectina e seu papel na proteção contra a doença hepática gordurosa na obesidade: mecanismos e implicações terapêuticas: [revisão]

Adiponectin is an insulin-sensitizing adipokine possessing multiple beneficial effects on obesity-related medical complications. This adipokine is secreted from adipocytes into the circulation as three oligomeric isoforms, including trimer, hexamer and the high molecular weight (HMW) oligomeric complex. Each oligomeric isoform of adiponectin possesses distinct biological properties and activates different signaling pathways in various target tissues. The hepato-protective activities have been demonstrated by many clinical and experimental studies. The decreased level of serum adiponectin represents an independent risk factor for nonalcoholic fatty liver disease (NAFLD) and liver dysfunctions in humans. In animals, elevation of circulating adiponectin by either pharmacological or genetic approaches leads to a significant alleviation of hepatomegaly, steatosis and necro-inflammation associated with various liver diseases. In adiponectin knockout mice, there is a pre-existing condition of hepatic steatosis and mitochondria dysfunction, which might contribute to the increased vulnerabilities of these mice to the secondary liver injuries induced by obesity and other conditions. This review aims to summarize recent advances on delination of the structural, molecular and cellular mechanisms underlying the hepato-protective properties of adiponectin.

A adiponectina é uma adipocitocina com ação insulino-sensibilizadora com múltiplos efeitos benéficos sobre as complicações clínicas da obesidade. Essa adipocitocina é secretada pelos adipócitos na circulação sistêmica em três isoformas oligoméricas, incluindo as formas em trímeros, hexâmeros e complexas de alto peso molecular (HMW). Cada forma oligomérica da adiponectina apresenta propriedades biológicas distintas e ativam diferentes vias de sinalização celular em diversos tecidos. Suas atividades hepatoprotetoras têm sido descritas em vários estudos clínicos e experimentais. Em humanos, os níveis reduzidos da adiponectina sérica, características da obesidade, representam um fator de risco independente para a doença hepática gordurosa não-alcoólica (NAFLD), incluindo variados graus de disfunções hepáticas. Em animais, a elevação dos níveis circulantes de adiponectina, por manipulações genéticas ou farmacológicas, conduz a uma atenuação da hepatomegalia, da esteatose e da necroinflamação usualmente associadas a várias doenças hepáticas. No animal sem o gene da adiponectina (knockout), existe uma condição preexistente de esteatose e disfunção mitocondrial que contribui para a vulnerabilidade desses animais aos processos de lesões teciduais hepáticos induzidos pela obesidade e outras condições. Esta revisão sumariza os recentes avanços na compreensão e caracterização dos mecanismos celulares, moleculares e estruturais das ações hepatoprotetoras da adiponectina.

Hypoadiponectinemia in obese and diabetic subjects in the State of Qatar

Obesity is commonly associated with insulin resistance [IR], and is a common cause of type 2 diabetes. Adiponectin is an adipose tissue protein that enhances insulin sensitivity and has anti-atherogenic properties This study was done to determine the adiponectin level and its relations to key components of the metabolic syndrome in obese diabetic [OD], obese non-diabetic [OB] and control [non-obese, non-diabetic [NOND]] Qatari subjects We examined 64 [OD], 61 [OB] and 72 [NOND] male and female subjects. After a 12 h overnight fasting, blood samples were withdrawn for determination of plasma glucose, insulin, adiponectin, HbA1C, uric acid, total cholesterol, triglycerides, HDL-C and LDL-C Plasma levels of adiponectin in OD [10.60 +/- 3.64microg/mL] and OB [11.21 +/- 3.41microg/mL] were significantly lower than NOND controls [14.73 +/- 4.97microg/mL]. Significant, inverse correlations were observed between adiponectin levels and BMI [r=-0.241, p < 0.05], plasma glucose [r=-0.221, p < 0.05], insulin [r=-0.280, p < 0.05], C-peptide [r=-0.334, P < 0.01], total cholesterol [r=-0.243, p < 0.01,], triglycerides [r=-0.438, p < 0.01], LDL-C [r=-0.214, p < 0.05] and uric acid [r=-0.286, p < 0.05]. In addition, correlated positively with HDL-C[r=0.386, p < 0.01]. In multiple regression analysis, only TG was inversely associated with plasma level of adiponectin in all groups. This study provides the first evidence that adiponectin is reduced in Qatari obese subjects with and without diabetes. The measurement of circulating adiponectin among Qatari obese subjects is suggested to monitor cardiovascular disease [CVD] risks. Whether the plasma adiponectin level could be a suitable biomarker for following the clinical progress of CVD among Qatari obese and diabetic subjects warrants further investigation

Adipocyte Signals in Energy Balance and Digestive Diseases / 대한소화기학회지

For the regulation of energy balance in various internal organs including gut, pancreas and liver, visceral adipose tissue and brain perform important sensing and signaling roles via neural and endocrine pathway. Among these, adipose tissue has been known as a simple energy-storing organ, which stores excess energy in triglyceride. However, it became apparent that adipocytes have various receptors related to energy homeostasis, and secrete adipocytokines by endocrine, paracrine and autocrine mechanisms. In this review, basic roles of adipocytes in energy homeostasis and the correlation between adipocyte signals and digestive diseases are discussed.