Adiponectin Ameliorated Pancreatic Islet Injury Induced by Chronic Intermittent Hypoxia through Inhibiting the Imbalance in Mitochondrial Fusion and Division / 中国医学科学杂志(英文版)

Objective This study aimed to assess the protective value of adiponectin (APN) in pancreatic islet injury induced by chronic intermittent hypoxia (CIH). Methods Sixty rats were randomly divided into three groups: normal control (NC) group, CIH group, and CIH with APN supplement (CIH+APN) group. After 5 weeks of CIH exposure, we conducted oral glucose tolerance tests (OGTT) and insulin released test (IRT), examined and compared the adenosine triphosphate (ATP) levels, mitochondrial membrane potential (MMP) levels, reactive oxygen species (ROS) levels, enzymes gene expression levels of

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 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.

Triiodothyronine modulates the expression of leptin and adiponectin in 3T3-L1 adipocytes / Triiodotironina modula a expressão de leptina e adiponectina em adipócitos 3T3-L1

Objective To study the effect of different doses of triiodothyronine on gene expression of the adipokines leptin and adiponectin, at different times, and to evaluate the difference in expression between the two adipokines in each group. Methods 3T3-L1 adipocytes were incubated with triiodothyronine at physiological dose (10nM) and supraphysiological doses (100nM or 1,000nM), or without triiodothyronine (control, C) for 0.5, 6, or 24 hours. Leptin and adiponectin mRNA was detected using real-time polymerase chain reaction (RT-PCR). One-way analyses of variance, Tukey’s test or Student’s t test, were used to analyze data, and significance level was set at 5%. Results Leptin levels decreased in the 1,000nM-dose group after 0.5 hour. Adiponectin levels dropped in the 10nM-dose group, but increased at the 100nM dose. After 6 hours, both genes were suppressed in all hormone concentrations. After 24 hours, leptin levels increased at 10, 100 and 1,000nM groups as compared to the control group; and adiponectin levels increased only in the 100nM group as compared to the control group. Conclusion These results demonstrated fast actions of triiodothyronine on the leptin and adiponectin expression, starting at 0.5 hour, at a dose of 1,000nM for leptin and 100nM for adiponectin. Triiodothyronine stimulated or inhibited the expression of adipokines in adipocytes at different times and doses which may be useful to assist in the treatment of obesity, assuming that leptin is increased and adiponectin is decreased, in obesity cases. .

Objetivo Examinar o efeito de diferentes doses de triiodotironina sobre a expressão gênica das adipocinas leptina e adiponectina, em diferentes períodos de tempo, além de avaliar a diferença de expressão entre as duas adipocinas em cada grupo. Métodos Adipócitos 3T3-L1 foram incubados com triiodotironina nas doses fisiológica (10nM) e suprafisiológicas (100nM ou 1.000nM), ou na ausência de triiodotironina (controle, C) durante 0,5, 6 ou 24 horas. O mRNA das adipocinas foi analisado em tempo real, utilizando a reação em cadeia de polimerase. Para as análises dos dados, foi utilizada a análise de variância, complementada com o teste de Tukey, ou o teste t de Student com 5% de significância. Resultados Os níveis de leptina diminuíram no grupo com dose de 1.000nM em 0,5 hora. A adiponectina também diminuiu no grupo com dose de 10nM, porém se elevou com a dose de 100nM. Após 6 horas, ambos os genes foram suprimidos em todas concentrações de hormônio. Em 24 horas, os níveis de leptina foram elevados em 10, 100 e 1.000nM, em relação ao grupo controle. No que concerne à adiponectina, observou-se aumento apenas no grupo cuja dose foi de 100nM, em comparação ao controle. Conclusão Foram demonstradas ações rápidas da triiodotironina sobre a expressão da leptina e da adiponectina, iniciando em 0,5 hora na dose de 1.000nM, para a primeira, e na dose de 100nM, para a segunda. A triiodotironina estimulou ou inibiu a expressão de adipocinas em adipócitos em diferentes tempos e doses, o que pode auxiliar no tratamento da obesidade, levando em consideração que, nesta, a leptina está aumentada e adiponectina, diminuída. .

Polymorphisms in LEPR, PPARG and APM1 genes: associations with energy intake and metabolic traits in young children / Polimorfismos nos genes LEPR, PPARG e APM1: associações com ingestão energética e parâmetros metabólicos em crianças em idade precoce

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) in five genes - leptin, leptin receptor (LEPR), adiponectin (APM1), peroxisome proliferator-activated receptor gamma (PPARG) and uncoupling protein 1 - with anthropometric, metabolic, and dietary parameters in a Southern Brazilian cohort of 325 children followed up from birth to 4 years old. MATERIALS AND METHODS: SNPs were analyzed using polymerase chain reaction-based procedures, and their association with phenotypes was evaluated by t-test, analysis of variance, and general linear models. RESULTS: LEPR223Arg allele (rs1137101) was associated with higher daily energy intake at 4 years of age (P = 0.002; Pcorrected = 0.024). PPARG 12Ala-carriers (rs1801282) presented higher glucose levels than Pro/Pro homozygotes (P = 0.007; Pcorrected = 0.042). CONCLUSIONS: Two of the six studied SNPs presented consistent associations, showing that it is already possible to detect the influences of genetic variants on susceptibility to overweight in 4-year-old children.

OBJETIVO: Avaliar a associação de polimorfismos de nucleotídeo único (SNPs) em cinco genes: leptina, receptor da leptina (LEPR), adiponectina (APM1), receptor ativado por proliferadores de peroxissomas gama (PPARG) e proteína desacopladora 1 com parâmetros antropométricos, metabólicos e dietéticos em uma coorte sul-brasileira composta por 325 crianças acompanhadas desde o nascimento até os 4 anos. MATERIAIS E MÉTODOS: Os SNPs foram analisados por meio da reação em cadeia da polimerase e sua associação com os fenótipos foi avaliada utilizando teste T, análise de variância e análise fatorial. RESULTADOS: O alelo LEPR223Arg (rs1137101) foi associado a uma maior ingestão energética diária aos 4 anos (P = 0,002; Pcorrigido = 0,024). Os portadores do alelo PPARG12Ala (rs1801282) apresentaram maior glicemia em relação aos homozigotos Pro/Pro (P = 0,007; Pcorrigido = 0,042). CONCLUSÕES: Dois dos seis SNPs estudados apresentaram associações consistentes, mostrando que aos 4 anos de idade já é possível detectar as influências de variantes genéticas sobre a suscetibilidade ao excesso de peso.

Association between CDH13 Variants and Cardiometabolic and Vascular Phenotypes in a Korean Population

PURPOSE: Although some CDH13 single nucleotide polymorphisms (SNPs) have been shown to be determinants of blood adiponectin levels, the clinical implications of CDH13 variants are not yet completely understood. The purpose of this study was to evaluate the effects of SNPs of CDH13 on metabolic and vascular phenotypes. MATERIALS AND METHODS: We included 238 hypertensive subjects and 260 age- and sex-matched controls. Seven tagging-SNPs were identified in the CDH13 gene by whole gene sequencing. The association between these SNP variants and the risk of hypertension, metabolic traits, and carotid intima-media thickness (IMT) was examined. RESULTS: Minor allele carriers of rs12444338 had a lower risk of hypertension, but the association turned out just marginal after adjusting confoudners. Blood glucose levels were higher in the minor allele carriers of c.1407C>T (p=0.01), whereas low-density lipoprotein-cholesterol levels were greater in those of rs6565105 (p=0.02). The minor allele of rs1048612 was associated with a higher body mass index (p=0.01). In addition, the mean carotid IMT was significantly associated with rs12444338 (p=0.02) and rs1048612 (p=0.02). CONCLUSION: These results provide evidence that CDH13 variants are associated with metabolic traits and carotid atherosclerosis in Koreans. This study shows the multifaceted effects of CDH13 variants on cardiometabolic risk.

Relationship between polymorphism of insulin receptor gene, and adiponectin gene with PCOS

Polycystic ovary syndrome [PCOS] is a complex disease having both genetic and environmental components and candidate genes on obesity and insulin metabolism have been hypothesized to be involved in its etiology. We examined the possible association of adiponectin and insulin receptor gene polymorphisms with PCOS. A total of 186 women with PCOS using NIH criteria and 156 healthy women were recruited. Their samples were genotyped for the polymorphism in exon 17 and 8 of the insulin receptor gene or exon and intron 2 of the adiponectin gene. The distributions of genotypes and alleles of both polymorphisms were not different in women with PCOS and controls. There was no significant differences on the anthropometric and hormonal profiles of various adiponectin and insulin receptor genes polymorphisms among both groups. Adiponectin and insulin receptor gene polymorphisms are not associated with PCOS in a sample of Iranian population

B-cell-activating factor is a regulator of adipokines and a possible mediator between adipocytes and macrophages

3T3-L1 adipocytes express the B-cell-activating factor (BAFF) and three different BAFF receptors (BAFF-Rs). Furthermore, BAFF expression is regulated by inflammatory modulators, such as tumor necrosis factor-alpha and rosiglitazone. Here we investigated the function of BAFF in 3T3-L1 adipocytes and RAW 264.7 macrophages. We examined adipokine expression in 3T3-L1 adipocytes treated with 10 ng ml-1 BAFF. We also examined inflammatory molecule expression in RAW 264.7 macrophages treated with 10 or 100 ng ml-1 BAFF. We examined BAFF expression in the coculture of 3T3-L1 adipocytes and RAW 264.7 macrophages, as well as in white adipose tissue (WAT) of diet-induced obese (DIO) mice. We found that BAFF decreases leptin and adiponectin expression, but increases the expression of proinflammatory adipokines monocyte chemotactic protein-1, interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and haptoglobin. Coculturing the two cell types resulted in increased BAFF mRNA and protein expression, as well as modulation of BAFF-R mRNA expression in both cell types. These data indicate that BAFF might mediate adipocyte and macrophage interaction. When RAW 264.7 macrophages were treated with BAFF, BAFF-R expression was modulated as in coculture, and nitric oxide synthase and IL-6 expression increased. BAFF expression also increased in WAT of DIO mice. We propose that BAFF can regulate adipokine expression and possibly mediate adipocyte and macrophage interaction.

Associação entre variantes do gene da adiponectina (ADIPOQ): -11391 G/A, -11377 C/G, 45T>G e I164T e os níveis circulantes de adiponectina de alto peso molecular e fatores de risco cardiometabólico / Association between variants of the adiponectin (ADIPOQ) gene: -11 391 G / A, -11 377 C / G, 45T> G and I164T and circulating levels of adiponectin, high molecular weight and cardiometabolic risk factors

A adiponectina, um hormônio produzido pelo tecido adiposo, atua na regulação do metabolismo energético e interfere favoravelmente na sensibilidade à insulina através de suas ações no fígado e musculatura esquelética. Ao contrário da maioria das outras adipocitocinas, associa-se inversamente com a obesidade visceral, resistência à insulina, diabetes tipo 2 e doença cardiovascular. Inúmeros estudos demonstraram nos últimos anos os efeitos de variantes genéticas no gene ADIPOQ sobre os níveis circulantes de adiponectina, resistência à insulina, diabetes e obesidade. Entretanto, além de resultados contraditórios, a maior parte desses estudos foi realizada em populações Caucasianas e Asiáticas. Avaliar, em uma população multiétnica adulta do município do Rio de Janeiro, as possíveis associações das variantes genéticas (-11391 G>A, -11377C>G, +45T>G e T517G) no gene ADIPOQ com o fenótipo obeso, níveis circulantes de adiponectina de alto peso molecular e fatores de risco cardiometabólico. Trata-se de um estudo transversal. Foram estudados 100 indivíduos eutróficos (IMC 18,5 – 24,9 kg/m2, idade: 32,5 + 9,8 anos) e 100 obesos (IMC 30 – 58,2 kg/m2, idade 37,5 + 14,1 anos), igualmente divididos entre homens e mulheres. Os indivíduos obesos apresentaram valores significativamente maiores de circunferência abdominal, pressão arterial sistólica, diastólica e média, glicemia de jejum, triglicerídeos, LDL-colesterol, leptina, insulina, HOMA-IR e proteína C reativa, quando comparados aos eutróficos. Contrariamente, exibiram menores valores de adiponectina e HDL-colesterol. Análises de correlação mostraram relação inversa e significativa entre a adiponectina, circunferência abdominal, insulina, HOMA-IR e pressão arterial. Com os níveis de HDL-colesterol, a correlação foi positiva. Por meio de análise de regressão múltipla foi possível identificar os determinantes dos níveis séricos de adiponecinta. Sexo masculino, circunferência abdominal, HOMA-IR e a variante genética ...

A diponectin, a hormone produced by adipose tissue, acts regulating energy metabolism and insulin sensitivity. Unlike other adipocytokines, adiponectin has an inverse association with visceral obesity, insulin resistance, type 2 diabetes and cardiovascular disease. Recently, many studies have been demonstrating the effects of genetic variants in ADIPOQ gene on the circulating levels of adiponectin, blood pressure values, risk of non-alcoholic steatohepatitis and type 2 diabetes, and the emergence of obese phenotype. However, most of the results are controversial and have been related to studies conducted in Caucasian and Asian populations. The aim of the present study was to evaluate, in a multiethnic adult population of the metropolitan region of Rio de Janeiro, the possible effects of the genetic variants (-11391 G>A, -11377C>G, +45T>G e T517G) in ADIPOQ gene on the obese phenotype, circulating levels of adiponectin and high sensitivity and quantitative C-reactive protein, and cardiometabolic risk factors. We evaluated 100 lean individuals (BMI 18,5 – 24,9 kg/m2, age: 32,5 + 9,8 years) and 100 obese individuals (BMI 30 – 58,2 kg/m2, age 37,5 + 14,1 years), equally distributed men and women. The obese subjects showed high levels of abdominal circunference, blood pressure, fasting glucose, triglycerides, LDL-cholesterol, leptin, insulin, HOMA-IR and C-reactive protein, and exhibited lower levels of HDL-cholesterol and adiponectin, when compared to euthrophic individuals. Correlation analysis showed an inverse relationship between adiponectin and abdominal circumference, insulin, HOMA-IR and blood pressure, and a positive correlation with HDL-cholesterol. Stepwise regression analysis revealed that gender, abdominal circumference, HOMA-IR and the -11391G>A polymorphism were independently related with adiponectin levels. Regarding to the molecular analyses, no association was found between these variants and the obese phenotype. However, the subjects carrying ...

Asociación entre polimorfismos del gen de adiponectina y estado nutricional en escolares de la comuna de Hualpén / Association between adiponectin gene polymorphisms and obesity in school age children from Hualpén, Chile

Background: Several genetic polymorphisms of adiponectin have been associated to metabolic diseases as obesity and co-morbidities. Aim: To investigate if there are associations between +45TG, +276GT, -11,377CG y -11,391GA adiponectin SNPs (single nucleotide polymorphism) with obesity in a Chilean children population. Material and Methods: A case-control study was performed in 241 obese and 126 normal weight children (7-11 years old) from the urban community of Hualpén, Biobío region. Children were classified as normal or obese, according to age and gender-specificpercentiles defined by Centerfor Disease Control and Prevention (CDC). The analysis of serum markers was carried out using commercial kits. Adiponectin polymorphisms were determined through a High Resolution Melting (HRM)-enabled real time PCR and by DNA fragment sequencing. Results: The observed allelic frequencies of the studied SNPs were over 11%. The 11,377CG polymorphism was associated with a high risk of obesity, calculated by the additive inheritance model (odds ratio = 1.389, 95% confidence interval: 1.001-1.929,p = 0.049). Conclusions: Obese school children of the Biobío Region, have an increased risk of carrying the susceptibility allele polymorphism 11377CG of adiponectin gene.