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Sample records for adiponectin adipoq gene

  1. Variants of the Adiponectin (ADIPOQ) and Adiponectin Receptor 1 (ADIPOR1) Genes and Colorectal Cancer Risk

    PubMed Central

    Kaklamani, Virginia G.; Wisinski, Kari B.; Sadim, Maureen; Gulden, Cassandra; Do, Albert; Offit, Kenneth; Baron, John A.; Ahsan, Habibul; Mantzoros, Christos; Pasche, Boris

    2008-01-01

    Context Current epidemiological evidence suggests an association between obesity, hyperinsulinemia, and colorectal cancer risk. Adiponectin is a hormone secreted by the adipose tissue, and serum levels are inversely correlated with obesity and hyperinsulinemia. While there is evidence of an association between circulating adiponectin levels and colorectal cancer risk, no association between genes of the adiponectin pathway and colorectal cancer have been reported to date. Objective To determine the association of 10 haplotype-tagging single-nucleotide polymorphisms (SNPs) of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with colorectal cancer risk. Design, Setting, and Patients Two case-control studies including patients with a diagnosis of colorectal cancer and controls were recruited between 2000 and 2007. Case-control study 1 included a total of 441 patients with a diagnosis of colorectal cancer and 658 controls; both groups were of Ashkenazi Jewish ancestry and from New York, New York. Case-control study 2 included 199 patients with a diagnosis of colorectal cancer and 199 controls from Chicago, Illinois, matched 1:1 for sex, age, and ethnicity. Main Outcome Measures ADIPOQ and ADIPOR1 SNP frequency among cases and controls. Results In study 1, after adjustment for age, sex, and SNPs from the same gene, 3 ADIPOQ SNPs and 1 ADIPOR1 SNP were associated with colorectal cancer risk: rs266729 (adjusted odds ratio [AOR], 0.72; 95% confidence interval [CI], 0.55–0.95) and rs822396 (AOR, 0.37; 95% CI, 0.14–1.00) were associated with decreased risk whereas rs822395 (AOR, 1.76; 95% CI, 1.09–2.84) and rs1342387 (AOR, 1.79; 95% CI, 1.18–2.72) were associated with increased risk. In study 2, after adjustment for age, sex, race, and SNPs from the same gene, the ADIPOQ SNP rs266729 was associated with a decreased colorectal cancer risk of similar magnitude as in study 1 (AOR, 0.52; 95% CI, 0.34–0.78). Combined analysis of both studies shows an

  2. Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity.

    PubMed

    Kyriakou, Theodosios; Collins, Laura J; Spencer-Jones, Nicola J; Malcolm, Claire; Wang, Xiaoling; Snieder, Harold; Swaminathan, Ramasamyiyer; Burling, Keith A; Hart, Deborah J; Spector, Tim D; O'Dell, Sandra D

    2008-01-01

    Adiponectin is an insulin sensitiser in muscle and liver, and low serum levels characterise obesity and insulin resistance. Eight tagging single nucleotide polymorphisms (tSNPs) in the ADIPOQ gene and promoter were selected, and association with serum adiponectin was tested, in two independent samples of Caucasian women: the Chingford Study (n = 808, mean age 62.8 +/- 5.9 years) and Twins UK (n = 2,718, mean age 47.4 +/- 12.6 years). In the Chingford cohort, -11391 G/A, -10066 G/A (rs182052), -7734 C/A (rs16861209), +276 G/T (rs1501299) and +3228 C/T (rs1063537) were significantly associated with fasting serum adiponectin (Ps = 1.00 x 10(-4) to 1.40 x 10(-2)). Associations with all except +3228 C/T were replicated in the Twins UK cohort (Ps = 3.19 x 10(-9) to 6.00 x 10(-3)). In Chingford subjects, the 12 most common 8-SNP haplotypes (frequency 1.90%) explained 2.85% (p = 5.00 x 10(-2)) and in Twins UK subjects, the four most common 5-SNP haplotypes (frequency > 5.00%) explained 1.66% of the variance (p = 5.83 x 10(-7)). To investigate effects of -11391 G/A (rs17300539) and -11377 C/G (rs266729) on promoter activity, 1.2 kb of the ADIPOQ promoter region was cloned in a luciferase reporter plasmid, and the four haplotypes were transfected in differentiated 3T3-L1 adipocytes. No significant allelic effects on promoter activity were found.

  3. Association of Adiponectin Gene (ADIPOQ) rs2241766 Polymorphism with Obesity in Adults: A Meta-Analysis

    PubMed Central

    Wu, Jingjing; Liu, Zheng; Meng, Kai; Zhang, Ling

    2014-01-01

    Background Adiponectin plays an important role in regulating glucose levels and fatty acid oxidation. Multiple studies have assessed the association between rs2241766 polymorphism in the adiponectin (ADIPOQ) gene and obesity susceptibility. However, the results are inconsistent and inconclusive. The aim of this meta-analysis was to investigate this association in adults. Method Several electronic databases were searched for relevant literature published up to November 2013. Statistical analyses were performed using software Review Manager (Version 5.02) and STATA (Version 10.0). The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a random-effects model or a fixed-effect model depending on heterogeneity among studies. Q tests and Egger’s tests were performed to assess heterogeneity and publication bias. Sensitivity analysis was conducted to confirm the reliability and stability of the meta-analysis. Results A total of 2,819 obese and 3,024 controls in 18 case-control studies were included in the meta-analysis. The results indicated that compared with TT genotype, the ADIPOQ-rs2241766 GG genotype was associated with an increased risk for obesity (OR = 1.39, 95% CI: 1.11–1.73, P for heterogeneity = 0.520, I2 = 0%) in overall studies. Whereas, GT genotype was associated with a borderland increased risk for obesity (OR = 1.13, 95% CI: 0.94–1.36, P for heterogeneity = 0.006, I2 = 51%). The susceptibility of obesity was increased based on genotypes of TTADIPOQ-rs2241766 GG genotype increased obesity risk in the Chinese studies (OR = 1.54, 95% CI: 1.19–2.00) but not in the non-Chinese studies (OR = 1.02, 95% CI: 0.66–1.58). Similar results were observed in allelic, recessive, and dominant genetic models. There was no significant evidence of publication bias in the overall, Chinese, and non-Chinese studies (P

  4. Effects of genetic variants in the promoter region of the bovine adiponectin (ADIPOQ) gene on marbling of Hanwoo beef cattle.

    PubMed

    Choi, Yoonjeong; Davis, Michael E; Chung, Hoyoung

    2015-07-01

    This study aimed to verify genetic effects of the bovine adiponectin (ADIPOQ) gene on carcass traits of Hanwoo cattle. The measured carcass traits were marbling score (MAR), backfat thickness (BFT), loineye area (LEA), and carcass weight (CAW). Selection of primers was based on the bovine ADIPOQ sequence, and the analysis amplified approximately 267 and 333 bp genomic segments, including 67 bp of insertions in the promoter region. Sequencing analysis confirmed genetic variants (g.81966235C>T, g.81966377T>C, and g.81966364D>I) that showed significant effects on MAR. The present results suggest that the identified SNPs are useful genetic markers for the improvement of carcass traits in Hanwoo cattle.

  5. No evidence for a role of the peroxisome proliferator-activated receptor gamma (PPARG) and adiponectin (ADIPOQ) genes in antipsychotic-induced weight gain.

    PubMed

    Brandl, Eva J; Tiwari, Arun K; Zai, Clement C; Chowdhury, Nabilah I; Lieberman, Jeffrey A; Meltzer, Herbert Y; Kennedy, James L; Müller, Daniel J

    2014-10-30

    Antipsychotics frequently cause changes in glucose metabolism followed by development of weight gain and/or diabetes. Recent findings from our group indicated an influence of glucose-related genes on this serious side effect. With this study, we aimed to extend previous research and performed a comprehensive study on the peroxisome proliferator-activated receptor gamma (PPARG) and the adiponectin (ADIPOQ) genes. In 216 schizophrenic patients receiving antipsychotics for up to 14 weeks, we investigated single-nucleotide polymorphisms in or near PPARG (N=24) and ADIPOQ (N=18). Statistical analysis was done using ANCOVA in SPSS. Haplotype analysis was performed in UNPHASED 3.1.4 and Haploview 4.2. None of the PPARG or ADIPOQ variants showed significant association with antipsychotic-induced weight gain in our combined sample or in a refined subsample of patients of European ancestry treated with clozapine or olanzapine after correction for multiple testing. Similarly, no haplotype association could withstand multiple test correction. Although we could not find a significant influence of ADIPOQ and PPARG on antipsychotic-induced weight gain, our comprehensive examination of these two genes contributes to understanding the biology of this serious side effect. More research on glucose metabolism genes is warranted to elucidate their role in metabolic changes during antipsychotic treatment.

  6. Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: results of genome-wide association analyses including 4659 European individuals

    PubMed Central

    Heid, Iris M.; Henneman, Peter; Hicks, Andrew; Coassin, Stefan; Winkler, Thomas; Aulchenko, Yurii S.; Fuchsberger, Christian; Song, Kijoung; Hivert, Marie-France; Waterworth, Dawn M.; Timpson, Nicholas J.; Richards, J. Brent; Perry, John R.B.; Tanaka, Toshiko; Amin, Najaf; Kollerits, Barbara; Pichler, Irene; Oostra, Ben A.; Thorand, Barbara; Frants, Rune R.; Illig, Thomas; Dupuis, Josée; Glaser, Beate; Spector, Tim; Guralnik, Jack; Egan, Josephine M.; Florez, Jose C.; Evans, David M.; Soranzo, Nicole; Bandinelli, Stefania; Carlson, Olga D.; Frayling, Timothy M.; Burling, Keith; Smith, George Davey; Mooser, Vincent; Ferrucci, Luigi; Meigs, James B.; Vollenweider, Peter; van Dijk, Ko Willems; Pramstaller, Peter; Kronenberg, Florian; van Duijn, Cornelia M.

    2009-01-01

    Objective Plasma adiponectin is strongly associated with various components of metabolic syndrome, type 2 diabetes and cardiovascular outcomes. Concentrations are highly heritable and differ between men and women. We therefore aimed to investigate the genetics of plasma adiponectin in men and women. Methods We combined genome-wide association scans of three population-based studies including 4659 persons. For the replication stage in 13795 subjects, we selected the 20 top signals of the combined analysis, as well as the 10 top signals with p-values less than 1.0*10-4 for each the men- and the women-specific analyses. We further selected 73 SNPs that were consistently associated with metabolic syndrome parameters in previous genome-wide association studies to check for their association with plasma adiponectin. Results The ADIPOQ locus showed genome-wide significant p-values in the combined (p=4.3*10-24) as well as in both women- and men-specific analyses (p=8.7*10-17 and p=2.5*10-11, respectively). None of the other 39 top signal SNPs showed evidence for association in the replication analysis. None of 73 SNPs from metabolic syndrome loci exhibited association with plasma adiponectin (p>0.01). Conclusions We demonstrated the ADIPOQ gene as the only major gene for plasma adiponectin, which explains 6.7% of the phenotypic variance. We further found that neither this gene nor any of the metabolic syndrome loci explained the sex differences observed for plasma adiponectin. Larger studies are needed to identify more moderate genetic determinants of plasma adiponectin. PMID:20018283

  7. Polymorphisms in the promoter region of the adiponectin (ADIPOQ) gene are presumably associated with transcription level and carcass traits in pigs.

    PubMed

    Cieslak, J; Flisikowska, T; Schnieke, A; Kind, A; Szydlowski, M; Switonski, M; Flisikowski, K

    2013-06-01

    The main goal of this study was to screen for polymorphisms in the porcine adiponectin (ADIPOQ) gene promoter, analyse their influence on transcription and identify any association with production traits in pigs. A 1018-bp region of the ADIPOQ gene promoter was analysed in 113 pigs, and seven novel polymorphisms found. Luciferase assays were performed in HEK293 (human embryonic kidney) cells and primary porcine adipose mesenchymal stem cells (pADMSCs) to investigate their affect on promoter activity. A 16-bp indel (c.-106_-91delGCCAGGGGTGTGAGCC) was found to influence promoter strength in vitro. In the HEK293 cell line, the Del/Del genotype showed greater luciferase activity than did the Ins/Ins genotype (P < 0.01). In pADMSCs, the insertion genotype of the ADIPOQ promoter showed greater luciferase activity than did the deletion genotype (P < 0.01). An association study performed for two novel polymorphisms, c.-67G>A and the 16-bp indel, showed significant correlation with loin measurements in Polish Landrace (P < 0.05) and synthetic line 990 (P < 0.01) pigs.

  8. ADIPOQ, ADIPOR1, and ADIPOR2 Polymorphisms in Relation to Serum Adiponectin Levels and Body Mass Index in Black and White Women

    PubMed Central

    Cohen, Sarah S.; Gammon, Marilie D.; North, Kari E.; Millikan, Robert C.; Lange, Ethan M.; Williams, Scott M.; Zheng, Wei; Cai, Qiuyin; Long, Jirong; Smith, Jeffrey R.; Signorello, Lisa B.; Blot, William J.; Matthews, Charles E.

    2012-01-01

    Adiponectin is an adipose-secreted protein with influence on several physiologic pathways including those related to insulin sensitivity, inflammation, and atherogenesis. Adiponectin levels are highly heritable and several single nucleotide polymorphisms (SNPs) in adiponectin-related genes (ADIPOQ, ADIPOR1, ADIPOR2) have been examined in relation to circulating adiponectin levels and obesity phenotypes, but despite differences in adiponectin levels and obesity prevalence by race, few studies have included black participants. Using cross-sectional interview data and blood samples collected from 990 black and 977 white women enrolled in the Southern Community Cohort Study from 2002 to 2006, we examined 25 SNPs in ADIPOQ, 19 in ADIPOR1, and 27 in ADIPOR2 in relation to serum adiponectin levels and body mass index (BMI) using race-stratified linear regression models adjusted for age and percentage African ancestry. SNP rs17366568 in ADIPOQ was significantly associated with serum adiponectin levels in white women only (adjusted mean adiponectin levels = 15.9 for G/G genotype, 13.7 for A/G, and 9.3 for A/A, p=0.00036). No other SNPs were associated with adiponectin or BMI among blacks or whites. Because adiponectin levels as well as obesity are highly heritable and vary by race but associations with polymorphisms in the ADIPOQ, ADIPOR1, and ADIPOR2 genes have been few in this and other studies, future work including large populations from diverse racial groups is needed to detect additional genetic variants that influence adiponectin and BMI. PMID:21273992

  9. Emerging role of autophagy in mediating widespread actions of ADIPOQ/adiponectin.

    PubMed

    Xu, Aimin; Sweeney, Gary

    2015-04-03

    Autophagy can dictate changes in cell metabolism via numerous mechanisms. ADIPOQ/adiponectin has been extensively characterized to have beneficial metabolic effects, both via INS/insulin-sensitizing and INS-independent actions. Our recent work examined the regulation of skeletal muscle autophagy by ADIPOQ and the functional significance. We showed that ADIPOQ directly stimulates autophagic flux in cultured skeletal muscle cells via an AMPK-dependent signaling pathway leading to phosphorylation of ULK1 (Ser555). Pharmacological inhibition of autophagy or overexpressing an inactive mutant of ATG5 to create an autophagy-deficient cell model reduces INS sensitivity. A high-fat diet (HFD) does not induce skeletal muscle autophagy in Adipoq knockout (Ad-KO) mice, whereas it does in wild-type (WT) mice, although ADIPOQ replenishment in Ad-KO mice stimulates autophagy. Changes in skeletal muscle autophagy correlate well with peripheral INS sensitivity and glucose metabolism. Thus, ADIPOQ stimulates autophagic flux in skeletal muscle, which likely represents one important mechanism mediating multiple favorable metabolic effects.

  10. Empirical Characteristics of Family-Based Linkage to a Complex Trait: the ADIPOQ Region and Adiponectin Levels

    PubMed Central

    Hellwege, Jacklyn N.; Palmer, Nicholette D.; Brown, W. Mark; Ziegler, Julie T.; An, S. Sandy; Guo, Xiuqing; Chen, Y.-D. Ida; Taylor, Kent; Hawkins, Gregory A.; Ng, Maggie C.Y.; Speliotes, Elizabeth K.; Lorenzo, Carlos; Norris, Jill M.; Rotter, Jerome I.; Wagenknecht, Lynne E.; Langefeld, Carl D.; Bowden, Donald W.

    2014-01-01

    We previously identified a low frequency (1.1%) coding variant (G45R; rs200573126) in the adiponectin gene (ADIPOQ) which was the basis for a multipoint microsatellite linkage signal (LOD=8.2) for plasma adiponectin levels in Hispanic families. We have empirically evaluated the ability of data from targeted common variants, exome chip genotyping, and genome-wide association study (GWAS) data to detect linkage and association to adiponectin protein levels at this locus. Simple two-point linkage and association analyses were performed in 88 Hispanic families (1150 individuals) using 10,958 SNPs on chromosome 3. Approaches were compared for their ability to map the functional variant, G45R, which was strongly linked (two-point LOD=20.98) and powerfully associated (p-value=8.1×10−50). Over 450 SNPs within a broad 61 Mb interval around rs200573126 showed nominal evidence of linkage (LOD>3) but only four other SNPs in this region were associated with p-values<1.0×10−4. When G45R was accounted for, the maximum LOD score across the interval dropped to 4.39 and the best p-value was 1.1×10−5. Linked and/or associated variants ranged in frequency (0.0018 to 0.50) and type (coding, non-coding) and had little detectable linkage disequilibrium with rs200573126 (r2<0.20). In addition, the two-point linkage approach empirically outperformed multipoint microsatellite and multipoint SNP analysis. In the absence of data for rs200573126, family-based linkage analysis using a moderately dense SNP dataset, including both common and low frequency variants, resulted in stronger evidence for an adiponectin locus than association data alone. Thus, linkage analysis can be a useful tool to facilitate identification of high impact genetic variants. PMID:25447270

  11. Adiponectin gene variant interacts with fish oil supplementation to influence serum adiponectin in older individuals.

    PubMed

    Alsaleh, Aseel; Crepostnaia, Daria; Maniou, Zoitsa; Lewis, Fiona J; Hall, Wendy L; Sanders, Thomas A B; O'Dell, Sandra D

    2013-07-01

    Marine n3 polyunsaturated fatty acids (PUFAs) activate the transcription factor peroxisome proliferator-activated receptor (PPARγ), which modulates the expression of adiponectin. We investigated the interaction of dietary n3 PUFAs with adiponectin gene (ADIPOQ) single nucleotide polymorphism (SNP) genotypes as a determinant of serum adiponectin concentration. The Modulation of Atherosclerosis Risk by Increasing Doses of n3 Fatty Acids study is a parallel design, double-blind, controlled trial. Serum adiponectin was measured in 142 healthy men and 225 women aged 45-70 y randomized to treatment with doses of 0.45, 0.9, and 1.8 g/d 20:5n3 and 22:6n3 (1.51:1), or placebo for 12 mo. The 310 participants who completed the study were genotyped for 5 SNPs at the ADIPOQ locus: -11391 G/A (rs17300539), -11377 C/G (rs266729), -10066 G/A (rs182052), +45 T/G (rs2241766), and +276 G/T (rs1501299). The -11391 A-allele was associated with a higher serum adiponectin concentration at baseline (n = 290; P < 0.001). The interaction between treatment and age as a determinant of adiponectin was significant in participants aged >58 y after the highest dose (n = 92; P = 0.020). The interaction between +45 T/G and treatment and age was a nominally significant determinant of serum adiponectin after adjustment for BMI, gender, and ethnicity (P = 0.029). Individuals homozygous for the +45 T-allele aged >58 y had a 22% increase in serum adiponectin concentration compared with baseline after the highest dose (P-treatment effect = 0.008). If substantiated in a larger sample, a diet high in n3 PUFAs may be recommended for older individuals, especially those of the +45 TT genotype who have reported increased risk of hypoadiponectinemia, type 2 diabetes, and obesity.

  12. In silico Evaluation of Nonsynonymous Single Nucleotide Polymorphisms in the ADIPOQ Gene Associated with Diabetes, Obesity, and Inflammation

    PubMed Central

    Narayana Swamy, A; Valasala, Harika; Kamma, Sreenivasulu

    2015-01-01

    Background: The human ADIPOQ gene encodes adiponectin protein hormone, which is involved in regulating glucose levels as well as fatty acid breakdown. It is exclusively produced by adipose tissue and abundantly present in the circulation, with concentration of around 0.01% of total serum proteins, with important effect on metabolism. Methods: Most deleterious nonsynonymous single nucleotide polymorphisms in the coding region of the ADIPOQ gene were investigated using SNP databases, and detected nonsynonymous variants were analyzed in silico from the standpoint of relevant protein function and stability by using SIFT, PolyPhen-2, PROVEAN and MUpro, I-Mutant2.0 tools, respectively. Result: A total of 58 nonsynonymous SNPs consisting of 55 missense variations, 3 nonsense variations were found in the ADIPOQ gene. Next, 14 of the 55 missense variants were predicted to be damaging or deleterious by three different software programs (PolyPhen-2, SIFT, and PROVEAN), and 38 of them were predicted to be less stable (I-Mutant 2.0 and MUpro software). Totally, 10 variants out of 55 missense variants were predicted to be both deleterious and reduce protein stability. Additionally, 3 nonsense variants were predicted to produce a truncated ADIPOQ protein. RMSD and total energy were calculated for 4 nsSNPs out of 10 nsSNPs which were both deleterious and showed a decrease in protein stability. Conclusion: rs144526209 has high root-mean-square deviation (RMSD) and lower total energy value compared to the native modeled structure. It was concluded that this nsSNP, potentially functional and polymorphic in the ADIPOQ gene, might be associated with diabetes, obesity, and inflammation. PMID:26306152

  13. Associations between single-nucleotide polymorphisms of ADIPOQ, serum adiponectin and increased type 2 diabetes mellitus risk in Bahraini individuals.

    PubMed

    Al Hannan, F A; O'Farrell, P A; Morgan, M P; Tighe, O; Culligan, K G

    2016-11-02

    This study aimed to estimate the frequency of the SNPs (+45T>G and +276G>T) genotypes and investigate the association between the two SNPs and adiponectin concentration, metabolic parameters and risk of T2DM in the Bahraini population. We genotyped the two ADIPOQ SNPs in 140 unrelated T2DM patients and 66 nondiabetic controls using the polymerase chain reaction-restriction fragment length polymorphism assay. Lipid profile was measured by enzymatic methods. Total serum adiponectin levels were measured by immunoassay. T2DM patients had reduced adiponectin levels compared with controls. +45T>G was more prevalent in patients than controls. The rare G allele of +45T>G occurred more frequently than the common T allele in T2DM patients compared with controls, and was associated with lower serum adiponectin levels. There was no significant difference in allele and genotype frequencies of +276G>T between type T2DM patients and controls. There was no association between both SNPs and metabolic parameters.

  14. Haplotype combination of polymorphisms in the ADIPOQ gene promoter is associated with growth traits in Qinchuan cattle.

    PubMed

    Zhang, Liangzhi; Li, Mijie; Lai, Xinsheng; Yang, Mingjuan; Xu, Yao; Hua, Liushuai; Lan, Xianyong; Zhang, Chunlei; Chen, Hong

    2013-07-01

    Adiponectin modulates lipid and glucose metabolism in adipose tissues and is also related to bone metabolism. Polymorphisms in the ADIPOQ gene likely have an impact on growth traits in cattle. In this study, we examined the relationship between ADIPOQ polymorphisms and body measurement parameters in Chinese beef cattle. First, we sequenced ADIPOQ and 1.2 kb of DNA upstream of its promoter, and we found 14 polymorphisms. With the luciferase reporter assay, we showed that the two polymorphisms SNP PR_-135 A>G and PR_-68 G>C, which are located in the core region of promoter, influence promoter activity of ADIPOQ. Second, we identified three haplotypes involved in these two polymorphic sites: A (A-135/C-68), B (A-135/G-68), and C (G-135/G-68). Haplotypes B and C are major haplotypes in five Chinese populations of cattle (Qinchuan, Nanyang, Jiaxian, Hazakh, and Chinese Holstein). We studied the effects of these three haplotypes on body measurements, gene expression, and promoter activity, and we found that the genotypes are associated with body measurement parameters in Qinchuan cattle. Individuals with genotype BC (AG/GG) had significantly higher body height and heart girth than others, and this result may be interpreted by the following two observations. The promoter activity with haplotype B (A/G) is significantly higher than those with A (A/C) and C (G/G) in driving reporter gene transcription; the ADIPOQ mRNA level in cattle with genotype BC (AG/GG) is relatively lower than that in cattle with genotype BB (AA/GG).

  15. Implications of critical PPARγ2, ADIPOQ and FTO gene polymorphisms in type 2 diabetes and obesity-mediated susceptibility to type 2 diabetes in an Indian population.

    PubMed

    Phani, Nagaraja M; Vohra, Manik; Rajesh, Somyasree; Adhikari, Prabha; Nagri, Shivashankara K; D'Souza, Sydney C; Satyamoorthy, Kapaettu; Rai, Padmalatha S

    2016-02-01

    Peroxisome proliferator-activated receptors (PPARγ), adiponectin (ADIPOQ) and fat mass and obesity-associated gene (FTO) have been reported as a key candidate genes for obesity, type 2 diabetes (T2D) susceptibility and insulin resistance, and we hypothesize that in the background of obesity, the effect of PPARγ2 (rs1801282), ADIPOQ (rs16861194) and FTO (rs9939609) variant could potentially influence T2D susceptibility. To decipher a more accurate estimation toward its population-specific impact of these variants toward susceptibility to T2D, a case-control study, systematic review and a meta-analysis was performed in a South Asian population. A case-control analysis of 518 T2D cases and 518 controls of Karnataka origin were performed to analyze the association of PPARγ2 (rs1801282), ADIPOQ (rs16861194) and FTO (rs9939609) on the risk of T2D. In addition, a systematic review and meta-analysis for PPARγ2 (rs1801282) and FTO (rs9939609) was elucidated from Asian population. Our investigation showed that PPARγ2 (rs1801282) and FTO (rs9939609) are associated with T2D susceptibility. When T2D cohort was further stratified according to the obesity status, PPARγ2 (rs1801282) and FTO (rs9939609) showed association with T2D only in the obese diabetic group and ADIPOQ (rs16861194) showed no difference in risk of susceptibility to the disease. The meta-analysis of PPARγ2 (rs1801282) showed population-specific association for T2D susceptibility as opposed to FTO (rs9939609) which showed no difference in population effect toward T2D susceptibility. In conclusion, our study showed that PPARγ2 (rs1801282) and FTO (rs9939609) variants are associated with T2D susceptibility when associated with adiposity in Indian population.

  16. TOX and ADIPOQ Gene Polymorphisms Are Associated with Antipsychotic-Induced Weight Gain in Han Chinese

    PubMed Central

    Li, Shen; Xu, Chengai; Tian, Yuan; Wang, Xueshi; Jiang, Rui; Zhang, Miaomiao; Wang, Lili; Yang, Guifu; Gao, Ying; Song, Chenyu; He, Yukun; Zhang, Ying; Li, Jie; Li, Wei-Dong

    2017-01-01

    To find the genetic markers related to the antipsychotic-induced weight gain (AIWG), we analyzed associations among candidate gene single-nucleotide polymorphisms (SNPs) and quantitative traits of weight changes and lipid profiles in a Chinese Han population. A total of 339 schizophrenic patients, including 86 first-episode patients (FEPs), meeting the entry criteria were collected. All patients received atypical antipsychotic drug monotherapy and hospitalization and were followed for 12 weeks. Forty-three SNPs in 23 candidate genes were calculated for quantitative genetic association with AIWG, performed by PLINK. The TOX gene SNP rs11777927 (P = 0.009) and the ADIPOQ gene SNP rs182052 (P = 0.019) were associated with AIWG (in body mass index, BMI). In addition, the BDNF SNP rs6265 (P = 0.002), BDAF SNP rs11030104 SNP (P = 0.001), and ADIPOQ SNPs rs822396 (P = 0.003) were significantly associated with the change of waist-to-hip ratio (WHR) induced by atypical antipsychotics. These results were still significant after age and gender adjustments. These findings provide preliminary evidence supporting the role of TOX, ADIPOQ and BDNF in weight and WHR gain induced by atypical antipsychotics. PMID:28327672

  17. ADIPOQ Polymorphisms, Monounsaturated Fatty Acids, and Obesity Risk: The GOLDN Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To explore whether dietary fat modulates the association of genetic variations at ADIPOQ locus with obesity traits in White US subjects. Methods and Procedures: we genotyped two promoter single nucleotide polymorphisms (SNPs) at adiponectin gene, -11391G>A and -1137C>G, in 1083 participan...

  18. ADIPOQ polymorphisms are associated with insulin resistance in Japanese women.

    PubMed

    Kitamoto, Aya; Kitamoto, Takuya; So, Rina; Matsuo, Tomoaki; Nakata, Yoshio; Hyogo, Hideyuki; Ochi, Hidenori; Nakamura, Takahiro; Kamohara, Seika; Miyatake, Nobuyuki; Kotani, Kazuaki; Mineo, Ikuo; Wada, Jun; Ogawa, Yuji; Yoneda, Masato; Nakajima, Atsushi; Funahashi, Tohru; Miyazaki, Shigeru; Tokunaga, Katsuto; Masuzaki, Hiroaki; Ueno, Takato; Chayama, Kazuaki; Hamaguchi, Kazuyuki; Yamada, Kentaro; Hanafusa, Toshiaki; Oikawa, Shinichi; Sakata, Toshiie; Tanaka, Kiyoji; Matsuzawa, Yuji; Hotta, Kikuko

    2015-01-01

    Visceral fat accumulation contributes to the development of insulin resistance, leading to metabolic syndrome. Adiponectin provides a link between visceral fat accumulation and insulin resistance. In addition to environmental factors, genetic factors play important roles in visceral fat accumulation and circulating adiponectin levels. Genome-wide association studies (GWASs) have identified genetic variations in the adiponectin, C1Q and collagen domain containing (ADIPOQ) gene that are associated with adiponectin levels. In this study, we investigated whether ADIPOQ single nucleotide polymorphisms (SNPs) were associated with visceral fat accumulation and insulin resistance. We measured the visceral fat area (VFA) by computed tomography (CT) and examined the presence of the insulin resistance-related phenotype (fasting plasma glucose, fasting insulin, and homeostasis model assessment-insulin resistance [HOMA-IR]) in a set of Japanese individuals (731 men and 864 women) who were genotyped for seven ADIPOQ SNPs reported by recent GWASs (namely, rs6810075, rs10937273, rs1648707, rs864265, rs182052, rs17366568, and rs6773957). SNPs associated with the phenotype (P < 0.05) were then evaluated by association analysis using a second set of the study participants (383 men and 510 women). None of the SNPs was associated with body mass index (BMI) or VFA in men or women. However, the adiponectin-decreasing alleles of rs10937273 and rs1648707 were significantly associated with HOMA-IR (P = 0.0030 and P = 0.00074, respectively) in women, independently of BMI. These SNPs were significantly associated with decreased adiponectin levels in women. Our results suggested that rs10937273 and rs1648707 may affect insulin sensitivity by regulating adiponectin production by adipose tissue in women.

  19. A Validation Study of Adiponectin rs266729 Gene Variant with Type 2 Diabetes, Obesity, and Metabolic Phenotypes in a Taiwanese Population.

    PubMed

    Hsiao, Tun-Jen; Lin, Eugene

    2016-12-01

    Previous data suggesting that a single nucleotide polymorphism (SNP), rs266729, in the adiponectin C1Q and collagen domain containing (ADIPOQ) gene was associated with type 2 diabetes (T2D) have been inconsistent, especially in Asian populations. In this replication study, we aimed to reassess whether the ADIPOQ rs266729 SNP is associated with T2D, obesity, and T2D/obesity-related metabolic traits in a Taiwanese population. A total of 1047 Taiwanese subjects were analyzed. The ADIPOQ rs266729 SNP was genotyped by the Taqman assay. T2D/obesity-related metabolic traits such as triglyceride, waist circumference, systolic and diastolic blood pressure, total cholesterol, creatinine, alanine aminotransferase, and fasting glucose were measured. Our data revealed that the ADIPOQ rs266729 SNP exhibited no association with T2D among the subjects. In addition, no evidence for an association with obesity (BMI ≧27 kg/m(2)) was found for the ADIPOQ rs266729 SNP. Moreover, the ADIPOQ rs266729 SNP did not show any association with T2D/obesity-related metabolic traits among the complete subjects. However, we found an effect modification of obesity on the association between the ADIPOQ rs266729 SNP and total cholesterol (P = 0.00068) only in obese participants after adjusting for age, gender, BMI, and T2D status. Our study indicates that the ADIPOQ rs266729 SNP may influence T2D/obesity-related metabolic traits such as total cholesterol in obese Taiwanese subjects (but not in non-obese subjects).

  20. Association of ADIPOQ, OLR1 and PPARGC1A gene polymorphisms with growth and carcass traits in Nelore cattle.

    PubMed

    Fonseca, Patrícia D da S; de Souza, Fábio R P; de Camargo, Gregório M F; Gil, Fernanda M M; Cardoso, Diercles F; Zetouni, Larissa; Braz, Camila U; Boligon, Arione A; Branco, Renata H; de Albuquerque, Lucia G; Mercadante, Maria E Z; Tonhati, Humberto

    2015-06-01

    In beef cattle farming, growth and carcass traits are important for genetic breeding programs. Molecular markers can be used to assist selection and increase genetic gain. The ADIPOQ, OLR1 and PPARGC1A genes are involved in lipid synthesis and fat accumulation in adipose tissue. The objective of this study was to identify polymorphisms in these genes and to assess the association with growth and carcass traits in Nelore cattle. A total of 639 animals were genotyped by PCR-RFLP for rs208549452, rs109019599 and rs109163366 in ADIPOQ, OLR1 and PPARGC1A gene, respectively. We analyzed the association of SNPs identified with birth weight, weaning weight, female yearling weight, female hip height, male yearling weight, male hip height, loin eye area, rump fat thickness, and backfat thickness. The OLR1 marker was associated with rump fat thickness and weaning weight (P < 0.05) and the PPARGC1 marker was associated with female yearling weight.

  1. Association of ADIPOQ, OLR1 and PPARGC1A gene polymorphisms with growth and carcass traits in Nelore cattle

    PubMed Central

    Fonseca, Patrícia D. da S.; de Souza, Fábio R.P.; de Camargo, Gregório M.F.; Gil, Fernanda M.M.; Cardoso, Diercles F.; Zetouni, Larissa; Braz, Camila U.; Boligon, Arione A.; Branco, Renata H.; de Albuquerque, Lucia G.; Mercadante, Maria E.Z.; Tonhati, Humberto

    2015-01-01

    In beef cattle farming, growth and carcass traits are important for genetic breeding programs. Molecular markers can be used to assist selection and increase genetic gain. The ADIPOQ, OLR1 and PPARGC1A genes are involved in lipid synthesis and fat accumulation in adipose tissue. The objective of this study was to identify polymorphisms in these genes and to assess the association with growth and carcass traits in Nelore cattle. A total of 639 animals were genotyped by PCR-RFLP for rs208549452, rs109019599 and rs109163366 in ADIPOQ, OLR1 and PPARGC1A gene, respectively. We analyzed the association of SNPs identified with birth weight, weaning weight, female yearling weight, female hip height, male yearling weight, male hip height, loin eye area, rump fat thickness, and backfat thickness. The OLR1 marker was associated with rump fat thickness and weaning weight (P < 0.05) and the PPARGC1 marker was associated with female yearling weight. PMID:25853056

  2. Associations between polymorphisms of the ADIPOQ gene and hypertension risk: a systematic and meta-analysis

    PubMed Central

    Fan, Weina; Qu, Xiaowei; Li, Jing; Wang, Xingning; Bai, Yanping; Cao, Qingmei; Ma, Liqun; Zhou, Xiaoyao; Zhu, Wei; Liu, Wei; Ma, Qiang

    2017-01-01

    ADIPOQ gene polymorphisms have been indicated to be associated with hypertension; however, published studies have reported inconsistent results. Eligible studies were retrieved by searching the PubMed, Embase and China National Knowledge Infrastructure databases. The case group consisted of patients with hypertension, and the control group consisted of subjects with normal blood pressure. Based on eleven published articles, involving 4837 cases and 5618 controls, the pooled results from rs2241766 polymorphism showed increased risk in the allelic model (G VS T: OR = 1.16, 95%CI = 1.06–1.27), recessive model (GG VS GT + TT: OR = 1.34, 95%CI = 1.10–1.63), dominant model (GG + GT VS TT: OR = 1.15, 95%CI = 1.02–1.30) and homozygote model (GG VS TT: OR = 1.38, 95%CI = 1.21–1.69). In addition, rs266729 polymorphism showed increased risk for hypertension in the recessive model (GG VS GC + CC: OR = 1.43, 95%CI = 1.02–2.01). In the Caucasian subgroup, rs1501299 polymorphism showed decreased risk of hypertension in the allelic model (T VS G: OR = 0.75, 95%CI = 0.58–0.97), dominant model (TT + TG VS GG: OR = 0.83, 95%CI = 0.71–0.98) and heterozygote model (TG VS GG: OR = 0.82, 95%CI = 0.68–0.99). The rs2241766 polymorphism was associated with a significant increase in hypertension risk based on our analysis. Moreover, an increased risk of rs266729 in hypertension patients was also detected. Our meta-analysis suggests that the rs1501299 polymorphism may play a protective role in hypertension in Caucasian subgroup; however, this finding requires further study. PMID:28181566

  3. Adiponectin Gene Variants Are Associated with Insulin Sensitivity in Response to Dietary Fat Consumption in Caucasian Men2

    PubMed Central

    Pérez-Martínez, Pablo; López-Miranda, José; Cruz-Teno, Cristina; Delgado-Lista, Javier; Jiménez-Gómez, Yolanda; Fernández, Juan Marcelo; Gómez, Maria José; Marín, Carmen; Pérez-Jiménez, Francisco; Ordovás, José María

    2008-01-01

    Adiponectin (adipoQ) gene variants have been associated with type 2 diabetes mellitus and insulin resistance. Our aim was to examine whether the presence of several polymorphisms at the adipoQ gene locus (-11391 G > A, 11377 C > G, 45 T > G, and 276 G > T) influences the insulin sensitivity to dietary fat. Healthy volunteers (30 men and 29 women) consumed 3 diets for 4 wk each: an initial period during which all subjects consumed a SFA-rich diet (38% total fat, 20% SFA), followed by a carbohydrate-rich diet (CHO) (30% total fat, 55% carbohydrate) or a monounsaturated fatty acid (MUFA)-rich diet (38% total fat, 22% MUFA) following a randomized, crossover design. After participants consumed each diet, we tested peripheral insulin sensitivity with the insulin suppression test and measured plasma adiponectin concentrations. C/C homozygous men for the -11377 C > G single nucleotide polymorphism (SNP) had a significantly greater decrease in the steady-state plasma glucose concentrations when changing from the SFA-rich (8.95 ± 0.6 mmol/L) to the MUFA-rich (6.04 ± 0.31 mmol/L) and CHO-rich (6.35 ± 0.38 mmol/L) diets than did those carrying the minor G allele (SFA, 6.65 ± 0.4 mmol/L; MUFA, 6.45 ± 0.4 mmol/L; CHO, 5.83 ± 0.3 mmol/L) (P sex × gene × diet interaction = 0.016). These differences did not occur in female participants. Furthermore, C/C men had lower plasma adiponectin concentrations than did C/C women (P sex × gene interaction = 0.015), independently of the dietary fat consumed. None of the variables examined were significantly associated with -11426 A > G, 45T > G, or 276 G > T SNP. In conclusion, C/C homozygous men for the -11377 C > G SNP at adipoQ gene were significantly less insulin resistant after consumption of the MUFA- and CHO-rich diets compared with the SFA-rich diet. This information should help in the identification of vulnerable populations or persons who will benefit from more personalized and mechanism-based dietary recommendations. PMID

  4. Family-Based Association Study of rs17300539 and rs12495941 Polymorphism in Adiponectin Gene and Polycystic Ovary Syndrome in a Chinese Population

    PubMed Central

    Sun, Xianchang; Wu, Xingguo; Duan, Yunmin; Liu, Guanghai; Yu, Xinyan; Zhang, Wenjuan

    2017-01-01

    Backgriond Polycystic ovary syndrome (PCOS) is a complex disease that has both genetic and environmental components. Adiponectin plays an important role in the regulation of insulin sensitivity and insulin resistance (IR) in PCOS. The aim of this study was to determine 2 single-nucleotide polymorphisms (SNPs) variants (rs12495941 and rs17300539) of the adiponectin gene (ADIPOQ) in polycystic ovary syndrome (PCOS) families. Material/Methods We recruited 197 PCOS probands, their biological parents, and 192 controls. Anthropometric variables, including hip circumference (HC) and waist circumference (WC), were measured in all subjects during their first visit to the outpatient department. Serum T, FBG, FINS, TC, TG, LDL, and HDL levels were measured. PCOS patients were divided into 2 groups based on BMI: group A (BMI <25 kg/m2) and group B (BMI ≥25 kg/m2). Parents of PCOS were accordingly categorized into group C and group D (fathers), and group E and group F (mothers). The associations among ADIPOQ rs12495941, rs17300539, and PCOS were analyzed using the transmission disequilibrium test (TDT). Results A significant association was found between SNP rs17300539 and PCOS in our Chinese population. The levels of TG and FINS and the genotype frequencies of rs17300539 are significantly different between overweight and lean PCOS. No significant association was detected for rs12495941. Conclusions TDT confirms that rs17300539 of ADIPOQ is strongly associated with the risk of PCOS in a Chinese Han population, but rs12495941 of ADIPOQ is not associated with the occurrence of PCOS. PMID:28060790

  5. Novel Locus FER Is Associated With Serum HMW Adiponectin Levels

    PubMed Central

    Qi, Lu; Menzaghi, Claudia; Salvemini, Lucia; De Bonis, Concetta; Trischitta, Vincenzo; Hu, Frank B.

    2011-01-01

    OBJECTIVE High molecular weight (HMW) adiponectin is a predominant isoform of circulating adiponectin and has been related to type 2 diabetes. Previous linkage studies suggest that different genetic components might be involved in determining HMW and total adiponectin levels. RESEARCH DESIGN AND METHODS We performed a genome-wide association study (GWAS) of serum HMW adiponectin levels in individuals of European ancestry drawn from the Nurses’ Health Study (NHS) (N = 1,591). The single nucleotide polymorphisms (SNPs) identified in the GWAS analysis were replicated in an independent cohort of Europeans (N = 626). We examined the associations of the identified variations with diabetes risk and metabolic syndrome. RESULTS We identified a novel locus near the FER gene (5q21) at a genome-wide significance level, best represented by SNP rs10447248 (P = 4.69 × 10−8). We also confirmed that variations near the adiponectin-encoding ADIPOQ locus (3q27) were related to serum HMW adiponectin levels. In addition, we found that FER SNP rs10447248 was related to HDL cholesterol levels (P = 0.009); ADIPOQ variation was associated with fasting glucose (P = 0.04), HDL cholesterol (P = 0.04), and a metabolic syndrome score (P = 0.002). CONCLUSIONS Our results suggest that different loci may be involved in regulation of circulating HMW adiponectin levels and provide novel insight into the mechanisms that affect HMW adiponectin homeostasis. PMID:21700879

  6. Interaction between β-hexachlorocyclohexane and ADIPOQ genotypes contributes to the risk of type 2 diabetes mellitus in East Chinese adults

    NASA Astrophysics Data System (ADS)

    Li, Shushu; Wang, Xichen; Yang, Lu; Yao, Shen; Zhang, Ruyang; Xiao, Xue; Zhang, Zhan; Wang, Li; Xu, Qiujin; Wang, Shou-Lin

    2016-11-01

    Growing evidence links environmental exposure to hexachlorocyclohexanes (HCHs) to the risk of type 2 diabetes mellitus (T2DM), and ADIPOQ that encodes adiponectin is considered as an important gene for T2DM. However, the role of ADIPOQ-HCH interaction on T2DM risk remains unclear. Thus, a paired case-control study was conducted in an East Chinese community. A total of 1446 subjects, including 723 cases and 723 controls matched on age, gender and residence, were enrolled, and 4 types of HCH isomers were measured in serum samples using GC-MS/MS. Additionally, 4 candidate ADIPOQ SNPs (rs182052, rs266729, rs6810075, and rs16861194) were genotyped by TaqMan assay, and plasma adiponectin was measured using ELISA. No associations between 4 SNPs and T2DM risk were found, but T2DM risk significantly increased with serum levels of β-HCH (P < 0.001). Furthermore, the synergistic interaction between β-HCH and rs182052 significantly increased T2DM risk (OR I-additive model = 2.20, OR I-recessive model = 2.13). Additionally, individuals carrying only rs182052 (A allele) with high levels of β-HCH had significant reduction in adiponectin levels (P = 0.016). These results indicate that the interaction between rs182052 and β-HCH might increase the risk of T2DM by jointly decreasing the adiponectin level and potentially trigger T2DM development.

  7. Gene Polymorphisms of FABP2, ADIPOQ and ANP and Risk of Hypertriglyceridemia and Metabolic Syndrome in Afro-Caribbeans

    PubMed Central

    Rambhojan, Christine; Joannes, Marie-Odile; Maimaitiming-Madani, Suliya; Donnet, Jean-Paul; Marianne-Pépin, Thérèse; Chout, Roger; Roussel, Ronan; Foucan, Lydia

    2016-01-01

    Objectives The metabolic syndrome (MetS) is a cluster of metabolic abnormalities and cardiovascular risk factors that are highly heritable and polygenic. We investigated the association of allelic variants of three candidate genes, rs1799883-FABP2, rs1501299-ADIPOQ and rs5065-ANP with MetS and its components, individually and in combination, using a genetic risk score. Methods A cross-sectional study was conducted in 462 Afro-Caribbeans subjects without cardiovascular complications or lipid-lowering medications. Cardiovascular risk factors and MetS components (NCEP-ATPIII criteria) were recorded. The 3 SNPs were genotyped. The genetic risk score was calculated by summing the number of risk alleles at each locus. Logistic regressions were used. Results Fifty-eight participants (12.6%) were diabetics and 116 (25.1%) had a MetS. In a dominant model, rs1799883 was associated with hypertriglyceridemia (OR 2.22; P = 0.014) and hypertriglyceridemic waist (HTGW), (P = 0.014) but not significantly with overweight (P = 0.049), abdominal obesity (P = 0.033) and MetS (P = 0.068). In a dominant model, the OR of MetS and HTGW for rs1501299 were 1.80 (P = 0.028) and 2.19 (P = 0.040) respectively. In a recessive model, the OR of hypertriglyceridemia for rs5065 was 1.94 (P = 0.075). The genetic risk score was significantly associated with MetS. Subjects carrying 4–5 risk alleles (18.8%) had a nearly 2.5-fold-increased risk of MetS compared to those carrying 0–1 risk allele (24.3%): OR 2.31; P = 0.025. Conclusions This study supports the association of FABP2, ANP and ADIPOQ gene variants with MetS or its components in Afro-Caribbeans and suggests a cumulative genetic influence of theses variants on this syndrome and a potential effect on lipid metabolism. PMID:27684940

  8. Exercise improves adiponectin concentrations irrespective of the adiponectin gene polymorphisms SNP45 and the SNP276 in obese Korean women.

    PubMed

    Lee, Kyoung-Young; Kang, Hyun-Sik; Shin, Yun-A

    2013-03-10

    The effects of exercise on adiponectin levels have been reported to be variable and may be attributable to an interaction between environmental and genetic factors. The single nucleotide polymorphisms (SNP) 45 (T>G) and SNP276 (G>T) of the adiponectin gene are associated with metabolic risk factors including adiponectin levels. We examined whether SNP45 and SNP276 would differentially influence the effect of exercise training in middle-aged women with uncomplicated obesity. We conducted a prospective study in the general community that included 90 Korean women (age 47.0±5.1 years) with uncomplicated obesity. The intervention was aerobic exercise training for 3 months. Body composition, adiponectin levels, and other metabolic risk factors were measured. Prior to exercise training, only body weight differed among the SNP276 genotypes. Exercise training improved body composition, systolic blood pressure, maximal oxygen consumption, high-density lipoprotein cholesterol, and leptin levels. In addition, exercise improved adiponectin levels irrespective of weight gain or loss. However, after adjustments for age, BMI, body fat (%), and waist circumference, no differences were found in obesity-related characteristics (e.g., adiponectin) following exercise training among the SNP45 and the 276 genotypes. Our findings suggest that aerobic exercise affects adiponectin levels regardless of weight loss and this effect would not be influenced by SNP45 and SNP276 in the adiponectin gene.

  9. Association Between Single Nucleotide Polymorphism +276G > T (rs1501299) in ADIPOQ and Endometrial Cancer.

    PubMed

    Bieńkiewicz, Jan; Smolarz, Beata; Malinowski, Andrzej

    2016-01-01

    Current literature gives evidence of an indisputable role adiponectin plays in adipose tissue metabolism and obesity-related diseases. Moreover, latest research efforts focus on linking genetic markers of this adipocytokine's gene (ADIPOQ) with cancer. Aim of this study was to determine the genotype distribution of single nucleotide polymorphism +276G > T (rs1501299) in ADIPOQ and an attempt to identify the impact this polymorphism exerts on endometrial cancer risk in obese females. The test group comprised 90 women treated surgically for endometrial cancer between 2000 and 2012 in the Department of Surgical & Endoscopic Gynecology and Gynecologic Oncology, Polish Mothers' Memorial Hospital - Research Institute, Lodz, Poland. 90 individuals treated in the parallel period for uterine fibroids constituted the control group. Patients within both groups were stratified according to BMI into: lean, overweight and obese subjects. Statistical analysis was performed between two major groups and, furthermore, within the abovementioned subgroups. The analysis revealed that allele G of the investigated polymorphism in obese women with endometrial cancer is significantly more frequent, and allele T is significantly less frequent than in lean controls. However, no significant correlation was observed between the polymorphism and endometrial cancer in lean and overweight females. Single nucleotide polymorphism +276G > T (rs1501299) in ADIPOQ may be considered to be a risk factor of endometrial cancer. Further research on SNP in EC is warranted to obtain more conclusive outcomes.

  10. Interaction between β-hexachlorocyclohexane and ADIPOQ genotypes contributes to the risk of type 2 diabetes mellitus in East Chinese adults

    PubMed Central

    Li, Shushu; Wang, Xichen; Yang, Lu; Yao, Shen; Zhang, Ruyang; Xiao, Xue; Zhang, Zhan; Wang, Li; Xu, Qiujin; Wang, Shou-Lin

    2016-01-01

    Growing evidence links environmental exposure to hexachlorocyclohexanes (HCHs) to the risk of type 2 diabetes mellitus (T2DM), and ADIPOQ that encodes adiponectin is considered as an important gene for T2DM. However, the role of ADIPOQ-HCH interaction on T2DM risk remains unclear. Thus, a paired case-control study was conducted in an East Chinese community. A total of 1446 subjects, including 723 cases and 723 controls matched on age, gender and residence, were enrolled, and 4 types of HCH isomers were measured in serum samples using GC-MS/MS. Additionally, 4 candidate ADIPOQ SNPs (rs182052, rs266729, rs6810075, and rs16861194) were genotyped by TaqMan assay, and plasma adiponectin was measured using ELISA. No associations between 4 SNPs and T2DM risk were found, but T2DM risk significantly increased with serum levels of β-HCH (P < 0.001). Furthermore, the synergistic interaction between β-HCH and rs182052 significantly increased T2DM risk (OR I-additive model = 2.20, OR I-recessive model = 2.13). Additionally, individuals carrying only rs182052 (A allele) with high levels of β-HCH had significant reduction in adiponectin levels (P = 0.016). These results indicate that the interaction between rs182052 and β-HCH might increase the risk of T2DM by jointly decreasing the adiponectin level and potentially trigger T2DM development. PMID:27883041

  11. ADIPOQ — EDRN Public Portal

    Cancer.gov

    From NCBI Gene: This gene is expressed in adipose tissue exclusively. It encodes a protein with similarity to collagens X and VIII and complement factor C1q. The encoded protein circulates in the plasma and is involved with metabolic and hormonal processes. Mutations in this gene are associated with adiponectin deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Apr 2010

  12. Circulating HMW adiponectin isoform is heritable and shares a common genetic background with insulin resistance in non diabetic White Caucasians from Italy: evidence from a family-based study

    PubMed Central

    Menzaghi, Claudia; Salvemini, Lucia; Paroni, Giulia; De Bonis, Concetta; Mangiacotti, Davide; Fini, Grazia; Doria, Alessandro; Di Paola, Rosa; Trischitta, Vincenzo

    2009-01-01

    Objective Reduced circulating adiponectin levels contribute to the etiology of insulin-resistance. Adiponectin circulates in three different isoforms: high (HMW), medium (MMW), and low (LMW) molecular weight. The genetics of adiponectin isoforms is mostly unknown. Our aim was to investigate whether and to which extent circulating adiponectin isoforms are heritable and whether they share common genetic backgrounds with insulin resistance-related traits. Methods In a family based sample of 640 non diabetic White Caucasians from Italy, serum adiponectin isoforms concentrations were measured by ELISA. Three SNPs in the ADIPOQ gene previously reported to affect total adiponectin levels (rs17300539, rs1501299 and rs677395) were genotyped. The heritability of adiponectin isoform levels was assessed by variance component analysis. A linear mixed effects model was used to test association between SNPs and adiponectin isoforms. Bivariate analyses were conducted to study genetic correlations between adiponectin isoforms levels and other insulin resistance-related traits. Results All isoforms were highly heritable (h2=0.60−0.80, p=1×10−13–1×10−23). SNPs rs17300539, rs1501299 and rs6773957 explained a significant proportion of HMW variance (2–9%, p=1×10−3–1×10−5). In a multiple-SNP model, only rs17300539 and rs1501299 remained associated with HMW adiponectin (p=3×10−4 and 2.0×10−2). Significant genetic correlations (p=1×10−2–1×10−5) were observed between HMW adiponectin and fasting insulin, HOMAIR, HDL-cholesterol and the metabolic syndrome score. Only rs1501299 partly accounted for these genetic correlations. Conclusion Circulating levels of adiponectin isoforms are highly heritable. The genetic control of HMW adiponectin is shared in part with insulin resistance-related traits and involves, but is not limited to the ADIPOQ locus. PMID:19761474

  13. Induction of human adiponectin gene transcription by telmisartan, angiotensin receptor blocker, independently on PPAR-{gamma} activation

    SciTech Connect

    Moriuchi, Akie ||. E-mail: f1195@cc.nagasaki-u-ac.jp; Shimamura, Mika; Kita, Atsushi; Kuwahara, Hironaga; Satoh, Tsuyoshi; Satoh, Tsuyoshi; Fujishima, Keiichiro; Fukushima, Keiko |; Hayakawa, Takao; Mizuguchi, Hiroyuki; Nagayama, Yuji; Kawasaki, Eiji

    2007-05-18

    Adiponectin, an adipose tissue-specific plasma protein, has been shown to ameliorate insulin resistance and inhibit the process of atherosclerosis. Recently, several reports have stated that angiotensin type 1 receptor blockers (ARBs), increase adiponectin plasma level, and ameliorate insulin resistance. Telmisartan, a subclass of ARBs, has been shown to be a partial agonist of the peroxisome proliferator-activated receptor (PPAR)-{gamma}, and to increase the plasma adiponectin level. However, the transcriptional regulation of the human adiponectin gene by telmisartan has not been determined yet. To elucidate the effect of telmisartan on adiponectin, the stimulatory regulation of human adiponectin gene by telmisartan was investigated in 3T3-L1 adipocytes, utilizing adenovirus-mediated luciferase reporter gene-transferring technique. This study indicates that telmisartan may stimulate adiponectin transcription independent of PPAR-{gamma}.

  14. 4-Hydroxynonenal differentially regulates adiponectin gene expression and secretion via activating PPARγ and accelerating ubiquitin–proteasome degradation

    PubMed Central

    Wanga, Zhigang; Dou, Xiaobing; Gu, Dongfang; Shen, Chen; Yao, Tong; Nguyen, Van; Braunschweig, Carol; Song, Zhenyuan

    2011-01-01

    Although well-established, the underlying mechanisms involved in obesity-related plasma adiponectin decline remain elusive. Oxidative stress is associated with obesity and insulin resistance and considered to contribute to the progression toward obesity-related metabolic disorders. In this study, we investigated the effects of 4-hydroxynonenal (4-HNE), the most abundant lipid peroxidation end product, on adiponectin production and its potential implication in obesity-related adiponectin decrease. Long-term high-fat diet feeding led to obesity in mouse, accompanied by decreased plasma adiponectin and increased adipose tissue 4-HNE content. Exposure of adipocytes to exogenous 4-HNE resulted in decreased adiponectin secretion in a dose-dependent manner, which was consistent with significantly decreased intracellular adiponectin protein abundance. In contrast, adiponectin gene expression was significantly elevated by 4-HNE treatment, which was concomitant with increased peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression and transactivity. The effect was abolished by T0070907, a PPAR-γ antagonist, suggesting that PPAR-γ activation plays a critical role in this process. To gain insight into mechanisms involved in adiponectin protein decrease, we examined the effects of 4-HNE on adiponectin protein degradation. Cycloheximide (CHX)-chase assay revealed that 4-HNE exposure accelerated adiponectin protein degradation, which was prevented by MG132, a potent proteasome inhibitor. Immunoprecipitation assay showed that 4-HNE exposure increased ubiquitinated adiponectin protein levels. These data altogether indicated that 4-HNE enhanced adiponectin protein degradation via ubiquitin–proteasome system. Finally, we demonstrated that supplementation of HF diet with betaine, an antioxidant and methyl donor, alleviated high-fat-induced adipose tissue 4-HNE increase and attenuated plasma adiponectin decline. Taken together, our findings suggest that the lipid

  15. Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism.

    PubMed

    Liu, Qingqing; Yuan, Bingbing; Lo, Kinyui Alice; Patterson, Heide Christine; Sun, Yutong; Lodish, Harvey F

    2012-09-04

    The effects of adiponectin on hepatic glucose and lipid metabolism at transcriptional level are largely unknown. We profiled hepatic gene expression in adiponectin knockout (KO) and wild-type (WT) mice by RNA sequencing. Compared with WT mice, adiponectin KO mice fed a chow diet exhibited decreased mRNA expression of rate-limiting enzymes in several important glucose and lipid metabolic pathways, including glycolysis, tricarboxylic acid cycle, fatty-acid activation and synthesis, triglyceride synthesis, and cholesterol synthesis. In addition, binding of the transcription factor Hnf4a to DNAs encoding several key metabolic enzymes was reduced in KO mice, suggesting that adiponectin might regulate hepatic gene expression via Hnf4a. Phenotypically, adiponectin KO mice possessed smaller epididymal fat pads and showed reduced body weight compared with WT mice. When fed a high-fat diet, adiponectin KO mice showed significantly reduced lipid accumulation in the liver. These lipogenic defects are consistent with the down-regulation of lipogenic genes in the KO mice.

  16. Adiponectin pathway polymorphisms and risk of breast cancer in African Americans and Hispanics in the Women's Health Initiative.

    PubMed

    Kaklamani, Virginia G; Hoffmann, Thomas J; Thornton, Timothy A; Hayes, Geoffrey; Chlebowski, Rowan; Van Horn, Linda; Mantzoros, Christos

    2013-06-01

    Adiponectin, a protein secreted by the adipose tissue, is an endogenous insulin sensitizer with circulating levels that are decreased in obese and diabetic subjects. Recently, circulating levels of adiponectin have been correlated with breast cancer risk. Our previous work showed that polymorphisms of the adiponectin pathway are associated with breast cancer risk. We conducted the first study of adiponectin pathways in African Americans and Hispanics in the Women's Health Initiative SNP Health Association Resource cohort of 3,642 self-identified Hispanic women and 8,515 self-identified African American women who provided consent for DNA analysis. Single nucleotide polymorphisms (SNPs) from three genes were included in this analysis: ADIPOQ, ADIPOR1, and ADIPOR2. The genome-wide human SNP array 6.0 (909,622 SNPs) ( www.affymetrix.com ) was used. We found that rs1501299, a functional SNP of ADIPOQ that we previously reported was associated with breast cancer risk in a mostly Caucasian population, was also significantly associated with breast cancer incidence (HR for the GG/TG genotype: 1.23; 95 % CI 1.059-1.43) in African American women. We did not find any other SNPs in these genes to be associated with breast cancer incidence. This is the first study assessing the role of adiponectin pathway SNPs in breast cancer risk in African Americans and Hispanics. RS1501299 is significantly associated with breast cancer risk in African American women. As the rates of obesity and diabetes increase in African Americans and Hispanics, adiponectin and its functional SNPs may aid in breast cancer risk assessment.

  17. Association of adiponectin gene polymorphism 45TG with gestational diabetes mellitus diagnosed on the new IADPSG criteria, plasma adiponectin levels and adverse pregnancy outcomes.

    PubMed

    Han, Yun; Zheng, Yan-li; Fan, Yu-ping; Liu, Man-hua; Lu, Xiao-yan; Tao, Qian

    2015-02-01

    The aim of this study was to identify the association of adiponectin gene single nucleotide polymorphism (SNP) 45TG with gestational diabetes mellitus (GDM) diagnosed on the new International Diabetes in Pregnancy Consensus Group (IADPSG) criteria, plasma adiponectin levels and adverse pregnancy outcomes in Han women of Nantong area in China. This cross-sectional study included 128 pregnant women with GDM (GDM group) and 140 pregnant women with normal glucose tolerance (NGT group) according to oral glucose tolerance test results based on the new IADPSG criteria. The GDM pregnant women were treated by diet control or diet control and insulin injection. All pregnant women attended antenatal cares and were recorded until delivery. Adiponectin gene was amplified through PCR, and SNP was detected using restriction enzyme SmaI. Plasma adiponectin levels were measured by ELISA. The G allele and TG+GG genotype were significantly more frequent than the T allele in the GDM group than in the NGT group (p < 0.05). Plasma adiponectin concentrations of TG+GG genotype carriers were significantly lower than those of TT genotype in both groups (p < 0.01). After adjustment for confounding factors, plasma adiponectin level remained significantly lower in pregnant women with TG+GG genotype than those with TT genotype (p < 0.05). Compared with the NGT group, the GDM group with glycemic control still had significantly higher incidences of macrosomia, neonatal hypoglycemia and asphyxia (p < 0.05). Further analysis revealed that the incidences of macrosomia and neonatal hypoglycemia were significantly higher in pregnant women with TG+GG genotype than those with TT genotype after adjustment for potential confounders in affecting pregnancy outcomes (p < 0.05). Even though pregnant women are diagnosed as GDM according to the new IADPSG criteria, the adiponectin SNP45 may be closely correlated with the prevalence of GDM in Han women of Nantong area in China, and the allele +45G in adiponectin

  18. Genetic Architecture of Plasma Adiponectin Overlaps With the Genetics of Metabolic Syndrome–Related Traits

    PubMed Central

    Henneman, Peter; Aulchenko, Yurii S.; Frants, Rune R.; Zorkoltseva, Irina V.; Zillikens, M. Carola; Frolich, Marijke; Oostra, Ben A.; van Dijk, Ko Willems; van Duijn, Cornelia M.

    2010-01-01

    OBJECTIVE Adiponectin, a hormone secreted by adipose tissue, is of particular interest in metabolic syndrome, because it is inversely correlated with obesity and insulin sensitivity. However, it is not known to what extent the genetics of plasma adiponectin and the genetics of obesity and insulin sensitivity are interrelated. We aimed to evaluate the heritability of plasma adiponectin and its genetic correlation with the metabolic syndrome and metabolic syndrome–related traits and the association between these traits and 10 ADIPOQ single nucleotide polymorphisms (SNPs). RESEARCH DESIGN AND METHODS We made use of a family-based population, the Erasmus Rucphen Family study (1,258 women and 967 men). Heritability analysis was performed using a polygenic model. Genetic correlations were estimated using bivariate heritability analyses. Genetic association analysis was performed using a mixed model. RESULTS Plasma adiponectin showed a heritability of 55.1%. Genetic correlations between plasma adiponectin HDL cholesterol and plasma insulin ranged from 15 to 24% but were not significant for fasting glucose, triglycerides, blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR), and C-reactive protein. A significant association with plasma adiponectin was found for ADIPOQ variants rs17300539 and rs182052. A nominally significant association was found with plasma insulin and HOMA-IR and ADIPOQ variant rs17300539 after adjustment for plasma adiponectin. CONCLUSIONS The significant genetic correlation between plasma adiponectin and HDL cholesterol and plasma insulin should be taken into account in the interpretation of genome-wide association studies. Association of ADIPOQ SNPs with plasma adiponectin was replicated, and we showed association between one ADIPOQ SNP and plasma insulin and HOMA-IR. PMID:20067957

  19. Globular adiponectin enhances invasion in human breast cancer cells

    PubMed Central

    FALK LIBBY, EMILY; LIU, JIANZHONG; LI, YI; LEWIS, MONICA J.; DEMARK-WAHNEFRIED, WENDY; HURST, DOUGLAS R.

    2016-01-01

    Every year, a large number of women succumb to metastatic breast cancer due to a lack of curative approaches for this disease. Adiponectin (AdipoQ) is the most abundant of the adipocyte-secreted adipokines. In recent years, there has been an interest in the use of AdipoQ and AdipoQ receptor agonists as therapeutic agents for the treatment of breast cancer. However, while multiple epidemiological studies have previously indicated that low levels of circulating plasma AdipoQ portend poor prognosis in patients with breast cancer, recent studies have reported that elevated expression levels of AdipoQ in breast tissue are correlated with advanced stages of the disease. Thus, the aim of the present study was to clarify the mechanism by which AdipoQ in breast tissue acts directly on tumor cells to regulate the early steps of breast cancer metastasis. In the present study, the effects of different AdipoQ isoforms on the metastatic potential of human breast cancer cells were investigated. The results revealed that globular adiponectin (gAd) promoted invasive cell morphology and significantly increased the migration and invasion abilities of breast cancer cells, whereas full-length adiponectin (fAd) had no effect on these cells. Additionally, gAd, but not fAd, increased the expression levels of microtubule-associated protein 1 light chain 3 beta (LC3B)-II and intracellular LC3B puncta, which are indicators of autophagosome formation, thus suggesting autophagic induction by gAd. Furthermore, the inhibition of autophagic function by autophagy-related protein 7 knockdown attenuated the gAd-induced increase in invasiveness in breast cancer cells. Therefore, the results of the present study suggested that a specific AdipoQ isoform may enhance breast cancer invasion, possibly via autophagic induction. Understanding the roles of the different AdipoQ isoforms as microenvironmental regulatory molecules may aid the development of effective AdipoQ-based treatments for breast cancer

  20. Mendelian Randomization Studies Do Not Support a Causal Role for Reduced Circulating Adiponectin Levels in Insulin Resistance and Type 2 Diabetes

    PubMed Central

    Yaghootkar, Hanieh; Lamina, Claudia; Scott, Robert A.; Dastani, Zari; Hivert, Marie-France; Warren, Liling L.; Stancáková, Alena; Buxbaum, Sarah G.; Lyytikäinen, Leo-Pekka; Henneman, Peter; Wu, Ying; Cheung, Chloe Y.Y.; Pankow, James S.; Jackson, Anne U.; Gustafsson, Stefan; Zhao, Jing Hua; Ballantyne, Christie M.; Xie, Weijia; Bergman, Richard N.; Boehnke, Michael; el Bouazzaoui, Fatiha; Collins, Francis S.; Dunn, Sandra H.; Dupuis, Josee; Forouhi, Nita G.; Gillson, Christopher; Hattersley, Andrew T.; Hong, Jaeyoung; Kähönen, Mika; Kuusisto, Johanna; Kedenko, Lyudmyla; Kronenberg, Florian; Doria, Alessandro; Assimes, Themistocles L.; Ferrannini, Ele; Hansen, Torben; Hao, Ke; Häring, Hans; Knowles, Joshua W.; Lindgren, Cecilia M.; Nolan, John J.; Paananen, Jussi; Pedersen, Oluf; Quertermous, Thomas; Smith, Ulf; Lehtimäki, Terho; Liu, Ching-Ti; Loos, Ruth J.F.; McCarthy, Mark I.; Morris, Andrew D.; Vasan, Ramachandran S.; Spector, Tim D.; Teslovich, Tanya M.; Tuomilehto, Jaakko; van Dijk, Ko Willems; Viikari, Jorma S.; Zhu, Na; Langenberg, Claudia; Ingelsson, Erik; Semple, Robert K.; Sinaiko, Alan R.; Palmer, Colin N.A.; Walker, Mark; Lam, Karen S.L.; Paulweber, Bernhard; Mohlke, Karen L.; van Duijn, Cornelia; Raitakari, Olli T.; Bidulescu, Aurelian; Wareham, Nick J.; Laakso, Markku; Waterworth, Dawn M.; Lawlor, Debbie A.; Meigs, James B.; Richards, J. Brent; Frayling, Timothy M.

    2013-01-01

    Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics–based genetic risk scores to test the associations with gold-standard measures of insulin sensitivity (2,969 individuals) and type 2 diabetes (15,960 case subjects and 64,731 control subjects). In conventional regression analyses, a 1-SD decrease in adiponectin levels was correlated with a 0.31-SD (95% CI 0.26–0.35) increase in fasting insulin, a 0.34-SD (0.30–0.38) decrease in insulin sensitivity, and a type 2 diabetes odds ratio (OR) of 1.75 (1.47–2.13). The instrumental variable analysis revealed no evidence of a causal association between genetically lower circulating adiponectin and higher fasting insulin (0.02 SD; 95% CI −0.07 to 0.11; N = 29,771), nominal evidence of a causal relationship with lower insulin sensitivity (−0.20 SD; 95% CI −0.38 to −0.02; N = 1,860), and no evidence of a relationship with type 2 diabetes (OR 0.94; 95% CI 0.75–1.19; N = 2,777 case subjects and 13,011 control subjects). Using the ADIPOQ summary statistics genetic risk scores, we found no evidence of an association between adiponectin-lowering alleles and insulin sensitivity (effect per weighted adiponectin-lowering allele: −0.03 SD; 95% CI −0.07 to 0.01; N = 2,969) or type 2 diabetes (OR per weighted adiponectin-lowering allele: 0.99; 95% CI 0.95–1.04; 15,960 case subjects vs. 64,731 control subjects). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of

  1. Gene molecular analysis and Adiponectin expression in professional Water Polo players.

    PubMed

    Nigro, Ersilia; Sangiorgio, Dino; Scudiero, Olga; Monaco, Maria Ludovica; Polito, Rita; Villone, Giovanni; Daniele, Aurora

    2016-05-01

    Metabolic Syndrome prevalence has reaching epidemic proportions worldwide. Adiponectin (Acrp30), and in particular its High Molecular Weight (HMW) oligomers, contributes to enhance insulin sensitivity and to reduce inflammation levels. Physical exercise improves body's biochemical balance and metabolism resulting effective in prevention of metabolic diseases. Whether improvement of metabolic features mediated by physical exercise is associated with changes in Acrp30 serum composition is not yet clarified. In the present study, we investigated total Acrp30 expression, its oligomeric status and genetic variants in adiponectin gene (ACDC) in twenty-two professional Water Polo (WP) Players and 40 age- and sex-matched controls. Anthropometric, metabolic parameters and total Acrp30 were assessed; Acrp30 oligomeric profile was characterized by Western blot as well as by FPLC analysis. ACDC gene was analyzed by direct-sequencing analysis. Significant elevated body mass index, aspartate aminotransferase and lactate dehydrogenase levels and, conversely, significantly lower concentrations of total and cholesterol low density lipoprotein were present in WP players. No significant difference was found in total Acrp30 and/or HMW oligomers. Interestingly, in WP players, a direct relationship between total Acrp30 and monocytes as well as an inverse relationship between total Acrp30 and AST levels were found. ACDC screening revealed previously described SNPs. In conclusion, our study confirms the long-term beneficial effects of high physical training on metabolism and suggests that they are not associated with Acrp30 and/or HMW oligomers changes. Moreover, the correlation of Acrp30 with monocytes in WP athletes could represent a mechanism by which Acrp30 participates in exercise-induced anti-inflammatory functions and/or cardiovascular health.

  2. Adiponectin, a downstream target gene of peroxisome proliferator-activated receptor {gamma}, controls hepatitis B virus replication

    SciTech Connect

    Yoon, Sarah; Jung, Jaesung; Kim, Taeyeung; Park, Sun; Chwae, Yong-Joon; Shin, Ho-Joon; Kim, Kyongmin

    2011-01-20

    In this study, HepG2-hepatitis B virus (HBV)-stable cells that did not overexpress HBx and HBx-deficient mutant-transfected cells were analyzed for their expression of HBV-induced, upregulated adipogenic and lipogenic genes. The mRNAs of CCAAT enhancer binding protein {alpha} (C/EBP{alpha}), peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), adiponectin, liver X receptor {alpha} (LXR{alpha}), sterol regulatory element binding protein 1c (SREBP1c), and fatty acid synthase (FAS) were expressed at higher levels in HepG2-HBV and lamivudine-treated stable cells and HBx-deficient mutant-transfected cells than in the HepG2 cells. Lamivudine treatment reduced the mRNA levels of PPAR{gamma} and C/EBP{alpha}. Conversely, HBV replication was upregulated by adiponectin and PPAR{gamma} agonist rosiglitazone treatments and was downregulated by adiponectin siRNAs. Collectively, our results demonstrate that HBV replication and/or protein expression, even in the absence of HBx, upregulated adipogenic or lipogenic genes, and that the control of adiponectin might prove useful as a therapeutic modality for the treatment of chronic hepatitis B.

  3. Common genetic variation in adiponectin, leptin, and leptin receptor and association with breast cancer subtypes.

    PubMed

    Nyante, Sarah J; Gammon, Marilie D; Kaufman, Jay S; Bensen, Jeannette T; Lin, Dan Yu; Barnholtz-Sloan, Jill S; Hu, Yijuan; He, Qianchuan; Luo, Jingchun; Millikan, Robert C

    2011-09-01

    Adipocytokines are produced by visceral fat, and levels may be associated with breast cancer risk. We investigated whether single nucleotide polymorphisms (SNPs) in adipocytokine genes adiponectin (ADIPOQ), leptin (LEP), and the leptin receptor (LEPR) were associated with basal-like or luminal A breast cancer subtypes. 104 candidate and tag SNPs were genotyped in 1776 of 2022 controls and 1972 (200 basal-like, 679 luminal A) of 2311 cases from the Carolina Breast Cancer Study (CBCS), a population-based case-control study of whites and African Americans. Breast cancer molecular subtypes were determined by immunohistochemistry. Genotype odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Haplotype ORs and 95% CIs were estimated using Hapstat. Interactions with waist-hip ratio were evaluated using a multiplicative interaction term. Ancestry was estimated from 144 ancestry informative markers (AIMs), and included in models to control for population stratification. Candidate SNPs LEPR K109R (rs1137100) and LEPR Q223R (rs1137101) were positively associated with luminal A breast cancer, whereas ADIPOQ +45 T/G (rs2241766), ADIPOQ +276 G/T (rs1501299), and LEPR K656N (rs8129183) were not associated with either subtype. Few patterns were observed among tag SNPs, with the exception of 3 LEPR SNPs (rs17412175, rs9436746, and rs9436748) that were in moderate LD and inversely associated with basal-like breast cancer. However, no SNP associations were statistically significant after adjustment for multiple comparisons. Haplotypes in LEP and LEPR were associated with both basal-like and luminal A subtypes. There was no evidence of interaction with waist-hip ratio. Data suggest associations between LEPR candidate SNPs and luminal A breast cancer in the CBCS and LEPR intron 2 tag SNPs and basal-like breast cancer. Replication in additional studies where breast cancer subtypes have been defined is necessary to confirm these

  4. Common genetic variation in adiponectin, leptin, and leptin receptor and association with breast cancer subtypes

    PubMed Central

    Nyante, Sarah J.; Gammon, Marilie D.; Kaufman, Jay S.; Bensen, Jeannette T.; Lin, Dan Yu; Barnholtz-Sloan, Jill S.; Hu, Yijuan; He, Qianchuan; Luo, Jingchun; Millikan, Robert C.

    2012-01-01

    Adipocytokines are produced by visceral fat, and levels may be associated with breast cancer risk. We investigated whether single nucleotide polymorphisms (SNPs) in adipocytokine genes adiponectin (ADIPOQ), leptin (LEP), and the leptin receptor (LEPR) were associated with basal-like or luminal A breast cancer subtypes. 104 candidate and tag SNPs were genotyped in 1776 of 2022 controls and 1972 (200 basal-like, 679 luminal A) of 2311 cases from the Carolina Breast Cancer Study (CBCS), a population-based case–control study of whites and African Americans. Breast cancer molecular subtypes were determined by immunohistochemistry. Genotype odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Haplotype ORs and 95% CIs were estimated using Hapstat. Interactions with waist-hip ratio were evaluated using a multiplicative interaction term. Ancestry was estimated from 144 ancestry informative markers (AIMs), and included in models to control for population stratification. Candidate SNPs LEPR K109R (rs1137100) and LEPR Q223R (rs1137101) were positively associated with luminal A breast cancer, whereas ADIPOQ +45 T/G (rs2241766), ADIPOQ +276 G/T (rs1501299), and LEPR K656N (rs8129183) were not associated with either subtype. Few patterns were observed among tag SNPs, with the exception of 3 LEPR SNPs (rs17412175, rs9436746, and rs9436748) that were in moderate LD and inversely associated with basal-like breast cancer. However, no SNP associations were statistically significant after adjustment for multiple comparisons. Haplotypes in LEP and LEPR were associated with both basal-like and luminal A subtypes. There was no evidence of interaction with waist-hip ratio. Data suggest associations between LEPR candidate SNPs and luminal A breast cancer in the CBCS and LEPR intron 2 tag SNPs and basal-like breast cancer. Replication in additional studies where breast cancer subtypes have been defined is necessary to confirm these

  5. Dual matrilineal geographic distribution of Korean type 2 diabetes mellitus-associated -11,377 G adiponectin allele.

    PubMed

    Choi, Jee-Hye; Min, Na Young; Park, Sang Kil; Gavaachimed, Lkhagvasuren; Ko, Young Jong; Han, Sung Hoon; Kim, Kyung Yong; Kim, Kijung; Lee, Kwang Ho; Park, Ae Ja

    2014-12-01

    The present study was performed to identify the susceptible single nucleotide polymorphisms (SNPs) for the prediction of Korean type 2 diabetes mellitus (T2DM) and to clarify the matrilineal origin of Korean T2DM‑specific SNPs. Fourteen SNPs from the adiponectin (ADIPOQ), hepatocyte nuclear factor 4α, phosphoenolpyruvate carboxykinase 1 and glucokinase genes in the Korean population were analyzed. Only one SNP, ‑11,377 C/G on the ADIPOQ gene, was finally determined to be responsible for the incidence of Korean T2DM (P=0.028). The G‑T‑T‑A haplotype at positions ‑11,377, +45, +276 and +349 on the ADIPOQ gene was also associated with a high incidence of Korean T2DM (P=0.023). In addition, the susceptibility of Korean individuals to T2DM appears to be affected by their matrilineal origin. Of note, the group of Southern origin, consisting of mitochondrial DNA macrohaplogroups F and R, was predisposed to T2DM, whereas the group of Northern origin, consisting of haplogroups A and Y, was resistant to T2DM. This implied that the differential genetics between the two groups, which were formed from the initial peopling of the proto‑Korean population via Southern and Northern routes to the present time, may explain their differing susceptibility to T2DM. In conclusion, from Southern Asia Northward, a matrilineal origin of Korean individuals appears to be responsible for the prevalence of Korean T2DM caused by the ‑11,377 G allele.

  6. Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts

    SciTech Connect

    Kitahara, Kanako; Kusunoki, Natsuko; Kakiuchi, Terutaka; Suguro, Toru; Kawai, Shinichi

    2009-01-09

    The adipokines are linked not only to metabolic regulation, but also to immune responses. Adiponectin, but not leptin or resistin induced interleukin-8 production from rheumatoid synovial fibroblasts (RSF). The culture supernatant of RSF treated with adiponectin induced chemotaxis, although adiponectin itself had no such effect. Addition of antibody against adiponectin, and inhibition of adiponectin receptor gene decreased adiponectin-induced IL-8 production. Nuclear translocation of nuclear factor-kappa B was increased by adiponectin. The induction of interleukin-8 was inhibited by mitogen-activated protein kinase inhibitors. These findings suggest that adiponectin contributes to the pathogenesis of rheumatoid arthritis.

  7. Molecular characterization of an adiponectin receptor homolog in the white leg shrimp, Litopenaeus vannamei

    PubMed Central

    Kim, Ah Ran; Alam, Md Jobaidul; Yoon, Tae-ho; Lee, Soo Rin; Park, Hyun; Kim, Doo-Nam; An, Doo-Hae; Lee, Jae-Bong; Lee, Chung Il

    2016-01-01

    Adiponectin (AdipoQ) and its receptors (AdipoRs) are strongly related to growth and development of skeletal muscle, as well as glucose and lipid metabolism in vertebrates. Herein we report the identification of the first full-length cDNA encoding an AdipoR homolog (Liv-AdipoR) from the decapod crustacean Litopenaeus vannamei using a combination of next generation sequencing (NGS) technology and bioinformatics analysis. The full-length Liv-AdipoR (1,245 bp) encoded a protein that exhibited the canonical seven transmembrane domains (7TMs) and the inversed topology that characterize members of the progestin and adipoQ receptor (PAQR) family. Based on the obtained sequence information, only a single orthologous AdipoR gene appears to exist in arthropods, whereas two paralogs, AdipoR1 and AdipoR2, have evolved in vertebrates. Transcriptional analysis suggested that the single Liv-AdipoR gene appears to serve the functions of two mammalian AdipoRs. At 72 h after injection of 50 pmol Liv-AdipoR dsRNA (340 bp) into L. vannamei thoracic muscle and deep abdominal muscle, transcription levels of Liv-AdipoR decreased by 93% and 97%, respectively. This confirmed optimal conditions for RNAi of Liv-AdipoR. Knockdown of Liv-AdipoR resulted in significant changes in the plasma levels of ammonia, 3-methylhistine, and ornithine, but not plasma glucose, suggesting that that Liv-AdipoR is important for maintaining muscle fibers. The chronic effect of Liv-AdipoR dsRNA injection was increased mortality. Transcriptomic analysis showed that 804 contigs were upregulated and 212 contigs were downregulated by the knockdown of Liv-AdipoR in deep abdominal muscle. The significantly upregulated genes were categorized as four main functional groups: RNA-editing and transcriptional regulators, molecular chaperones, metabolic regulators, and channel proteins. PMID:27478708

  8. Molecular characterization of an adiponectin receptor homolog in the white leg shrimp, Litopenaeus vannamei.

    PubMed

    Kim, Ah Ran; Alam, Md Jobaidul; Yoon, Tae-Ho; Lee, Soo Rin; Park, Hyun; Kim, Doo-Nam; An, Doo-Hae; Lee, Jae-Bong; Lee, Chung Il; Kim, Hyun-Woo

    2016-01-01

    Adiponectin (AdipoQ) and its receptors (AdipoRs) are strongly related to growth and development of skeletal muscle, as well as glucose and lipid metabolism in vertebrates. Herein we report the identification of the first full-length cDNA encoding an AdipoR homolog (Liv-AdipoR) from the decapod crustacean Litopenaeus vannamei using a combination of next generation sequencing (NGS) technology and bioinformatics analysis. The full-length Liv-AdipoR (1,245 bp) encoded a protein that exhibited the canonical seven transmembrane domains (7TMs) and the inversed topology that characterize members of the progestin and adipoQ receptor (PAQR) family. Based on the obtained sequence information, only a single orthologous AdipoR gene appears to exist in arthropods, whereas two paralogs, AdipoR1 and AdipoR2, have evolved in vertebrates. Transcriptional analysis suggested that the single Liv-AdipoR gene appears to serve the functions of two mammalian AdipoRs. At 72 h after injection of 50 pmol Liv-AdipoR dsRNA (340 bp) into L. vannamei thoracic muscle and deep abdominal muscle, transcription levels of Liv-AdipoR decreased by 93% and 97%, respectively. This confirmed optimal conditions for RNAi of Liv-AdipoR. Knockdown of Liv-AdipoR resulted in significant changes in the plasma levels of ammonia, 3-methylhistine, and ornithine, but not plasma glucose, suggesting that that Liv-AdipoR is important for maintaining muscle fibers. The chronic effect of Liv-AdipoR dsRNA injection was increased mortality. Transcriptomic analysis showed that 804 contigs were upregulated and 212 contigs were downregulated by the knockdown of Liv-AdipoR in deep abdominal muscle. The significantly upregulated genes were categorized as four main functional groups: RNA-editing and transcriptional regulators, molecular chaperones, metabolic regulators, and channel proteins.

  9. Association of Single Nucleotide Polymorphisms of Adiponectin Gene with Type 2 Diabetes Mellitus, and Their Influence on Cardiovascular Risk Markers.

    PubMed

    Momin, A A; Bankar, M P; Bhoite, G M

    2017-03-01

    Type 2 diabetes mellitus is a genetically heterogeneous condition, characterized by insulin deficiency and/or insulin resistance. The etiology of type 2 diabetes is complex, with involvement of genetic and environmental factors. The adipose tissue protein 'adiponectin' is known to increase insulin sensitivity with decreased risk of type 2 diabetes mellitus. The gene for adiponectin is present on chromosome 3q27, the association of number of single nucleotide polymorphisms of adiponectin gene with type 2 diabetes and its complications have been reported. In the present study the two most common SNPs +45T/G & +276G/T, and their association with type 2 diabetes mellitus and cardiovascular markers were studied. The significant difference in genotype frequencies of +45T/G & +276G/T was found in type 2 diabetic patients and controls, with odds ratio of 1.13 & 1.26 respectively. BMI, Fasting blood glucose, fasting insulin, HOMA IR, triglyceride and VLDL cholesterol levels were increased, and HDL cholesterol level was decreased in patients carrier for +45T/G SNP than the wild type. While only decrease in the HDL cholesterol was reported in carriers for SNP +276G/T than the wild type. The logistic regression analysis revealed the positive association of SNP +45T/G with total cholesterol & LDL cholesterol. And negative association of HDL cholesterol was found with SNPs +45T/G and +276G/T. The haplotype analysis shows the alterations in means of biochemical markers in the patients having haplotype (GG) for mutant allele of SNP +45T/G and wild allele for SNP +276G/T.

  10. Bayesian analysis of genetic interactions in case-control studies, with application to adiponectin genes and colorectal cancer risk.

    PubMed

    Yi, Nengjun; Kaklamani, Virginia G; Pasche, Boris

    2011-01-01

    Complex diseases such as cancers are influenced by interacting networks of genetic and environmental factors. However, a joint analysis of multiple genes and environmental factors is challenging, owing to potentially large numbers of correlated and complex variables. We describe Bayesian generalized linear models for simultaneously analyzing covariates, main effects of numerous loci, gene-gene and gene-environment interactions in population case-control studies. Our Bayesian models use Student-t prior distributions with different shrinkage parameters for different types of effects, allowing reliable estimates of main effects and interactions and hence increasing the power for detection of real signals. We implement a fast and stable algorithm for fitting models by extending available tools for classical generalized linear models to the Bayesian case. We propose a novel method to interpret and visualize models with multiple interactions by computing the average predictive probability. Simulations show that the method has the potential to dissect interacting networks of complex diseases. Application of the method to a large case-control study of adiponectin genes and colorectal cancer risk highlights the previous results and detects new epistatic interactions and sex-specific effects that warrant follow-up in independent studies.

  11. Adiponectin Enhances Mouse Fetal Fat Deposition

    PubMed Central

    Qiao, Liping; Yoo, Hyung sun; Madon, Alysha; Kinney, Brice; Hay, William W.; Shao, Jianhua

    2012-01-01

    Maternal obesity increases offspring birth weight and susceptibility to obesity. Adiponectin is an adipocyte-secreted hormone with a prominent function in maintaining energy homeostasis. In contrast to adults, neonatal blood adiponectin levels are positively correlated with anthropometric parameters of adiposity. This study was designed to investigate the role of adiponectin in maternal obesityenhanced fetal fat deposition. By using high-fat diet–induced obese mouse models, our study showed that maternal obesity increased fetal fat tissue mass, with a significant elevation in fetal blood adiponectin. However, adiponectin gene knockout (Adipoq−/−) attenuated maternal obesity-induced high fetal fat tissue mass. We further studied the effects of fetal adiponectin on fetal fat deposition by using a cross breeding approach to create Adipoq−/+ and Adipoq−/− offspring, whereas maternal adiponectin was null. Adipoq−/+ offspring had more fat tissue mass at both birth and adulthood. Significantly high levels of lipogenic genes, such as sterol regulatory element–binding protein 1c and fatty acid synthase, were detected in the livers of Adipoq−/+ fetuses. In addition, expression of genes for placental fatty acid transport was significantly increased in Adipoq−/+ fetuses. Together, our study indicates that adiponectin enhances fetal fat deposition and plays an important role in maternal obesity-induced high birth weight. PMID:22872236

  12. Construction of adiponectin-encoding plasmid DNA and gene therapy of non-obese type 2 diabetes mellitus.

    PubMed

    Nan, Mei Hua; Park, Jeong-Sook; Myung, Chang-Seon

    2010-01-01

    Adiponectin (ADN), an insulin-sensitizing adipokine, stimulates glucose uptake, inhibits gluconeogenesis, and plays an important role in improving insulin sensitivity. Since blood levels of ADN are low in type 2 diabetes mellitus (DM), this study was designed to investigate the therapeutic effectiveness of increasing the ADN level through injection of plasmid DNA encoding ADN in type 2 DM. A non-obese type 2 DM mouse model was established via combined administration of streptozotocin with nicotinamide and exhibited significantly higher plasma glucose concentration and insulin resistance compared with normal controls according to oral glucose tolerance and insulin challenge tests. Plasmid DNA encoding mouse ADN from differentiated NIH3T3 adipocytes was constructed in pVAX1 (pVAX/ADN). Transfection of pVAX/ADN into various cell lines including HeLa, HT22, HEK293, HepG2, and SK-Hep1 cells, increased ADN mRNA expression levels in a dose-dependent manner. The administration of pVAX/ADN into non-obese type 2 DM mice via tail vein significantly increased the blood level of ADN and decreased the plasma glucose concentration. Moreover, the parameters related to insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) were significantly improved. These results suggest that ADN gene therapy could be a clinically effective tool for the treatment of type 2 DM.

  13. Impacts of Nonsynonymous Single Nucleotide Polymorphisms of Adiponectin Receptor 1 Gene on Corresponding Protein Stability: A Computational Approach

    PubMed Central

    Saleh, Md. Abu; Solayman, Md.; Paul, Sudip; Saha, Moumoni; Khalil, Md. Ibrahim; Gan, Siew Hua

    2016-01-01

    Despite the reported association of adiponectin receptor 1 (ADIPOR1) gene mutations with vulnerability to several human metabolic diseases, there is lack of computational analysis on the functional and structural impacts of single nucleotide polymorphisms (SNPs) of the human ADIPOR1 at protein level. Therefore, sequence- and structure-based computational tools were employed in this study to functionally and structurally characterize the coding nsSNPs of ADIPOR1 gene listed in the dbSNP database. Our in silico analysis by SIFT, nsSNPAnalyzer, PolyPhen-2, Fathmm, I-Mutant 2.0, SNPs&GO, PhD-SNP, PANTHER, and SNPeffect tools identified the nsSNPs with distorting functional impacts, namely, rs765425383 (A348G), rs752071352 (H341Y), rs759555652 (R324L), rs200326086 (L224F), and rs766267373 (L143P) from 74 nsSNPs of ADIPOR1 gene. Finally the aforementioned five deleterious nsSNPs were introduced using Swiss-PDB Viewer package within the X-ray crystal structure of ADIPOR1 protein, and changes in free energy for these mutations were computed. Although increased free energy was observed for all the mutants, the nsSNP H341Y caused the highest energy increase amongst all. RMSD and TM scores predicted that mutants were structurally similar to wild type protein. Our analyses suggested that the aforementioned variants especially H341Y could directly or indirectly destabilize the amino acid interactions and hydrogen bonding networks of ADIPOR1. PMID:27294143

  14. The Relationship between Adiponectin and Breast Cancer

    PubMed Central

    Erbay, Burcu; Yılmaz, Tonguç Utku; Eraldemir, Ceyla; Üren, Nihal; Tiryaki, Çağrı; Ergül, Emel; Utkan, Zafer

    2016-01-01

    Objective Breast cancer is the most common type of cancer in women worldwide. It is indicated that increased body mass index elevates the risk of developing breast cancer, worsens prognosis, and decreases survival. Several polymorphisms of adiponectin have been shown to affect serum levels of adiponectin and their association with breast cancer. The aim of this study was to investigate the relationship between the adiponectin 45T/G and 276 G/T gene polymorphism and breast cancer in the East Marmara region. Materials and Methods A case-control study was performed in 97 patients with breast cancer and 101 controls in East Marmara in order to evaluate the prevalence of adiponectin gene polymorphism at positions 45 and 276. Patients with familial breast cancer and those who had received chemotherapy or radiotherapy were excluded from the study. Adiponectin gene polymorphisms were investigated using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). Results Adiponectin 45T/G gene genotype frequencies of TT, TG, and GG were 61.9%, 37.1%, and 1% in patients with breast cancer, and 67.3%, 30.7%, and 2% in the control group, respectively. Adiponectin 276G/T gene genotype frequencies of GG, GT, and TT were 45.4%, 45.4%, and 9.3% in patients with breast cancer and 55.4%, 39.6%, and 5.0% in the control group, respectively. Conclusion Our study showed that adiponectin 45T/G and 276 G/T gene polymorphism is not associated with breast cancer risk in patients from the East Marmara region.

  15. Adiponectin and colorectal cancer.

    PubMed

    Otani, Kensuke; Ishihara, Soichiro; Yamaguchi, Hironori; Murono, Koji; Yasuda, Koji; Nishikawa, Takeshi; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Kawai, Kazushige; Nozawa, Hiroaki; Watanabe, Toshiaki

    2017-02-01

    Colorectal cancer is an obesity-related malignancy. Adiponectin is an adipokine produced exclusively by adipose tissue, and its concentration in the serum is reduced in obesity. A low serum level of adiponectin is associated with an increased risk of various types of malignancies including colorectal cancer. These facts suggest that the epidemiological link between obesity and cancer may have a significant association with adiponectin. Although numerous studies of colorectal cancer have been reported, the results are conflicting about the anti-cancer effect of adiponectin, and how adiponectin affects carcinogenesis or cancer development remains controversial. Because adiponectin has multiple systemic effects and exists as a high serum concentration protein, the main role of adiponectin should be regulation of homeostasis, and it would not likely act as an anti-cancerous hormone. However, as epidemiological evidence shows, a low adiponectin level may be a basic risk factor for colorectal cancer. We speculate that when the colonic epithelium is stimulated or damaged by another carcinogen under the condition of a low adiponectin level, carcinogenesis is promoted and cancer development is facilitated. In this report, we summarize recent findings of the correlation between adiponectin and colorectal cancer and investigate the effect of adiponectin on colorectal cancer.

  16. Changes in adiponectin and inflammatory genes in response to hormonal imbalances in female mice and exacerbation of depot selective visceral adiposity by high-fat diet: implications for insulin resistance.

    PubMed

    Zhang, Hui; Chen, Xinlei; Aravindakshan, Jayaprakash; Sairam, M Ram

    2007-12-01

    Early obesity and late onset of insulin resistance associated with hormonal imbalances occur in FSH receptor-deficient follitropin receptor knockout female mice. This study tests the hypothesis that chronic high-fat diet aggravates obesogenic changes in a depot-specific manner and explores some molecular links of hormone imbalances with insulin resistance. In SV 129 mice, hormonal imbalances seem obligatory for exacerbation of diet-induced obesity. Visceral adiposity, glucose intolerance, and lipid disturbances in 9-month follitropin receptor knockout females were associated with decrease in adiponectin signaling. High-molecular-weight plasma adiponectin and adipose tissue adiponectin mRNA were decreased. Adiponectin receptors R1 and R2 mRNA was selectively altered in mesenteric fat but not periuterine fat. R2 decreased in the liver and R1 was higher in muscle. Whereas hepatic adenosine monophosphate T-activated protein kinase activity was down-regulated, both phosphoenolpyruvate carboxykinase and glucose-6-phosphatase enzymes were up-regulated. Longitudinally, diminishing sex hormone signaling in adipose tissue was associated with progressive down-regulation of adiponectin activity and gradual impaired glucose tolerance. Chronic high-fat diet in SV129 wild-type mice did not produce overt obesity but induced visceral fat depot changes accompanied by liver lipid accumulation, high cholesterol, and up-regulation of inflammation gene mRNAs. Thus, TNF-alpha, C-C motif chemokine receptor-2, and C-C motif chemokine ligand-2 were selectively elevated in mesenteric fat without altering glucose tolerance and adiponectin signaling. Our study highlights adiponectin signaling and regulation to be involved in hormone imbalance-induced insulin resistance and demonstrates selective visceral adipose depot alterations by chronic high-fat diet and induction of inflammatory genes.

  17. MRNA expression of genes regulating lipid metabolism in ringed seals (Pusa hispida) from differently polluted areas.

    PubMed

    Castelli, Martina Galatea; Rusten, Marte; Goksøyr, Anders; Routti, Heli

    2014-01-01

    There is a growing concern about the ability of persistent organic pollutants (POPs) to influence lipid metabolism. Although POPs are found at high concentrations in some populations of marine mammals, for example in the ringed seal (Pusa hispida) from the Baltic Sea, little is known about the effects of POPs on their lipid metabolism. An optimal regulation of lipid metabolism is crucial for ringed seals during the fasting/molting season. This is a physiologically stressful period, during which they rely on the energy stored in their fat reserves. The mRNA expression levels for seven genes involved in lipid metabolism were analyzed in liver and/or blubber tissue from molting ringed seals from the polluted Baltic Sea and a less polluted reference location, Svalbard (Norway). mRNA expression of genes encoding peroxisome proliferator-activated receptors (PPAR) α and γ and their target genes acyl-coenzyme A oxidase 1 (ACOX1) and cluster of differentiation 36 (CD36) were analyzed in liver. mRNA expression level of genes encoding PPARβ, PPARγ and their target genes encoding fatty acid binding protein 4 (FABP4) and adiponectin (ADIPOQ) were measured in inner and middle blubber layers. In addition, we evaluated the influence of molting status on hepatic mRNA expression of genes encoding PPARs and their target genes in ringed seals from Svalbard. Our results show higher mRNA expression of genes encoding hepatic PPARγ and adipose PPARβ, FABP4, and ADIPOQ in the Baltic seals compared to the Svalbard seals. A positive relationship between mRNA expressions of genes encoding hepatic PPARγ, adipose FABP4, adipose ADIPOQ and ΣPOP concentrations was observed. These findings suggest that lipid metabolism may be affected by contaminant exposure in the Baltic population. mRNA expression of genes encoding PPARβ, PPARγ, FABP4 and ADIPOQ were similar between the mid and inner adipose layer. Hepatic mRNA expression of genes encoding PPARα and PPARγ was higher in the pre

  18. Single nucleotide polymorphisms of metabolic syndrome-related genes in primary open angle glaucoma

    PubMed Central

    Zhou, Gang; Liu, Bin

    2010-01-01

    AIM To analyze single nucleotide polymorphisms (SNP) of primary open angle glaucoma- and metabolic syndrome-related genes in primary open angle glaucoma (POAG), in order to elucidate the roles of metabolic syndrome as a risk factor in POAG progress. METHODS SNP genotypes and alleles of interleukin-6 (IL-6), IL-6 receptor (IL-6R), dopamine D2 receptor (DRD2), beta-fibrinogen (FGB), peroxisome proliferator-activated receptor-γ2 (PPARG), transforming growth factor-β1 (TGF-β1), E-selectin (E-Sel), apolipoprotein A-5 (APOA5), C-reactive protein (CRP), ectonueleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), hepatic lipase (LIPC), adiponectin (ADIPOQ), paraoxonase 1 (PON1) and serine protease inhibitor E (SERPINE1) genes in POAG (n=37) and normal control (n=100) groups were measured with ABI Prism 7900HT Fluorescence Quantitative PCR and TaqMan SNP Genotyping fluorescence probe kit. RESULTS Genotypes and allele frequencies of IL-6R, IL-6, FGB, CRP, ENPP1, LIPC, ADIPOQ, PON1, and SERPINE1 in total POAG group were significantly different compared to the control group. CONCLUSION Metabolic syndrome as a risk factor for POAG may be associated with genotypes and allele frequencies of the related genes. The corresponding gene expression and function can affect POAG progress, including roles of SERPINE1 in extracellular matrix, ENPP1 in insulin inhibition, IL-6 in endogenous neuroprotection, IL-6, IL-6R and E-Sel in autoimmune response, LIPC and FGB in blood hyperviscosity syndrome, ADIPOQ in NOS/NO production, PON1 in vascular endothelial protection. PMID:22553514

  19. ADIPONECTIN IN SEVERE PREECLAMPSIA

    PubMed Central

    Nien, Jyh Kae; Mazaki-Tovi, Shali; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Gotsch, Francesca; Pineles, Beth L.; Gomez, Ricardo; Edwin, Samuel; Mazor, Moshe; Espinoza, Jimmy; Yoon, Bo Hyun; Hassan, Sonia S.

    2008-01-01

    Aims Adiponectin is an adipokine with insulin-sensitizing, anti-atherogenic, anti-inflammatory and angiogenic properties. The aims of this study were to determine whether maternal plasma adiponectin concentrations differ between patients with severe preeclampsia and those with normal pregnancies, and to explore the relationship between plasma adiponectin and the results of Doppler velocimetry of the uterine arteries. Methods This case-control study included two groups: (1) patients with severe preeclampsia (n=50) and (2) patients with normal pregnancies (n=150). Pulsed-wave and color Doppler ultrasound examination of the uterine arteries were performed. Plasma adiponectin concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results (1) Patients with severe preeclampsia had a higher median plasma concentration of adiponectin than that of normal pregnant women. (2) The median plasma adiponectin concentration did not differ between women with severe preeclampsia who had a high impedance to blood flow in the uterine arteries and those with normal impedance to blood flow. (3) Among patients with normal pregnancies, plasma adiponectin concentrations were negatively correlated with BMI in the first trimester and at sampling. Conclusions Women with severe preeclampsia have a higher median plasma concentration of adiponectin than that of normal pregnant women. This may reflect a compensatory feedback mechanism to the metabolically-altered, anti-angiogenic and pro-atherogenic state of severe preeclampsia. PMID:17919115

  20. Adiponectin inhibits Lrp6 phosphorylation and β-catenin signaling

    PubMed Central

    Reinke, Lauren; Lam, Anna P.; Flozak, Annette S.; Varga, John; Gottardi, Cara J.

    2016-01-01

    Adiponectin is a pleiotropic adipokine implicated in obesity, metabolic syndrome and cardiovascular disease. Recent studies have identified adiponectin as a negative regulator of tissue fibrosis. Wnt/β-catenin signaling has also been implicated in metabolic syndrome and can promote tissue fibrosis, but the extent to which adiponectin cross-regulates Wnt/β-catenin signaling is unknown. Using primary human dermal fibroblasts and recombinant purified proteins, we show that adiponectin can limit β-catenin accumulation and downstream gene activation by inhibiting Lrp6 phosphorylation, a key activation step in canonical Wnt signaling. Inhibition of Wnt3a-mediated Lrp6 phospho-activation is relatively rapid (e.g., by 30 minutes), and is not dependent on established adiponectin G-protein coupled receptors, AdipoR1 and R2, suggesting a more direct relationship to Lrp6 signaling. In contrast, the ability of adiponectin to limit Wnt-induced and baseline collagen production in fibroblasts requires AdipoR1/R2. These results suggest the possibility that the pleiotropic effects of adiponectin may be mediated through distinct cell surface receptor complexes. Accordingly, we propose that the anti-fibrotic activity of adiponectin may be mediated through AdipoR1/R2 receptors, while the ability of adiponectin to inhibit Lrp6 phospho-activation may be relevant to other recently established roles for Lrp6 signaling in glucose metabolism and metabolic syndrome. PMID:26797284

  1. Expression of adiponectin receptors in mouse adrenal glands and the adrenocortical Y-1 cell line: adiponectin regulates steroidogenesis.

    PubMed

    Li, Ping; Sun, Fei; Cao, Huang-Ming; Ma, Qin-Yun; Pan, Chun-Ming; Ma, Jun-Hua; Zhang, Xiao-Na; Jiang, He; Song, Huai-Dong; Chen, Ming-Dao

    2009-12-25

    Obesity is frequently associated with malfunctions of the hypothalamus-pituitary-adrenal (HPA) axis and hyperaldosteronism, but the mechanism underlying this association remains unclear. Since the adrenal glands are embedded in adipose tissue, direct cross-talk between adipose tissue and the adrenal gland has been proposed. A previous study found that adiponectin receptor mRNA was expressed in human adrenal glands and aldosterone-producing adenoma (APA). However, the expression of adiponectin receptors in adrenal glands has not been confirmed at the protein level or in other species. Furthermore, it is unclear whether adiponectin receptors expressed in adrenal cells are functional. We found, for the first time, that adiponectin receptor (AdipoR1 and AdipoR2) mRNA and protein were expressed in mouse adrenal and adrenocortical Y-1 cells. However, adiponectin itself was not expressed in mouse adrenal or Y-1 cells. Furthermore, adiponectin acutely reduced basal levels of corticosterone and aldosterone secretion. ACTH-induced steroid secretion was also inhibited by adiponectin, and this was accompanied by a parallel change in the expression of the key genes involved in steroidogenesis. These findings indicate that adiponectin may take part in the modulation of steroidogenesis. Thus, adiponectin is likely to have physiological and/or pathophysiological significance as an endocrine regulator of adrenocortical function.

  2. Association of Apolipoprotein B and Adiponectin Receptor 1 Genes with Carcass, Bone Integrity and Performance Traits in a Paternal Broiler Line

    PubMed Central

    da Cruz, Valdecy Aparecida Rocha; Schenkel, Flávio Schramm; Savegnago, Rodrigo Pelicioni; Grupioni, Natalia Vinhal; Stafuzza, Nedenia Bonvino; Sargolzaei, Mehdi; Ibelli, Adriana Mércia Guaratini; Peixoto, Jane de Oliveira; Ledur, Mônica Corrêa; Munari, Danísio Prado

    2015-01-01

    Apolipoprotein B (APOB) and Adiponectin Receptor 1 (ADIPOR1) are related to the regulation of feed intake, fat metabolism and protein deposition and are candidate genes for genomic studies in birds. In this study, associations of two single nucleotide polymorphisms (SNPs) g.102A>T (APOB) and g.729C>T (ADIPOR1) with carcass, bone integrity and performance traits in broilers were investigated. Genotyping was performed on a paternal line of 1,454 broilers. The SNP detection was carried out by PCR-RFLP technique using the restriction enzymes HhaI for the SNP g.729C>T and MslI for the SNP g.102A>T. The association analyses of the two SNPs with 85 traits were performed using the restricted maximum likelihood (REML) and Generalized Quasi-Likelihood Score (GQLS) methods. For REML the model included the random additive genetic effect of animal and fixed effects of sex, hatch and SNP genotypes. In the GQLS method, a logistic regression was used to associate the genotypes with phenotypes adjusted for fixed effects of sex and hatch. The SNP g.729C>T in the ADIPOR1 gene was associated with thickness of the femur and breast skin yield. Thus, the ADIPOR1 gene seems implicated in the metabolism and/or fat deposition and bone integrity in broilers. PMID:26322976

  3. Global Loss of Bmal1 Expression Alters Adipose Tissue Hormones, Gene Expression and Glucose Metabolism

    PubMed Central

    Kennaway, David John; Varcoe, Tamara Jayne; Voultsios, Athena; Boden, Michael James

    2013-01-01

    The close relationship between circadian rhythm disruption and poor metabolic status is becoming increasingly evident, but role of adipokines is poorly understood. Here we investigated adipocyte function and the metabolic status of mice with a global loss of the core clock gene Bmal1 fed either a normal or a high fat diet (22% by weight). Bmal1 null mice aged 2 months were killed across 24 hours and plasma adiponectin and leptin, and adipose tissue expression of Adipoq, Lep, Retn and Nampt mRNA measured. Glucose, insulin and pyruvate tolerance tests were conducted and the expression of liver glycolytic and gluconeogenic enzyme mRNA determined. Bmal1 null mice displayed a pattern of increased plasma adiponectin and plasma leptin concentrations on both control and high fat diets. Bmal1 null male and female mice displayed increased adiposity (1.8 fold and 2.3 fold respectively) on the normal diet, but the high fat diet did not exaggerate these differences. Despite normal glucose and insulin tolerance, Bmal1 null mice had increased production of glucose from pyruvate, implying increased liver gluconeogenesis. The Bmal1 null mice had arrhythmic clock gene expression in epigonadal fat and liver, and loss of rhythmic transcription of a range of metabolic genes. Furthermore, the expression of epigonadal fat Adipoq, Retn, Nampt, AdipoR1 and AdipoR2 and liver Pfkfb3 mRNA were down-regulated. These results show for the first time that global loss of Bmal1, and the consequent arrhythmicity, results in compensatory changes in adipokines involved in the cellular control of glucose metabolism. PMID:23750248

  4. Serum 25-Hydroxyvitamin D Levels, phosphoprotein enriched in diabetes gene product (PED/PEA-15) and leptin-to-adiponectin ratio in women with PCOS

    PubMed Central

    2011-01-01

    Background Polycystic ovary syndrome (PCOS) is frequently associated with hypovitaminosis D. Vitamin D is endowed with pleiotropic effects, including insulin resistance (IR) and apoptotic pathway. Disruption of the complex mechanism that regulated ovarian apoptosis has been reported in PCOS. Phosphoprotein enriched in diabetes gene product (PED/PEA-15), an anti-apoptotic protein involved in type 2 diabetes mellitus (T2DM), is overexpressed in PCOS women, independently of obesity. Leptin-to-adiponectin ratio (L/A) is a biomarker of IR and low-grade inflammation in PCOS. The aim of the study was to investigate the levels of 25-hydroxy vitamin D (25(OH)D), and L/A, in association with PED/PEA-15 protein abundance, in both lean and overweight/obese (o/o) women with PCOS. Patients and Methods PED/PEA-15 protein abundance and circulating levels of 25(OH)D, L/A, sex hormone-binding globulin, and testosterone were evaluated in 90 untreated PCOS patients (25 ± 4 yrs; range 18-34) and 40 healthy controls age and BMI comparable, from the same geographical area. FAI (free androgen index) and the homeostasis model assessment of insulin resistance (HoMA-IR) index were calculated. Results In o/o PCOS, 25(OH)D levels were significantly lower, and L/A values were significantly higher than in lean PCOS (p < 0.001), while there were no differences in PED/PEA-15 protein abundance. An inverse correlation was observed between 25(OH)D and BMI, PED/PEA-15 protein abundance, insulin, HoMA-IR, FAI (p < 0.001), and L/A (p < 0.05). At the multivariate analysis, in o/o PCOS L/A, insulin and 25(OH)D were the major determinant of PED/PEA-15 protein abundance (β = 0.45, β = 0.41, and β = -0.25, respectively). Conclusions Lower 25(OH)D and higher L/A were associated to PED/PEA-15 protein abundance in PCOS, suggesting their involvement in the ovarian imbalance between pro-and anti-apoptotic mechanisms, with high L/A and insulin and low 25(OH)D levels as the main determinants of PED/PEA-15

  5. [Adiponectin: an anti-carcinogenic adipokine?].

    PubMed

    Fève, Bruno

    2013-05-01

    Adipose tissue has long been considered as an « organ » of energy storage. Although many works had previously identified the secretory nature of adipocyte, it was only in 1994, when the leptin gene was cloned, that adipose tissue earned the status of endocrine tissue. It was the first demonstration that an adipose tissue-derived hormone was able to communicate with the central nervous system to control satiety and energy balance. In fact, it is almost at the same time that another major adipokine produced by adipocytes, adiponectin, has been discovered. It took several years to identify the insulin-sensitizing, anti-inflammatory and anti-atherogenic properties of this hormone. More recently, several epidemiological, genetic and experimental findings suggest an anti-carcinogenic role for adiponectin. In this brief review we will present the arguments supporting a protective role of adiponectin in tumor progression, particularly in the context of breast cancer. Adiponectin deficiency commonly observed in obesity may contribute to the natural history of several cancers, as well as the elevation of leptin and other hormonal disturbances associated with excessive adiposity.

  6. Adiponectin in mice with altered growth hormone action: links to insulin sensitivity and longevity?

    PubMed Central

    Lubbers, Ellen R.; List, Edward O.; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D.; Kineman, Rhonda D.; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J.; Berryman, Darlene E.

    2013-01-01

    Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high molecular weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered growth hormone (GH) signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH versus IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our results show that adiponectin is generally negatively associated with GH activity, regardless of age. Further, the amount of HMW adiponectin is consistently linked with the level of total adiponectin and not necessarily with previously reported lifespan or insulin sensitivity of these mice. Interestingly, circulating adiponectin levels correlated strongly with inguinal fat mass, implying the effects of GH on adiponectin are depot-specific. Interestingly rbGH, but not IGF1, decreased circulating total and HMW adiponectin levels. Taken together, these results fill important gaps in the literature related to GH and adiponectin and question the frequently reported associations of total and HMW adiponectin with insulin sensitivity and longevity. PMID:23261955

  7. Adiponectin in mice with altered GH action: links to insulin sensitivity and longevity?

    PubMed

    Lubbers, Ellen R; List, Edward O; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D; Kineman, Rhonda D; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J; Berryman, Darlene E

    2013-03-01

    Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high-molecular-weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered GH signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH vs IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our results show that adiponectin is generally negatively associated with GH activity, regardless of age. Further, the amount of HMW adiponectin is consistently linked with the level of total adiponectin and not necessarily with previously reported lifespan or insulin sensitivity of these mice. Interestingly, circulating adiponectin levels correlated strongly with inguinal fat mass, implying that the effects of GH on adiponectin are depot specific. Interestingly, rbGH, but not IGF1, decreased circulating total and HMW adiponectin levels. Taken together, these results fill important gaps in the literature related to GH and adiponectin and question the frequently reported associations of total and HMW adiponectin with insulin sensitivity and longevity.

  8. Adiponectin, the past two decades

    PubMed Central

    Wang, Zhao V.; Scherer, Philipp E.

    2016-01-01

    Adiponectin is an adipocyte-specific factor, first described in 1995. Over the past two decades, numerous studies have elucidated the physiological functions of adiponectin in obesity, diabetes, inflammation, atherosclerosis, and cardiovascular disease. Adiponectin, elicited through cognate receptors, suppresses glucose production in the liver and enhances fatty acid oxidation in skeletal muscle, which together contribute to a beneficial metabolic action in whole body energy homeostasis. Beyond its role in metabolism, adiponectin also protects cells from apoptosis and reduces inflammation in various cell types via receptor-dependent mechanisms. Adiponectin, as a fat-derived hormone, therefore fulfills a critical role as an important messenger to communicate between adipose tissue and other organs. A better understanding of adiponectin actions, including the pros and cons, will advance our insights into basic mechanisms of metabolism and inflammation, and potentially pave the way toward novel means of pharmacological intervention to address pathophysiological changes associated with diabetes, atherosclerosis, and cardiometabolic disease. PMID:26993047

  9. Caloric restriction increases adiponectin expression by adipose tissue and prevents the inhibitory effect of insulin on circulating adiponectin in rats.

    PubMed

    Ding, Qi; Ash, Catherine; Mracek, Tomas; Merry, Brian; Bing, Chen

    2012-08-01

    Aging is associated with redistribution of body fat and the development of insulin resistance. White adipose tissue emerges as an important organ in controlling life span. Caloric restriction (CR) delays the rate of aging possibly modulated partly by altering the amount and function of adipose tissue. Adiponectin is a major adipose-derived adipokine that has anti-inflammatory and insulin-sensitizing properties. This study examined the effects of CR on adiposity and gene expression of adiponectin, its receptors (AdipoR1 and AdipoR2) in adipose tissue and in isolated adipocytes of Brown Norway rats that had undergone CR for 4 months or fed ad libitum. The study also determined plasma concentrations of adiponectin and insulin in these animals and whether insulin infusion for 7 days affects adiponectin expression and its circulating concentrations under CR conditions. CR markedly reduced body weight as anticipated, epididymal fat mass and adipocyte size. CR led to an increase in plasma free fatty acid and glycerol (both twofold), and adipose triglyceride lipase messenger RNA (mRNA) in adipose tissue and isolated adipocytes (both >2-fold). Adiponectin mRNA levels were elevated in adipose tissue and adipocytes (both >2-fold) as was plasma adiponectin concentration (2.8-fold) in CR rats. However, CR did not alter tissue or cellular AdipoR1 and AdipoR2 expression. Seven days of insulin infusion decreased adiponectin mRNA in adipose tissue but did not reverse the CR-induced up-regulation of circulating adiponectin levels. Our results suggest that the benefits of CR could be, at least in part, dependent on enhanced expression and secretion of adiponectin by adipocytes.

  10. Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites

    PubMed Central

    Keku, Temitope O.; Vidal, Adriana; Oliver, Shannon; Hoyo, Catherine; Hall, Ingrid J.; Omofoye, Seun; McDoom, Maya; Worley, Kendra; Galanko, Joseph; Sandler, Robert S.; Millikan, Robert

    2014-01-01

    Purpose Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA)n repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study. Methods Participants were African Americans (231cases, 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens, and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5′-exonuclease (Taqman) assay. The IGF-I (CA)n repeat was assayed by PCR, and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. Results The IGF-I (CA)19 repeat was higher in White controls (50%) than African American controls (31%). Whites homozygous for the IGF-I (CA)19 repeat had a nearly two fold increase in risk of colon cancer (OR=1.77; 95%CI=1.15–2.73), but not African Americans (OR= 0.73, 95%CI 0.50–1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR= 0.49, 95%CI 0.28–0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p- trend < 0.05). Conclusions These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans. PMID:22565227

  11. Adiponectin is associated with risk of the metabolic syndrome and insulin resistance in women.

    PubMed

    King, George A; Deemer, Sarah E; Thompson, Dixie L

    2012-12-01

    The purpose of this study was to examine insulin resistance, markers of the metabolic syndrome, cardiovascular disease (CVD) risk, and serum adiponectin concentrations in pre-menopausal Hispanic and non-Hispanic White (NHW) women. This cross-sectional study examined 119 pre-menopausal women (76 Hispanic, 45 NHW) for markers of the metabolic syndrome (ATP III criteria), level of insulin resistance (HOMA-IR), CVD risk factors, and serum total adiponectin concentrations. Relationships between variables were assessed using Student's t-tests, Pearson's and Spearman's Rho correlations, and stepwise multiple regression analysis. Hispanic women had significantly lower adiponectin concentrations than NHW women, even after controlling for body fat (%) (P < 0.01). Number of markers of the metabolic syndrome was inversely related to total adiponectin concentration for all women combined and for NHW women (P ≤ 0.04), but not for Hispanic women. Insulin resistance was inversely related to adiponectin for all women and for NHW women (P < 0.01), but not significantly associated in Hispanic women. Adiponectin concentration was not significantly associated with number of CVD risk factors for these women. While adiponectin was associated with markers of metabolic syndrome and insulin resistance for all women of this study and despite lower adiponectin concentrations for Hispanic women than NHW women, the role of adiponectin to these conditions among Hispanics remains unclear. There was no significant association between adiponectin and CVD risk for these women. Future research should focus on understanding mechanisms for up-regulating adiponectin secretion and if ethnicity affects adiponectin gene expression and secretion given the beneficial effects derived from elevated adiponectin levels.

  12. Fetuin-A downregulates adiponectin through Wnt-PPARγ pathway in lipid induced inflamed adipocyte.

    PubMed

    Agarwal, Soumik; Chattopadhyay, Mrittika; Mukherjee, Sandip; Dasgupta, Suman; Mukhopadhyay, Satinath; Bhattacharya, Samir

    2017-01-01

    Adiponectin secreted from adipocytes is an anti-diabetic and anti-atherogenic adipokine. Adiponectin level is known to fall significantly in obesity induced type 2 diabetes which worsen insulin sensitivity because of aberrant lipid management. However, underlying mechanism of adiponectin decrease in obese diabetic condition is yet unclear. We report here that lowering of plasma adiponectin coincided with the higher Fetuin A (FetA) level in high fat diet (HFD) induced obese diabetic mice. Knock down of FetA gene (FetA(KD)) elevated adiponectin level markedly in HFD mice, while reinforcement of FetA into FetA(KD)HFD mice reduced its level again. These results indicate FetA's involvement in the lowering of adiponectin level in obesity induced diabetic mice. Our findings to understand how FetA could affect adiponectin decrease demonstrated that FetA could enhance Wnt3a expression in the adipocyte of HFD mice. FetA addition to 3T3L1 adipocyte incubation elevated Wnt3a expression in a dose dependent manner. Overexpression of Wnt3a by FetA inhibited PPARγ and adiponectin. FetA failed to reduce PPARγ and adiponectin in Wnt3a gene knocked down 3T3L1` adipocytes. All these suggest that FetA mediate its inhibitory effect on adiponectin through Wnt3a-PPARγ pathway. Inhibition of adiponectin expression through FetA and Wnt3a significantly compromised with the activation of AMPK and its downstream signalling molecules which adversely affected lipid management causing loss of insulin sensitivity. Downregulation of adiponectin in inflamed adipocyte by FetA through the mediation of Wnt3a and PPARγ is a new report.

  13. Expression of adiponectin and adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) in the porcine uterus during the oestrous cycle.

    PubMed

    Smolinska, Nina; Dobrzyn, Kamil; Maleszka, Anna; Kiezun, Marta; Szeszko, Karol; Kaminski, Tadeusz

    2014-04-01

    Adiponectin is a hormone secreted primarily by white adipose tissue. Recent studies have shown that adiponectin and its receptors (AdipoR1 and AdipoR2) are expressed in different reproductive tissues, including the ovary and uterus. This newly discovered endocrine system plays an important role in the regulation of reproductive processes. The expression of the adiponectin system in the porcine uterus during the oestrous cycle has not been researched to date. The aim of the present study was to investigate the presence and changes in adiponectin system expression in the porcine uterus on days 2-3, 10-12, 14-16, and 17-19 of the oestrous cycle. The expression of the adiponectin gene was highest on days 14-16 and 2-3 in the endometrium and myometrium, respectively. In the endometrium, the content of AdipoR1 and AdipoR2 mRNAs was highest on days 10-12, whereas significantly higher expression levels of both genes were noted in the myometrium on days 17-19. The highest content of adiponectin and AdipoR1 protein in the endometrium was reported on days 2-3. In the myometrium, the expression levels of both receptor proteins were significantly higher on days 17-19. Adiponectin system proteins were localized in endometrial epithelial glandular cells, luminal epithelial cells and stromal cells as well as in longitudinal and circular muscles of the myometrium. This study demonstrated the presence of adiponectin, AdipoR1 and AdipoR2 genes and proteins in the porcine uterus and the effect of the stage of the oestrous cycle on the expression of the adiponectin system. Our results suggest that locally synthesized adiponectin directly affects uterine functions.

  14. Docosahexaenoic acid increases cellular adiponectin mRNA and secreted adiponectin protein, as well as PPARγ mRNA, in 3T3-L1 adipocytes.

    PubMed

    Oster, Richard T; Tishinsky, Justine M; Yuan, Zongfei; Robinson, Lindsay E

    2010-12-01

    Adiponectin, a protein secreted from adipose tissue, has been shown to have anti-diabetic and anti-inflammatory effects, but its regulation is not completely understood. Long-chain n-3 fatty acids eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3; DHA) may be involved in adiponectin regulation as they are potential ligands for peroxisome proliferator-activated receptor-γ (PPARγ), a key transcription factor for the adiponectin gene. To examine this, 3T3-L1 adipocytes were incubated with 125 µmol·L-1 EPA, DHA, palmitic, or oleic acids complexed to albumin, or with albumin alone (control) for 24 h. Adipocytes were also incubated for 24 h with EPA and DHA plus bisphenol-A-diglycidyl ether (BADGE), a PPARγ antagonist. Both EPA and DHA increased (p < 0.05) secreted adiponectin concentration compared with the control (44% and 102%, respectively), but did not affect cellular adiponectin protein content. Incubation with BADGE and DHA inhibited increases in secreted adiponectin protein, suggesting that DHA may act through a PPARγ-dependent mechanism. However, BADGE had no effect on EPA-induced increases in secreted adiponectin protein. Only DHA enhanced (p < 0.05) PPARγ and adiponectin mRNA expression compared wtih the control. Our results demonstrate that DHA increases cellular adiponectin mRNA and secreted adiponectin protein in 3T3-L1 adipocytes, possibly by a mechanism involving PPARγ. Moreover, DHA increased adiponectin concentration to a greater extent (40% more, p < 0.05) compared with EPA, emphasizing the need to consider the independent actions of EPA and DHA in adipocytes.

  15. Adiponectin and its receptors: partners contributing to the "vicious circle" leading to the metabolic syndrome?

    PubMed

    Vasseur, Francis

    2006-06-01

    Although already described five years ago, it is only from year 2000, following intensive research in the field of genetics that the adiponectin protein was related with insulin sensitivity, type 2 diabetes and the metabolic syndrome. The story began with a paradox as this protein exclusively secreted by fat tissue was dramatically decreased in patients presenting an excess of fat mass. Later this decrease was reported with insulin resistance and metabolic syndrome associated phenotypes. The search for genetic variants in the adiponectin encoding ACDC gene and epidemio genetic investigations allowed to associate genetic variations of the gene and phenotypic traits of the metabolic syndrome. One of the major points was the correlation of the levels of circulating adiponectin with insulin sensitivity, leading to a better knowledge of the role of adiponectin. Indeed it is now clearly admitted that adiponectin is an insulin sensitizing cytokine. Recently two adiponectin receptors were described and genetic variations in their genes were associated with features of the metabolic syndrome. Interactions of adiponectin with various partners are discussed in view of a better understanding of adiponectin resistance and insulin resistance.

  16. SSA 04-3 LEPTIN/ADIPONECTIN IN CARDIOMETABOLIC DISEASE.

    PubMed

    Lopez-Jaramillo, Patricio

    2016-09-01

    lower in Chinese and South Asians than in Aboriginals and Europeans, and adiponectin was inversely associated with insulin resistance. The authors concluded that ethnic-specific differences in adiponectin may account for the differences in insulin resistance. It was observed that plasma adiponectin concentrations were lower for both Greenlandic Inuit boys and girls, who have a more adverse metabolic profile, than for Danish children. The differences remained after adjustment for body fat percentage, aerobic fitness, age, and puberty. However, in a large study conducted in the United States there were no significant racial or ethnic differences in circulating concentrations of adiponectin, even when adjusted for age, sex, and body composition. This result contrasts with a previous study in adults that reported that circulating concentrations of adiponectin were lower in South Asians even after adjusting for age, sex, and BMI. To explain these contrasting results, it is interesting to consider the proposal that fetal undernutrition produces poor development of structural units such as nephrons, cardiomyocytes, and beta pancreatic cells. These adaptations during fetal programming produce a negative effect in adulthood if food is more abundant in the postnatal period. Nutritional deficiencies during fetal programming through epigenetic mechanisms could affect the expression of genes that result in decreased synthesis of adiponectin. Although it is difficult to establish consistent regional differences, there appear to be considerable differences between developed and developing countries. In Latin America, a Brazilian study reported adiponectin values of 7.11 mg/mL, and we reported concentrations of 5.93 mg/mL in Colombia. In Australian women with metabolic syndrome, however, the values were 13.7 mg/mL, whereas in Indonesian women with metabolic syndrome, the values were much lower (4.9 mg/mL). In US decreased adiponectin concentrations were found in Latino compared

  17. Adiponectin, leptin, and yoga practice.

    PubMed

    Kiecolt-Glaser, Janice K; Christian, Lisa M; Andridge, Rebecca; Hwang, Beom Seuk; Malarkey, William B; Belury, Martha A; Emery, Charles F; Glaser, Ronald

    2012-12-05

    To address the mechanisms underlying hatha yoga's potential stress-reduction benefits, we compared adiponectin and leptin data from well-matched novice and expert yoga practitioners. These adipocytokines have counter-regulatory functions in inflammation; leptin plays a proinflammatory role, while adiponectin has anti-inflammatory properties. Fifty healthy women (mean age=41.32, range=30-65), 25 novices and 25 experts, provided fasting blood samples during three separate visits. Leptin was 36% higher among novices compared to experts, P=.008. Analysis of adiponectin revealed a borderline effect of yoga expertise, P=.08; experts' average adiponectin levels were 28% higher than novices across the three visits. In contrast, experts' average adiponectin to leptin ratio was nearly twice that of novices, P=.009. Frequency of self-reported yoga practice showed significant negative relationships with leptin; more weeks of yoga practice over the last year, more lifetime yoga sessions, and more years of yoga practice were all significantly associated with lower leptin, with similar findings for the adiponectin to leptin ratio. Novices and experts did not show even marginal differences on behavioral and physiological dimensions that might represent potential confounds, including BMI, central adiposity, cardiorespiratory fitness, and diet. Prospective studies addressing increased risk for type II diabetes, hypertension, and cardiovascular disease have highlighted the importance of these adipocytokines in modulating inflammation. Although these health risks are clearly related to more extreme values then we found in our healthy sample, our data raise the possibility that longer-term and/or more intensive yoga practice could have beneficial health consequences by altering leptin and adiponectin production.

  18. Associations of Two Obesity-Related Single-Nucleotide Polymorphisms with Adiponectin in Chinese Children

    PubMed Central

    Gao, Liwang; Zhao, Xiaoyuan; Zhang, Meixian; Wu, Jianxin

    2017-01-01

    Purpose. Genome-wide association studies have found two obesity-related single-nucleotide polymorphisms (SNPs), rs17782313 near the melanocortin-4 receptor (MC4R) gene and rs6265 near the brain-derived neurotrophic factor (BDNF) gene, but the associations of both SNPs with other obesity-related traits are not fully described, especially in children. The aim of the present study is to investigate the associations between the SNPs and adiponectin that has a regulatory role in glucose and lipid metabolism. Methods. We examined the associations of the SNPs with adiponectin in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the study. Results. The SNP rs6265 was significantly associated with adiponectin under an additive model (P = 0.02 and 0.024, resp.) after adjustment for age, gender, and BMI or obesity statuses. The SNP rs17782313 was significantly associated with low adiponectin under a recessive model. No statistical significance was found between the two SNPs and low adiponectin after correction for multiple testing. Conclusion. We demonstrate for the first time that the SNP rs17782313 near MC4R and the SNP rs6265 near BDNF are associated with adiponectin in Chinese children. These novel findings provide important evidence that adiponectin possibly mediates MC4R and BDNF involved in obesity.

  19. Total and high molecular weight adiponectin levels in the rat model of post-myocardial infarction heart failure.

    PubMed

    Kalisz, M; Baranowska, B; Wolinska-Witort, E; Maczewski, M; Mackiewicz, U; Tulacz, D; Gora, M; Martynska, L; Bik, W

    2015-10-01

    Adiponectin is a protein secreted primarily by adipose tissue. It has been suggested that adiponectin plays a protective role in the early phase following myocardial infarction. Our primary aim was to investigate the effects of post-myocardial infarction heart failure well-characterized by left ventricular hemodynamic parameters on the total and high molecular weight adiponectin concentrations in plasma, fat and cardiac tissue. Eight weeks after myocardial infarction or sham operation, total and high molecular weight adiponectin concentrations in plasma, fat, and cardiac tissues were assayed in rats. In addition, hemodynamic parameters and expression of the genes encoding atrial natriuretic peptide and brain natriuretic peptide in left ventricle were evaluated. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels in left ventricle tissue were higher in rats with myocardial infarction-induced heart failure compared with the controls. Similarly, total adiponectin concentration was increased in left ventricle (but not in right ventricle) in rats with post-myocardial infarction heart failure. In contrast, adiponectin levels in plasma and cardiac adipose tissue in rats with post-myocardial infarction heart failure were lower than in sham-operated animals. Furthermore, there were no significant differences in levels of high molecular weight adiponectin in plasma, cardiac tissue or adipose tissue between these two groups. We conclude that in the rat model of post-myocardial infarction heart failure, adiponectin level is increased in left ventricle tissue. This is accompanied by decreased adiponectin levels in plasma and cardiac adipose tissue.

  20. Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease

    PubMed Central

    Persson, Jonas; Strawbridge, Rona J; McLeod, Olga; Gertow, Karl; Silveira, Angela; Baldassarre, Damiano; Van Zuydam, Natalie; Shah, Sonia; Fava, Cristiano; Gustafsson, Stefan; Veglia, Fabrizio; Sennblad, Bengt; Larsson, Malin; Sabater-Lleal, Maria; Leander, Karin; Gigante, Bruna; Tabak, Adam; Kivimaki, Mika; Kauhanen, Jussi; Rauramaa, Rainer; Smit, Andries J; Mannarino, Elmo; Giral, Philippe; Humphries, Steve E; Tremoli, Elena; de Faire, Ulf; Lind, Lars; Ingelsson, Erik; Hedblad, Bo; Melander, Olle; Kumari, Meena; Hingorani, Aroon; Morris, Andrew D; Palmer, Colin N A; Lundman, Pia; Öhrvik, John; Söderberg, Stefan; Hamsten, Anders

    2015-01-01

    Background Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT. Methods and Results Baseline plasma adiponectin concentration was tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n =1777; men, n =1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (β =−0.018, P<0.001) in men but not in women (β =−0.006, P =0.185; P for interaction =0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (β =−0.0022, P =0.047), whereas no association was seen in women (0.0007, P =0.475; P for interaction =0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82, 95% CI 0.54 to 1.25). A gene score of adiponectin-raising alleles in 6 loci, reported recently in a large multi-ethnic meta-analysis, was inversely associated with baseline mean bifurcation IMT in men (β =−0.0008, P =0.004) but not in women (β =−0.0003, P =0.522; P for interaction =0.007). Conclusions This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted. PMID:26276317

  1. The aporphine alkaloid boldine induces adiponectin expression and regulation in 3T3-L1 cells.

    PubMed

    Yu, Bangning; Cook, Carla; Santanam, Nalini

    2009-10-01

    Adiponectin is an adipokine secreted by differentiated adipocytes. Clinical studies suggest a negative correlation between oxidative stress and adiponectin levels in patients with metabolic syndrome or cardiovascular disease. Natural compounds that can prevent oxidative stress mediated inhibition of adiponectin may be potentially therapeutic. Boldine, an aporphine alkaloid abundant in the medicinal plant Peumus boldus, is a powerful antioxidant. The current study demonstrates the effects of boldine on the expression of adiponectin and its regulators, CCAAT/enhancer binding protein-alpha (C/EBPalpha) and peroxisome proliferator-activated receptor (PPAR)-gamma, in 3T3-L1 cells. Differentiated 3T3-L1 adipocytes were exposed to either hydrogen peroxide (H(2)O(2)) (100 microM) or tumor necrosis factor-alpha (TNFalpha) (1 ng/mL) for 24 hours in the presence or absence of increasing concentrations of boldine (5-100 microM). Quantitative polymerase chain reaction showed that both the oxidants decreased the mRNA levels of adiponectin, PPARgamma, and C/EBPalpha to half of the control levels. Boldine, at all concentrations, counteracted the inhibitory effect of H(2)O(2) or TNFalpha and increased the expression of adiponectin and its regulators. The effect of boldine on adiponectin expression was biphasic, with the lower concentrations (5-25 microM) having a larger inductive effect compared to higher concentrations (50-100 microM). Boldine treatment alone in the absence of H(2)O(2) or TNFalpha was also able to induce adiponectin at the inductive phase of adipogenesis. Peroxisome proliferator response element-luciferase promoter transactivity analysis showed that boldine interacts with the PPAR response element and could potentially modulate PPAR responsive genes. Our results indicate that boldine is able to modulate the expression of adiponectin and its regulators in 3T3-L1 cells and has the potential to be beneficial in obesity-related cardiovascular disease.

  2. The Aporphine Alkaloid Boldine Induces Adiponectin Expression and Regulation in 3T3-L1 Cells

    PubMed Central

    Yu, Bangning; Cook, Carla

    2009-01-01

    Abstract Adiponectin is an adipokine secreted by differentiated adipocytes. Clinical studies suggest a negative correlation between oxidative stress and adiponectin levels in patients with metabolic syndrome or cardiovascular disease. Natural compounds that can prevent oxidative stress mediated inhibition of adiponectin may be potentially therapeutic. Boldine, an aporphine alkaloid abundant in the medicinal plant Peumus boldus, is a powerful antioxidant. The current study demonstrates the effects of boldine on the expression of adiponectin and its regulators, CCAAT/enhancer binding protein-α (C/EBPα) and peroxisome proliferator-activated receptor (PPAR)-γ, in 3T3-L1 cells. Differentiated 3T3-L1 adipocytes were exposed to either hydrogen peroxide (H2O2) (100 μM) or tumor necrosis factor-α (TNFα) (1 ng/mL) for 24 hours in the presence or absence of increasing concentrations of boldine (5–100 μM). Quantitative polymerase chain reaction showed that both the oxidants decreased the mRNA levels of adiponectin, PPARγ, and C/EBPα to half of the control levels. Boldine, at all concentrations, counteracted the inhibitory effect of H2O2 or TNFα and increased the expression of adiponectin and its regulators. The effect of boldine on adiponectin expression was biphasic, with the lower concentrations (5–25 μM) having a larger inductive effect compared to higher concentrations (50–100 μM). Boldine treatment alone in the absence of H2O2 or TNFα was also able to induce adiponectin at the inductive phase of adipogenesis. Peroxisome proliferator response element-luciferase promoter transactivity analysis showed that boldine interacts with the PPAR response element and could potentially modulate PPAR responsive genes. Our results indicate that boldine is able to modulate the expression of adiponectin and its regulators in 3T3-L1 cells and has the potential to be beneficial in obesity-related cardiovascular disease. PMID:19857072

  3. Adiponectin as an anti-inflammatory factor

    PubMed Central

    Ouchi, Noriyuki; Walsh, Kenneth

    2009-01-01

    Obesity is characterized by low-grade systemic inflammation. Adiponectin is an adipose tissue-derived hormone, which is downregulated in obesity. Adiponectin displays protective actions on the development of various obesity-linked diseases. Several clinical studies demonstrate the inverse relationship between plasma adiponectin levels and several inflammatory markers including C-reactive protein. Adiponectin attenuates inflammatory responses to multiple stimuli by modulating signaling pathways in a variety of cell types. The anti-inflammatory properties of adiponectin may be a major component of its beneficial effects on cardiovascular and metabolic disorders including atherosclerosis and insulin resistance. In this reviews, we focus on the role of adiponectin in regulation of inflammatory response and discuss its potential as an antiinflammatory marker. PMID:17343838

  4. Globular adiponectin induces a pro-inflammatory response in human astrocytic cells

    SciTech Connect

    Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana; Klegeris, Andis; Little, Jonathan P.

    2014-03-28

    Highlights: • Adiponectin receptors are expressed in human astrocytes. • Globular adiponectin induces secretion of IL-6 and MCP-1 from cultured astrocytes. • Adiponectin may play a pro-inflammatory role in astrocytes. - Abstract: Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observed link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3 K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes.

  5. Adiponectin as a routine clinical biomarker.

    PubMed

    Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro

    2014-01-01

    Adiponectin is a protein synthesized and secreted predominantly by adipocytes into the peripheral blood. However, circulating adiponectin level is inversely related with body weight, especially visceral fat accumulation. The mechanism of this paradoxical relation remains obscure. Low circulating adiponectin concentrations (hypoadiponectinemia; <4 μg/mL) are associated with a variety of diseases, including dysmetabolism (type 2 diabetes, insulin resistance, hypertension, dyslipidemia, metabolic syndrome, hyperuricemia), atherosclerosis (coronary artery disease, stroke, peripheral artery disease), sleep apnea, non-alcoholic fatty liver disease, gastritis and gastro-esophageal reflux disease, inflammatory bowel diseases, pancreatitis, osteoporosis, and cancer (endometrial cancer, postmenopausal breast cancer, leukemia, colon cancer, gastric cancer, prostate cancer). On the other hand, hyperadiponectinemia is associated with cardiac, renal and pulmonary diseases. This review article focuses on the significance of adiponectin as a clinical biomarker of obesity-related diseases. Routine measurement of adiponectin in patients with lifestyle-related diseases is highly recommended.

  6. Expression of adiponectin and its receptors in the porcine hypothalamus during the oestrous cycle.

    PubMed

    Kaminski, T; Smolinska, N; Maleszka, A; Kiezun, M; Dobrzyn, K; Czerwinska, J; Szeszko, K; Nitkiewicz, A

    2014-06-01

    Adiponectin is a hormonal link between obesity and reproduction, and its actions are mediated by two types of receptors: adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). This study compares the expression levels of adiponectin and adiponectin receptor mRNAs and proteins in selected areas of the porcine hypothalamus responsible for GnRH production and secretion: the mediobasal hypothalamus (MBH), pre-optic area (POA) and stalk median eminence (SME). The tissue samples were harvested on days 2-3, 10-12, 14-16 and 17-19 of the oestrous cycle. Adiponectin mRNA expression in MBH was significantly lower on days 14-16, whereas in SME, the most pronounced gene expression was found on days 2-3 of the cycle (p < 0.05). Adiponectin protein in MBH was most abundant on days 17-19 and in POA on days 2-3 (p < 0.05). Adiponectin protein expression in SME was at similar level throughout the most of the cycle with a statistically significant drop (p < 0.05) on days 14-16. AdipoR1 gene expression in POA was potentiated on days 2-3 and 10-12 of the oestrous cycle (p < 0.05). In SME, the highest AdipoR1 mRNA expression was noted on days 2-3 (p < 0.05). The concentrations of the AdipoR1 protein in POA were similar throughout the luteal phase (days 2-14 of the cycle), and they decreased on days 17-19 (p < 0.05). In SME, AdipoR1 protein expression peak occurred on days 2-3 (p < 0.05). The expression patterns of the AdipoR2 gene in MBH, POA and SME revealed the highest mRNA levels on days 2-3 of the cycle (p < 0.05). The highest content of AdipoR2 protein in MBH was reported on days 2-3 (p < 0.05), while in POA on days 17-19 and in SME on days 10-12 and 14-16 (p < 0.05). This study demonstrated that adiponectin and adiponectin receptor mRNAs and proteins are present in the porcine hypothalamus and that their expression levels are determined by the pig's endocrine status related to the oestrous cycle.

  7. Circulating Adiponectin and Risk of Endometrial Cancer

    PubMed Central

    Zheng, Qiaoli; Wu, Haijian; Cao, Jiang

    2015-01-01

    Background Adiponectin is an insulin-sensitizing hormone produced by adipocytes. It has been suggested to be involved in endometrial tumorigenesis. Published data have shown inconsistent results for the association between circulating adiponectin levels and endometrial cancer. In this study, we conducted a meta-analysis to evaluate the predictive value of circulating adiponectin levels on the development of endometrial cancer. Methods PubMed, Embase, ISI web of knowledge, and Cochrane databases were searched for all eligible studies, and the summary relative risk (SRR) was calculated. Additionally, we performed dose-response analysis with eight eligible studies. Results A total of 1,955 cases and 3,458 controls from 12 studies were included. The SRR for the ‘highest’ vs ‘lowest’ adiponectin levels indicated high adiponectin level reduced the risk of endometrial cancer [SRR = 0.40, 95% confidence interval (CI), 0.33–0.66]. Results from the subgroup analyses were consistent with the overall analysis. The SRR for each 1 µg/ml increase of adiponectin indicated a 3% reduction in endometrial cancer risk (95% CI: 2%–4%), and a 14% reduction for each increase of 5 µg/ml (95% CI: 9%–19%). No evidence of publication bias was found. Conclusions This meta-analysis demonstrates that low level of circulating adiponectin is a risk factor for endometrial cancer. PMID:26030130

  8. Triiodothyronine modulates the expression of leptin and adiponectin in 3T3-L1 adipocytes

    PubMed Central

    de Oliveira, Miriane; Síbio, Maria Teresa De; Olimpio, Regiane Marques Castro; Moretto, Fernanda Cristina Fontes; Luvizotto, Renata de Azevedo Melo; Nogueira, Celia Regina

    2015-01-01

    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. PMID:25993072

  9. Adiposity distribution influences circulating adiponectin levels.

    PubMed

    Guenther, Mitchell; James, Roland; Marks, Jacqueline; Zhao, Shi; Szabo, Aniko; Kidambi, Srividya

    2014-10-01

    Thirty percent of obese individuals are metabolically healthy and were noted to have increased peripheral obesity. Adipose tissue is the primary source of adiponectin, an adipokine with insulin-sensitizing and anti-inflammatory properties. Lower adiponectin levels are observed in individuals with obesity and those at risk for cardiovascular disease. Conversely, higher levels are noted in some obese individuals who are metabolically healthy. Our objective was to determine whether abdominal adiposity distribution, rather than body mass index (BMI) status, influences plasma adiponectin level. A total of 424 subjects (female, 255) of Northern European ancestry were recruited from "Take Off Pounds Sensibly" weight loss club members. Demographics, anthropometrics, and dual-emission x-ray absorptiometry of the whole body, and computed tomography scan of the abdomen were performed to obtain total body fat content and to quantify subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), respectively. Laboratory measurements included fasting plasma glucose, insulin, lipid panel, and adiponectin. Age- and gender-adjusted correlation analyses showed that adiponectin levels were negatively correlated with BMI, waist circumference, triglycerides, total fat mass, and VAT. A positive correlation was noted with high-density lipoprotein cholesterol and fat-free mass (P < 0.05). SAT-to-VAT ratios were also significantly associated with adiponectin (r = 0.13, P = 0.001). Further, the best positive predictors for plasma adiponectin were found to be SAT-to-VAT ratios and gender by regression analyses (P < 0.01). Abdominal adiposity distribution is an important predictor of plasma adiponectin and obese individuals with higher SAT-to-VAT ratios may have higher adiponectin levels.

  10. Association between Risk Factors for Vascular Dementia and Adiponectin

    PubMed Central

    Lee, Won Taek; Park, Kyung Ah

    2014-01-01

    Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain. Case-control studies demonstrate the association between low adiponectin and increased risk of stroke, hypertension, and diabetes. This review summarizes the recent findings on the association between risk factors for vascular dementia and adiponectin. To emphasize this relationship, we will discuss the importance of research regarding the role of adiponectin in vascular dementia. PMID:24860814

  11. Adiponectin Signaling Regulates Lipid Production in Human Sebocytes

    PubMed Central

    Jung, Yu Ra; Lee, Jin-Hyup; Sohn, Kyung-Cheol; Lee, Young; Seo, Young-Joon; Kim, Chang-Deok; Lee, Jeung-Hoon; Hong, Seung-Phil; Seo, Seong-Jun; Kim, Seong-Jin; Im, Myung

    2017-01-01

    Adiponectin plays important roles in metabolic function, inflammation and multiple biological activities in various tissues. However, evidence for adiponectin signaling in sebaceous glands is lacking, and its role remains to be clarified. This study investigated the role of adiponectin in lipid production in sebaceous glands in an experimental study of human sebocytes. We demonstrated that human sebaceous glands in vivo and sebocytes in vitro express adiponectin receptor and that adiponectin increased cell proliferation. Moreover, based on a lipogenesis study using Oil Red O, Nile red staining and thin layer chromatography, adiponectin strongly upregulated lipid production in sebocytes. In three-dimensional culture of sebocytes, lipid synthesis was markedly enhanced in sebocytes treated with adiponectin. This study suggested that adiponectin plays a significant role in human sebaceous gland biology. Adiponectin signaling is a promising target in the clinical management of barrier disorders in which sebum production is decreased, such as in atopic dermatitis and aged skin. PMID:28081218

  12. The Kampo medicines Orengedokuto, Bofutsushosan and Boiogito have different activities to regulate gene expressions in differentiated rat white adipocytes: comprehensive analysis of genetic profiles.

    PubMed

    Yamakawa, Jun-ichi; Ishigaki, Yasuhito; Takano, Fumihide; Takahashi, Takashi; Yoshida, Junko; Moriya, Junji; Takata, Takanobu; Tatsuno, Takanori; Sasaki, Kenroh; Ohta, Tomihisa; Takegami, Tsutomu; Yoshizaki, Fumihiko

    2008-11-01

    Three Kampo medicines, Boiogito (BOT), Bofutsushosan (BTS) and Orengedokuto (OGT), used for obese patients were investigated for their effects on adipogenesis in cultured rat white adipocytes. Administration of the three extracts suppressed adipogenesis in concentration-dependent manners (1-100 microg/ml) without any cytotoxicity. Changes in mRNA expression levels were analyzed using a Rat 230 2.0 Affymetrix GeneChip microarray system. DNA microarray analysis (total probe set: 31099) using cDNAs prepared from adipocytes revealed that BOT, BTS and OGT increased the expression of 133-150 genes and decreased the expression of 42-110 genes by > or =2-fold. We identified 329 downregulated genes and 189 upregulated genes among a total set of 514 probes (overlap: 4). Overall, genes related to cellular movement, cell death, cell growth/differentiation and immune responses were the most downregulated, while those related to lipid metabolism and cell signaling were the most upregulated. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assays were conducted to confirm the microarray results. Analysis of the clustering profiles of the microarray results revealed that BOT and BTS changed the expression levels of similar genes mainly involved in small molecule biochemistry and cell differentiation, while OGT altered 10 genes related to lipid metabolism, in contrast to the effects of BOT and BTS. We also measured mRNA expression levels of seven selected genes highly contributing to the lipid metabolism by using semiquantitative RT-PCR assay, that were acetyl-Coenzyme A carboxylase alpha (ACACA), AE binding protein 1 (AEBP1), patatin-like phospholipase domain containing 8 (PNPLA8), secretoglobin (SCGB1A1), adrenergic (ADRB3), adiponectin (ADIPOQ), monoglyceride lipase (MGLL). Beta-actin (ACTB) gene was used as an endogenous internal standard. The present findings indicate that these three herbal extracts have the potential to prevent adipogenesis in rat

  13. LOW CIRCULATING MATERNAL ADIPONECTIN IN PATIENTS WITH PYELONEPHRITIS: ADIPONECTIN AT THE CROSSROADS OF PREGNANCY AND INFECTION

    PubMed Central

    Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Erez, Offer; Mittal, Pooja; Kim, Sun Kwon; Gotsch, Francesca; Lamont, Ronald; Ogge, Giovanna; Pacora, Percy; Goncalves, Luis; Kim, Chong Jai; Gomez, Ricardo; Espinoza, Jimmy; Hassan, Sonia S.; Kusanovic, Juan Pedro

    2009-01-01

    Objective An emerging theme in modern biology is that adipose tissue can respond to metabolic stress, and to inflammatory stimuli, by regulating the secretion of a complex network of soluble mediators, termed adipokines. Adiponectin, the most prevalent circulating adipokine in human, has profound insulin-sensitizing and anti-inflammatory properties. Indeed, the notion that adiponectin plays an important role in the interactions between the metabolic and the immune systems has been strongly suggested. Thus, the aim of this study was to determine if pyelonephritis during pregnancy is associated with changes in maternal serum adiponectin concentrations. Study design This cross-sectional study included women in the following groups: 1) normal pregnant women (n=200); and 2) pregnant women with pyelonephritis (n=50). Maternal plasma adiponectin concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results 1) The median maternal plasma adiponectin concentration was lower in patients with pyelonephritis than in those with a normal pregnancy (p<0.001); 2) among pregnant women with a normal weight, patients with pyelonephritis had a lower median plasma adiponectin concentration than those with a normal pregnancy (p<0.001); 3) similarly, among overweight/obese patients, those with pyelonephritis had a lower median plasma adiponectin concentration than those with a normal pregnancy (p<0.001); and 4) the presence of pyelonephritis was independently associated with maternal plasma adiponectin concentrations after adjustment for maternal age, smoking, gestational age at sampling, and pre-gestational BMI. Conclusion 1) The findings that acute pyelonephritis in pregnancy is characterized by low maternal plasma concentrations of adiponectin in both lean and overweight/obese patients are novel and concur with the anti-inflammatory properties of adiponectin; and 2) the results of this study support the notion that adiponectin may play a role in the

  14. Dietary Japanese millet protein ameliorates plasma levels of adiponectin, glucose, and lipids in type 2 diabetic mice.

    PubMed

    Nishizawa, Naoyuki; Togawa, Tubasa; Park, Kyung-Ok; Sato, Daiki; Miyakoshi, Yo; Inagaki, Kazuya; Ohmori, Norimasa; Ito, Yoshiaki; Nagasawa, Takashi

    2009-02-01

    Millet is an important food crop in Asia and Africa, but the health benefits of dietary millet are little known. This study defined the effects of dietary Japanese millet on diabetic mice. Feeding of a high-fat diet containing Japanese millet protein concentrate (JMP, 20% protein) to type 2 diabetic mice for 3 weeks significantly increased plasma levels of adiponectin and high-density lipoprotein cholesterol (HDL cholesterol) and decreased the levels of glucose and triglyceride as compared to control. The starch fraction of Japanese millet had no effect on glucose or adiponectin levels, but the prolamin fraction beneficially modulated plasma glucose and insulin concentrations as well as adiponectin and tumor necrosis factor-alpha gene expression. Considering the physiological significance of adiponectin and HDL cholesterol levels in type 2 diabetes, insulin resistance, and cardiovascular disease, our findings imply that dietary JMP has the potential to ameliorate these diseases.

  15. Adiponectin plays an important role in efficient energy usage under energy shortage.

    PubMed

    Saito, Kiyomi; Arata, Satoru; Hosono, Tomohiko; Sano, Yoshihiro; Takahashi, Katsuhiko; Choi-Miura, Nam-Ho; Nakano, Yasuko; Tobe, Takashi; Tomita, Motowo

    2006-07-01

    Adiponectin is an adipose tissue-specific secretory protein known to be an insulin-sensitizing protein. In this study, we generated adiponectin sense and antisense transgenic (Tg) mice to investigate whether adiponectin plays a role in the regulation of energy homeostasis during the growth stage. Spontaneous motor activity of antisense Tg mice were markedly reduced during fasting, particularly in young female mice, compared with wild type (Wt) and sense Tg mice. Furthermore, both body weight and adipose tissue mass of the antisense female Tg mice drastically reduced during fasting. To examine the relationship between the collapse of abdominal white adipose tissue (WAT) and serum adiponectin level, we measured the expression of genes related to energy expenditure, such as uncoupling protein (UCP). Notably, the mRNA of UCP1 in the WAT of antisense Tg female mice was markedly less than that of Wt mice and the UCP1 mRNA was strongly increased during fasting. These findings suggest that the serum adiponectin is important to maintaining energy homeostasis under energy shortage conditions, such as over female pubertal development.

  16. Retinol-binding protein 7 is an endothelium-specific PPARγ cofactor mediating an antioxidant response through adiponectin

    PubMed Central

    Hu, Chunyan; Keen, Henry L.; Lu, Ko-Ting; Liu, Xuebo; Davis, Deborah R.; Ibeawuchi, Stella-Rita C.; Vogel, Silke; Quelle, Frederick W.; Sigmund, Curt D.

    2017-01-01

    Impaired PPARγ activity in endothelial cells causes oxidative stress and endothelial dysfunction which causes a predisposition to hypertension, but the identity of key PPARγ target genes that protect the endothelium remain unclear. Retinol-binding protein 7 (RBP7) is a PPARγ target gene that is essentially endothelium specific. Whereas RBP7-deficient mice exhibit normal endothelial function at baseline, they exhibit severe endothelial dysfunction in response to cardiovascular stressors, including high-fat diet and subpressor angiotensin II. Endothelial dysfunction was not due to differences in weight gain, impaired glucose homeostasis, or hepatosteatosis, but occurred through an oxidative stress–dependent mechanism which can be rescued by scavengers of superoxide. RNA sequencing revealed that RBP7 was required to mediate induction of a subset of PPARγ target genes by rosiglitazone in the endothelium including adiponectin. Adiponectin was selectively induced in the endothelium of control mice by high-fat diet and rosiglitazone, whereas RBP7 deficiency abolished this induction. Adiponectin inhibition caused endothelial dysfunction in control vessels, whereas adiponectin treatment of RBP7-deficient vessels improved endothelium-dependent relaxation and reduced oxidative stress. We conclude that RBP7 is required to mediate the protective effects of PPARγ in the endothelium through adiponectin, and RBP7 is an endothelium-specific PPARγ target and regulator of PPARγ activity. PMID:28352663

  17. Polymorphism of adiponectin (45T/G) and adiponectin receptor-2 (795G/A) in an Iranian population: relation with insulin resistance and response to treatment with pioglitazone in patients with type 2 diabetes mellitus.

    PubMed

    Namvaran, Fatemeh; Rahimi-Moghaddam, Parvaneh; Azarpira, Negar; Dabbaghmanesh, Mohammad Hosein

    2012-05-01

    Adiponectin, an adipose-derived plasma protein, is reduced in patients with obesity and type 2 diabetes. Thiazolidinediones can increase adiponectin levels and improve insulin sensitivity. This study investigated the associations between type 2 diabetes and two single-nucleotide polymorphisms in the adiponectin (45T/G) and adiponectin receptor-2 gene (795G/A), and investigated whether these genetic variants affect the response to pioglitazone in Iranian patients with type 2 diabetes. We genotyped 128 non-diabetic participants and 101 patients with type 2 diabetes for 45T/G and 795G/A with polymerase chain reaction-restriction fragment length polymorphism assays. Patients were treated with pioglitazone for 12 weeks, after which we compared laboratory parameters in these two groups. Fasting blood sugar differed significantly in individuals with different 795G/A genotypes after pioglitazone treatment (P = 0.009). The mean decrease in insulin/glucose ratio after treatment also differed significantly in individuals with different 45T/G genotypes (P = 0.035). The T allele frequency for 45T/G was 87.11% in controls versus 81.68% in patients (P = 0.071). The TG and GG genotypes were more frequent in patients (P = 0.032). The G allele frequency for 795G/A was 76.17% in controls versus 80.20% in patients (P = 0.179). 795G/A variants were not significantly different between patient and control group. The adiponectin gene 45T/G mutation may be an important determinant of type 2 diabetes in the Iranian population. However, adiponectin 45T/G and adiponectin receptor-2 795G/A polymorphisms were not significantly associated with the response to pioglitazone in our sample.

  18. Hypoxia-inducible Factor 1α Regulates a SOCS3-STAT3-Adiponectin Signal Transduction Pathway in Adipocytes*

    PubMed Central

    Jiang, Changtao; Kim, Jung-Hwan; Li, Fei; Qu, Aijuan; Gavrilova, Oksana; Shah, Yatrik M.; Gonzalez, Frank J.

    2013-01-01

    Obesity has been identified as a major risk factor for type 2 diabetes, characterized by insulin resistance in insulin target tissues. Hypoxia-inducible factor 1α (HIF1α) regulates pathways in energy metabolism that become dysregulated in obesity. Earlier studies revealed that HIF1α in adipose tissue is markedly elevated in high-fat diet-fed mice that are obese and insulin-resistant. Genetic ablation of HIF1α in adipose tissue decreased insulin resistance and obesity, accompanied by increased serum adiponectin levels. However, the exact mechanism whereby HIF1α regulates adiponectin remains unclear. Here, acriflavine (ACF), an inhibitor of HIF1α, induced the expression of adiponectin and reduced the expression of SOCS3 in cultured 3T3-L1 adipocytes. Mechanistic studies revealed that HIF1α suppressed the expression of adiponectin through a SOCS3-STAT3 pathway. Socs3 was identified as a novel HIF1α target gene based on chromatin immunoprecipitation and luciferase assays. STAT3 directly regulated adiponectin in vitro in cultured 3T3-L1 adipocytes. ACF was found to prevent diet-induced obesity and insulin resistance. In vivo, ACF also regulated the SOCS3-STAT3-adiponectin pathway, and inhibition of HIF1α in adipose tissue was essential for ACF to improve the SOCS3-STAT3-adiponectin pathway to counteract insulin resistance. This study provides evidence for a novel target gene and signal transduction pathway in adipocytes and indicates that inhibitors of HIF1α have potential utility for the treatment of obesity and type 2 diabetes. PMID:23255598

  19. Low-molecular-weight adiponectin is more closely associated with disease activity of rheumatoid arthritis than other adiponectin multimeric forms.

    PubMed

    Li, Ping; Yang, Li; Ma, Cui-Li; Liu, Bo; Zhang, Xin; Ding, Rui; Bi, Li-qi

    2015-06-01

    Adiponectin is divided into high-molecular-weight (HMW), medium-molecular-weight (MMW), and low-molecular-weight (LMW) forms. These forms differ not only in the number of adiponectin molecules but also in their biological activity. There are conflicting findings regarding the role of adiponectin in rheumatoid arthritis (RA). Moreover, few reports have described the relationships between serum adiponectin multimers levels and RA. Therefore, we examined the association of total adiponectin and its multimers with RA. Two study groups were examined: 180 recently diagnosed untreated RA patients with disease duration less than 1 year (RA group) and 160 age- and sex-matched control subjects (control group). RA-related factors, blood pressure, body mass index, glucose, complete lipid profile, and adiponectin multimers were measured. The levels of total adiponectin and each multimer of adiponectin were significantly lower in the RA than in the control (P < 0.01). Serum levels of total, HMW, MMW, and LMW were positively correlated with triglycerides levels and negatively correlated with the Disease Activity Score for 28 joints (DAS28). Multivariate regression analysis showed that total, HMW, and MMW adiponectin were independently associated with serum triglycerides level. LMW adiponectin was independently correlated with serum triglycerides level and DAS28. The decreased LMW adiponectin levels may be associated with disease activity of RA.

  20. Adiponectin and Insulin in Gray Seals during Suckling and Fasting: Relationship with Nutritional State and Body Mass during Nursing in Mothers and Pups.

    PubMed

    Bennett, K A; Hughes, J; Stamatas, S; Brand, S; Foster, N L; Moss, S E W; Pomeroy, P P

    2015-01-01

    Animals that fast during breeding and/or development, such as phocids, must regulate energy balance carefully to maximize reproductive fitness and survival probability. Adiponectin, produced by adipose tissue, contributes to metabolic regulation by modulating sensitivity to insulin, increasing fatty acid oxidation by liver and muscle, and promoting adipogenesis and lipid storage in fat tissue. We tested the hypotheses that (1) circulating adiponectin, insulin, or relative adiponectin gene expression is related to nutritional state, body mass, and mass gain in wild gray seal pups; (2) plasma adiponectin or insulin is related to maternal lactation duration, body mass, percentage milk fat, or free fatty acid (FFA) concentration; and (3) plasma adiponectin and insulin are correlated with circulating FFA in females and pups. In pups, plasma adiponectin decreased during suckling (linear mixed-effects model [LME]: T = 4.49; P < 0.001) and the early postweaning fast (LME: T = 3.39; P = 0.004). In contrast, their blubber adiponectin gene expression was higher during the early postweaning fast than early in suckling (LME: T = 2.11; P = 0.046). Insulin levels were significantly higher in early (LME: T = 3.52; P = 0.004) and late (LME: T = 6.99; P < 0.001) suckling than in fasting and, given the effect of nutritional state, were also positively related to body mass (LME: T = 3.58; P = 0.004). Adiponectin and insulin levels did not change during lactation and were unrelated to milk FFA or percentage milk fat in adult females. Our data suggest that adiponectin, in conjunction with insulin, may facilitate fat storage in seals and is likely to be particularly important in the development of blubber reserves in pups.

  1. Adiponectin: a biomarker of obesity-induced insulin resistance in adipose tissue and beyond.

    PubMed

    Lu, Jin-Ying; Huang, Kuo-Chin; Chang, Lin-Chau; Huang, Ying-Shing; Chi, Yu-Chiao; Su, Ta-Chan; Chen, Chi-Ling; Yang, Wei-Shiung

    2008-09-01

    Adiponectin is one of the most thoroughly studied adipocytokines. Low plasma levels of adiponectin are found to associate with obesity, metabolic syndrome, diabetes and many other human diseases. From animal experiments and human studies, adiponectin has been shown to be a key regulator of insulin sensitivity. In this article, we review the evidence and propose that hypo-adiponectinemia is not a major cause of obesity. Instead, it is the result of obesity-induced insulin resistance in the adipose tissue. Hypo-adiponectinemia then mediates the metabolic effects of obesity on the other peripheral tissues, such as liver and skeletal muscle and may also exert some direct effects on end-organ damage. We propose that deciphering the molecular details governing the adiponectin gene expression and protein secretion will lead us to more comprehensive understanding of the mechanisms of insulin resistance in the adipose tissue and provide us new avenues for the therapeutic intervention of obesity and insulin resistance-related human disorders.

  2. Leptin and adiponectin in the female life course.

    PubMed

    Lecke, S B; Morsch, D M; Spritzer, P M

    2011-05-01

    Adipose tissue secretes a variety of adipokines, including leptin and adiponectin, which are involved in endocrine processes regulating glucose and fatty metabolism, energy expenditure, inflammatory response, immunity, cardiovascular function, and reproduction. The present article describes the fluctuations in circulating leptin and adiponectin as well as their patterns of secretion in women from birth to menopause. During pregnancy, leptin and adiponectin seem to act in an autocrine/paracrine fashion in the placenta and adipose tissue, playing a role in the maternal-fetal interface and contributing to glucose metabolism and fetal development. In newborns, adiponectin levels are two to three times higher than in adults. Full-term newborns have significantly higher leptin and adiponectin levels than preterms, whereas small-for-gestational-age infants have lower levels of these adipokines than adequate-for-gestational-age newborns. However, with weight gain, leptin concentrations increase significantly. Children between 5 and 8 years of age experience an increase in leptin and a decrease in adiponectin regardless of body mass index, with a reversal of the newborn pattern for adiponectin: plasma adiponectin levels at age five are inversely correlated with percentage of body fat. In puberty, leptin plays a role in the regulation of menstrual cycles. In adults, it has been suggested that obese individuals exhibit both leptin resistance and decreased serum adiponectin levels. In conclusion, a progressive increase in adiposity throughout life seems to influence the relationship between leptin and adiponectin in women.

  3. Increasing adipocyte lipoprotein lipase improves glucose metabolism in high fat diet-induced obesity.

    PubMed

    Walton, R Grace; Zhu, Beibei; Unal, Resat; Spencer, Michael; Sunkara, Manjula; Morris, Andrew J; Charnigo, Richard; Katz, Wendy S; Daugherty, Alan; Howatt, Deborah A; Kern, Philip A; Finlin, Brian S

    2015-05-01

    Lipid accumulation in liver and skeletal muscle contributes to co-morbidities associated with diabetes and obesity. We made a transgenic mouse in which the adiponectin (Adipoq) promoter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissue lipid storage. These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well as increased energy expenditure when challenged with a high fat diet (HFD). To identify the mechanism(s) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to reduce peripheral lipotoxicity, but we found no evidence for this. Instead, characterization of the adipose tissue of the male mice after HFD challenge revealed that the mRNA levels of peroxisome proliferator-activated receptor-γ (PPARγ) and a number of PPARγ-regulated genes were higher in the epididymal fat pads of Adipoq-LPL mice than control mice. This included adiponectin, whose mRNA levels were increased, leading to increased adiponectin serum levels in the Adipoq-LPL mice. In many respects, the adipose phenotype of these animals resembles thiazolidinedione treatment except for one important difference, the Adipoq-LPL mice did not gain more fat mass on HFD than control mice and did not have increased expression of genes in adipose such as glycerol kinase, which are induced by high affinity PPAR agonists. Rather, there was selective induction of PPARγ-regulated genes such as adiponectin in the adipose of the Adipoq-LPL mice, suggesting that increasing adipose tissue LPL improves glucose metabolism in diet-induced obesity by improving the adipose tissue phenotype. Adipoq-LPL mice also have increased energy expenditure.

  4. Polymorphisms FTO rs9939609, PPARG rs1801282 and ADIPOQ rs4632532 and rs182052 but not lifestyle are associated with obesity related-traits in Mexican children.

    PubMed

    Muñoz-Yáñez, C; Pérez-Morales, R; Moreno-Macías, H; Calleros-Rincón, E; Ballesteros, G; González, R A; Espinosa, J

    2016-01-01

    Concerning the genetic factors of obesity, no consistent association between populations has been reported, which may be due to the frequency of polymorphisms, the lifestyle of studied populations and its interaction with other factors. We studied a possible association of polymorphisms FTO rs9939609, PPARG rs1801282, and ADIPOQ rs4632532 and rs182052 with obesity phenotypes in 215 Mexican children. Glucose, triglycerides, cholesterol, HDL and LDL were measured. In addition, weight, height, waist circumference and triceps skin thickness were recorded. High-energy diets and sedentary behavior were evaluated with a validated questionnaire. In contrast with other reports, only FTO rs9939609 was associated with obesity related-traits, including BMI (p = 0.03), waist circumference (p = 0.02), triceps skinfold (p = 0.03) and waist/height ratio (p = 0.01), and also with cholesterol levels (p = 0.02) and LDL (p = 0.009). Lower levels of triglycerides (p=0.04) were related with presence of PPARG rs1801282, while ADIPOQ rs4632532 showed an effect on HDL (p = 0.03) levels. On the other hand, diet, physical activity and screen time were not related with obesity. In summary, only FTO rs9939609 was associated with obesity related-traits, while PPARG2 rs1801282 and ADIPOQ rs4632532 were involved in lipid metabolism.

  5. Polymorphisms FTO rs9939609, PPARG rs1801282 and ADIPOQ rs4632532 and rs182052 but not lifestyle are associated with obesity related-traits in Mexican children

    PubMed Central

    Muñoz-Yáñez, C; Pérez-Morales, R; Moreno-Macías, H; Calleros-Rincón, E; Ballesteros, G; González, R. A; Espinosa, J

    2016-01-01

    Abstract Concerning the genetic factors of obesity, no consistent association between populations has been reported, which may be due to the frequency of polymorphisms, the lifestyle of studied populations and its interaction with other factors. We studied a possible association of polymorphisms FTO rs9939609, PPARG rs1801282, and ADIPOQ rs4632532 and rs182052 with obesity phenotypes in 215 Mexican children. Glucose, triglycerides, cholesterol, HDL and LDL were measured. In addition, weight, height, waist circumference and triceps skin thickness were recorded. High-energy diets and sedentary behavior were evaluated with a validated questionnaire. In contrast with other reports, only FTO rs9939609 was associated with obesity related-traits, including BMI (p = 0.03), waist circumference (p = 0.02), triceps skinfold (p = 0.03) and waist/height ratio (p = 0.01), and also with cholesterol levels (p = 0.02) and LDL (p = 0.009). Lower levels of triglycerides (p=0.04) were related with presence of PPARG rs1801282, while ADIPOQ rs4632532 showed an effect on HDL (p = 0.03) levels. On the other hand, diet, physical activity and screen time were not related with obesity. In summary, only FTO rs9939609 was associated with obesity related-traits, while PPARG2 rs1801282 and ADIPOQ rs4632532 were involved in lipid metabolism. PMID:27560839

  6. Maternal Overweight Programs Insulin and Adiponectin Signaling in the Offspring

    PubMed Central

    Shankar, Kartik; Kang, Ping; Harrell, Amanda; Zhong, Ying; Marecki, John C.; Ronis, Martin J. J.; Badger, Thomas M.

    2010-01-01

    Gestational exposure to maternal overweight (OW) influences the risk of obesity in adult life. Male offspring from OW dams gain greater body weight and fat mass and develop insulin resistance when fed high-fat diets (45% fat). In this report, we identify molecular targets of maternal OW-induced programming at postnatal d 21 before challenge with the high-fat diet. We conducted global transcriptome profiling, gene/protein expression analyses, and characterization of downstream signaling of insulin and adiponectin pathways in conjunction with endocrine and biochemical characterization. Offspring born to OW dams displayed increased serum insulin, leptin, and resistin levels (P < 0.05) at postnatal d 21 preceding changes in body composition. A lipogenic transcriptome signature in the liver, before development of obesity, was evident in OW-dam offspring. A coordinated locus of 20 sterol regulatory element-binding protein-1-regulated target genes was induced by maternal OW. Increased nuclear levels of sterol regulatory element-binding protein-1 and recruitment to the fatty acid synthase promoter were confirmed via ELISA and chromatin immunoprecipitation analyses, respectively. Higher fatty acid synthase and acetyl coenzyme A carboxylase protein and pAKT (Thr308) and phospho-insulin receptor-β were confirmed via immunoblotting. Maternal OW also attenuated AMP kinase/peroxisome proliferator-activated receptor-α signaling in the offspring liver, including transcriptional down-regulation of several peroxisome proliferator-activated receptor-α-regulated genes. Hepatic mRNA and circulating fibroblast growth factor-21 levels were significantly lower in OW-dam offspring. Furthermore, serum levels of high-molecular-weight adiponectin (P < 0.05) were decreased in OW-dam offspring. Phosphorylation of hepatic AMP-kinase (Thr172) was significantly decreased in OW-dam offspring, along with lower AdipoR1 mRNA. Our results strongly suggest that gestational exposure to maternal

  7. Delayed liver regeneration after partial hepatectomy in adiponectin knockout mice

    SciTech Connect

    Ezaki, Hisao; Yoshida, Yuichi; Saji, Yukiko; Takemura, Takayo; Fukushima, Juichi; Matsumoto, Hitoshi; Kamada, Yoshihiro; Wada, Akira; Igura, Takumi; Kihara, Shinji; Funahashi, Tohru; Shimomura, Iichiro; Tamura, Shinji; Kiso, Shinichi Hayashi, Norio

    2009-01-02

    We previously demonstrated that adiponectin has anti-fibrogenic and anti-inflammatory effects in the liver of mouse models of various liver diseases. However, its role in liver regeneration remains unclear. The aim of this study was to determine the role of adiponectin in liver regeneration. We assessed liver regeneration after partial hepatectomy in wild-type (WT) and adiponectin knockout (KO) mice. We analyzed DNA replication and various signaling pathways involved in cell proliferation and metabolism. Adiponectin KO mice exhibited delayed DNA replication and increased lipid accumulation in the regenerating liver. The expression levels of peroxisome proliferator-activated receptor (PPAR) {alpha} and carnitine palmitoyltransferase-1 (CPT-1), a key enzyme in mitochondrial fatty acid oxidation, were decreased in adiponectin KO mice, suggesting possible contribution of altered fat metabolism to these phenomena. Collectively, the present results highlight a new role for adiponectin in the process of liver regeneration.

  8. Adiponectin and end-stage renal disease.

    PubMed

    Markaki, Anastasia; Psylinakis, Emmanuel; Spyridaki, Aspasia

    2016-07-01

    Adiponectin (ADPN) is an adipokine with significant anti-inflammatory, insulin-sensitizing and anti-atherogenic properties, which is generally associated with a beneficial cardiometabolic profile. Paradoxically, end-stage renal disease (ESRD) is characterized by markedly increased plasma ADPN levels and increased cardiovascular risk. In spite of the cardioprotective properties attributed to adiponectin, cardiovascular complications remain the main cause of mortality in the ESRD population. Furthermore, these patients have enhanced chronic inflammation, increased insulin resistance and persistent protein-energy wasting. Studies of the impact of ADPN on clinical outcomes among ESRD patients have so far yielded contradictory results. This review article summarizes the current knowledge on ADPN functions and explores the role of ADPN in ESRD patients, with specific focus on inflammation, insulin resistance, cardiovascular disease and wasting.

  9. Globular adiponectin induces a pro-inflammatory response in human astrocytic cells.

    PubMed

    Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana; Klegeris, Andis; Little, Jonathan P

    2014-03-28

    Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer's disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observed link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes.

  10. Energy homeostasis genes and breast cancer risk: The influence of ancestry, body size, and menopausal status, the breast cancer health disparities study

    PubMed Central

    Slattery, Martha L.; Lundgreen, Abbie; Hines, Lisa; Wolff, Roger K.; Torres-Mejia, Gabriella; Baumgartner, Kathy N.; John, Esther M.

    2015-01-01

    Background Obesity and breast cancer risk is multifaceted and genes associated with energy homeostasis may modify this relationship. Methods We evaluated 10 genes that have been associated with obesity and energy homeostasis to determine their association with breast cancer risk in Hispanic/Native American (2111 cases, 2597 controls) and non-Hispanic white (1481 cases, 1585 controls) women. Results Cholecystokinin (CCK) rs747455 and proopiomelanocortin (POMC) rs6713532 and rs7565877 (for low Indigenous American (IA) ancestry); CCK rs8192472 and neuropeptide Y (NYP) rs16141 and rs14129 (intermediate IA ancestry); and leptin receptor (LEPR) rs11585329 (high IA ancestry) were strongly associated with multiple indicators of body size. There were no significant associations with breast cancer risk between genes and SNPs overall. However, LEPR was significantly associated with breast cancer risk among women with low IA ancestry (PARTP = 0.024); POMC was significantly associated with breast cancer risk among women with intermediate (PARTP = 0.015) and high (PARTP = 0.012) IA ancestry. The overall pathway was statistically significant for pre-menopausal women with low IA ancestry (PARTP = 0.05), as was cocaine and amphetamine regulated transcript protein (CARTPT) (PARTP = 0.014) and ghrelin (GHRL) (PARTP = 0.007). POMC was significantly associated with breast cancer risk among post-menopausal women with higher IA ancestry (PARTP = 0.005). Three SNPs in LEPR (rs6704167, rs17412175, and rs7626141), and adiponectin (ADIPOQ); rs822391) showed significant 4-way interactions (GxExMenopausexAncestry) for multiple indicators of body size among pre-menopausal women. Conclusions Energy homeostasis genes were associated with breast cancer risk; menopausal status, body size, and genetic ancestry influenced this relationship. PMID:26395295

  11. Characterization of the weak calcium binding of trimeric globular adiponectin.

    PubMed

    Yu, Dongmei; Zhang, Chao; Wang, Han; Qin, Peiwu

    2013-06-01

    Adiponectin is secreted from adipose tissue and functions as a protein hormone in regulating glucose metabolism and fatty acid catabolism. Adiponectin plays an important role as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. Crystal structures of globular adiponectin have been resolved with three calcium-binding sites on the top of its central tunnel. However, the calcium-binding property of adiponectin remains elusive. Mouse globular adiponectin was cloned into pET11a and expressed in Escherichia coli. The folding of adiponectin was indicated by the spread of resonances in HSQC spectrum. Luminescence resonance energy transfer was used to obtain the binding constant (K(d)) of Tb(3+) and the inhibitor constant (K(i)) of Ca(2+) for globular adiponectin. The obtained calcium-binding affinity to adiponectin is relatively low (~2 mM), which indicates that the high concentration of adiponectin in circulating system may function as calcium storage bank and buffer the free calcium concentration.

  12. Enhanced Metabolic Flexibility Associated with Elevated Adiponectin Levels

    PubMed Central

    Asterholm, Ingrid Wernstedt; Scherer, Philipp E.

    2010-01-01

    Metabolically healthy individuals effectively adapt to changes in nutritional state. Here, we focus on the effects of the adipocyte-derived secretory molecule adiponectin on adipose tissue in mouse models with genetically altered adiponectin levels. We found that higher adiponectin levels increased sensitivity to the lipolytic effects of adrenergic receptor agonists. In parallel, adiponectin-overexpressing mice also display enhanced clearance of circulating fatty acids and increased expansion of subcutaneous adipose tissue with chronic high fat diet (HFD) feeding. These adaptive changes to the HFD were associated with increased mitochondrial density in adipocytes, smaller adipocyte size, and a general transcriptional up-regulation of factors involved in lipid storage through efficient esterification of free fatty acids. The physiological response to adiponectin overexpression resembles in many ways the effects of chronic exposure to β3-adrenergic agonist treatment, which also results in improvements in insulin sensitivity. In addition, using a novel computed tomography-based method for measurements of hepatic lipids, we resolved the temporal events taking place in the liver in response to acute HFD exposure in both wild-type and adiponectin-overexpressing mice. Increased levels of adiponectin potently protect against HFD-induced hepatic lipid accumulation and preserve insulin sensitivity. Given these profound effects of adiponectin, we propose that adiponectin is a factor that increases the metabolic flexibility of adipose tissue, enhancing its ability to maintain proper function under metabolically challenging conditions. PMID:20093494

  13. Effect of diet on adiponectin levels in blood.

    PubMed

    Silva, Flávia M; de Almeida, Jussara C; Feoli, Ana M

    2011-10-01

    Dietary management has been considered an alternative means of modulating adiponectin levels. The purpose of this review is to examine the scientific evidence regarding the effect of diet on adiponectin levels in blood. Clinical trials were selected from Medline until April 2010 using the following MeSH terms: adipokines OR adiponectin AND diet OR lifestyle. A total of 220 articles were identified in the initial search, and 52 studies utilizing three different methods of dietary management were included in the present review: low-calorie diets (n = 9 studies), modification of diet composition (n = 33), and diet plus exercise (n = 10). Daily intake of fish or omega-3 supplementation increased adiponectin levels by 14-60%. Weight loss achieved with a low-calorie diet plus exercise increased adiponectin levels in the range of 18-48%. A 60-115% increase in adiponectin levels was obtained with fiber supplementation. In conclusion, dietary management can be an effective therapeutic means of increasing adiponectin levels. Studies investigating different forms of adiponectin and changes in the types of adipose tissue are necessary in order to elucidate the mechanisms involved in the modulation of adiponectin levels.

  14. Crystal structures of the human adiponectin receptors

    PubMed Central

    Tanabe, Hiroaki; Fujii, Yoshifumi; Hosaka, Toshiaki; Motoyama, Kanna; Ikeda, Mariko; Wakiyama, Motoaki; Terada, Takaho; Ohsawa, Noboru; Hato, Masakatsu; Ogasawara, Satoshi; Hino, Tomoya; Murata, Takeshi; Iwata, So; Hirata, Kunio; Kawano, Yoshiaki; Yamamoto, Masaki; Kimura-Someya, Tomomi; Shirouzu, Mikako; Yamauchi, Toshimasa; Kadowaki, Takashi; Yokoyama, Shigeyuki

    2015-01-01

    Adiponectin stimulation of its receptors, AdipoR1 and AdipoR2, increases AMPK and PPAR activities, respectively, thereby contributing to healthy longevity as key anti-diabetic molecules. AdipoR1 and AdipoR2 were predicted to contain seven transmembrane helices with the opposite topology to G protein-coupled receptor (GPCR)s. Here we report the crystal structures of human AdipoR1 and AdipoR2 at 2.9- and 2.4-Å resolution, respectively, which represent a novel class of receptor structure. The seven-transmembrane helices, conformationally distinct from those of GPCRs, enclose a large cavity where three conserved histidine residues coordinate a zinc ion. The zinc-binding structure may play a role in the adiponectin-stimulated AMPK phosphorylation and UCP2 upregulation. Adiponectin may broadly interact with the extracellular face, rather than the C-terminal flexible tail, of the receptors. The present information will facilitate the understanding of novel structure-function relationships and the development and optimization of AdipoR agonists for the treatment of obesity-related diseases, such as type 2 diabetes. PMID:25855295

  15. Angiotensin-converting enzyme (ACE) inhibitors modulate cellular retinol-binding protein 1 and adiponectin expression in adipocytes via the ACE-dependent signaling cascade.

    PubMed

    Kohlstedt, Karin; Gershome, Cynthia; Trouvain, Caroline; Hofmann, Wolf-Karsten; Fichtlscherer, Stephan; Fleming, Ingrid

    2009-03-01

    Inhibitors of the angiotensin-converting enzyme (ACE) decrease angiotensin II production and activate an intracellular signaling cascade that affects gene expression in endothelial cells. Because ACE inhibitors have been reported to delay the onset of type 2 diabetes, we determined ACE signaling-modulated gene expression in endothelial cells and adipocytes. Using differential gene expression analysis, several genes were identified that were 3-fold up- or down-regulated by ramiprilat in cells expressing wild-type ACE versus cells expressing a signaling-dead ACE mutant. One up-regulated gene was the cellular retinol-binding protein 1 (CRBP1). In adipocytes, the overexpression of CRBP1 enhanced (4- to 5-fold) the activity of promoters containing response elements for retinol-dependent nuclear receptors [retinoic acid receptor (RAR) and retinoid X receptor (RXR)] or peroxisome proliferator-activated receptors (PPAR). CRBP1 overexpression also enhanced the promoter activity (by 470 +/- 40%) and expression/release of the anti-inflammatory and antiatherogenic adipokine adiponectin (cellular adiponectin by 196 +/- 24%, soluble adiponectin by 228 +/- 74%). Significantly increased adiponectin secretion was also observed after ACE inhibitor treatment of human preadipocytes, an effect prevented by small interfering RNA against CRBP1. Furthermore, in ob/ob mice, ramipril markedly potentiated both the basal (approximately 2-fold) and rosiglitazonestimulated circulating levels of adiponectin. In patients with coronary artery disease or type 2 diabetes, ACE inhibition also significantly increased plasma adiponectin levels (1.6- or 2.1-fold, respectively). In summary, ACE inhibitors affect adipocyte homeostasis via CRBP1 through the activation of RAR/RXR-PPAR signaling and up-regulation of adiponectin. The latter may contribute to the beneficial effects of ACE inhibitors on the development of type 2 diabetes in patients with an activated renin-angiotensin system.

  16. Longitudinal changes in adipose tissue of dairy cows from late pregnancy to lactation. Part 2: The SIRT-PPARGC1A axis and its relationship with the adiponectin system.

    PubMed

    Weber, M; Locher, L; Huber, K; Rehage, J; Tienken, R; Meyer, U; Dänicke, S; Webb, L; Sauerwein, H; Mielenz, M

    2016-02-01

    The transition period in dairy cows is characterized by major changes in glucose and adipose tissue metabolism. The Sirtuin-1 (SIRT1) PPARγ co-activator 1α (PPARGC1A) axis might be related to the adiponectin (ADIPOQ) system to orchestrate the regulation of these processes. We aimed to assess the mRNA abundance of the aforementioned components in one visceral and one subcutaneous fat depot, together with the ADIPOQ concentrations in serum of dairy cows from late gestation to early lactation. In addition, the effect of 2 diets differing in energy density was tested. Twenty pluriparous German Holstein cows were all kept on the same silage-based diet until d 42 antepartum. From then on until d 1 antepartum, 10 animals each were assigned to either high-concentrate (60:40 concentrate:roughage) or low-concentrate (30:70) diets. Both groups were further subdivided into a control and a niacin group, the latter receiving 24 g/d nicotinic acid from d -42 until d 24. From d 1 postpartum (p.p.) to d 24 p.p., the concentrate portion was increased from 30 to 50% for all cows. Biopsies of subcutaneous (SCAT) and retroperitoneal adipose tissue (RPAT) were taken at d -42, 1, 21, and 100 relative to parturition. Blood samples were drawn along with the biopsies as well as on d -21, -14, -7, -3, 1, 3, 7, 14, 21, 28, 35, 42, 63, 82, and 100 relative to calving. Quantification of target mRNA was done using quantitative PCR and serum ADIPOQ concentration was measured via ELISA. The feeding regimen did not affect the variables examined. Serum ADIPOQ concentrations decreased toward parturition, returned to precalving levels within 1 wk after parturition, and remained on a constant level until the end of the experiment. The mRNA abundance of SIRT1, PPARGC1A, NAMPT, and the ADIPOQ receptors 1 (ADIPOR1) and 2 (ADIPOR2) changed in SCAT and RPAT during the considered time period. Comparing SCAT and RPAT, the mRNA of SIRT1, ADIPOR1, and ADIPOR2 were more abundant in RPAT, whereas PPARGC1A and

  17. Adiponectin is partially associated with exosomes in mouse serum.

    PubMed

    Phoonsawat, Worrawalan; Aoki-Yoshida, Ayako; Tsuruta, Takeshi; Sonoyama, Kei

    2014-06-06

    Exosomes are membrane vesicles 30-120 nm in diameter that are released by many cell types and carry a cargo of proteins, lipids, mRNA, and microRNA. Cultured adipocytes reportedly release exosomes that may play a role in cell-to-cell communication during the development of metabolic diseases. However, the characteristics and function of exosomes released from adipocytes in vivo remain to be elucidated. Clearly, adipocyte-derived exosomes could exist in the circulation and may be associated with adipocyte-specific proteins such as adipocytokines. We isolated exosomes from serum of mice by differential centrifugation and analyzed adiponectin, leptin, and resistin in the exosome fraction. Western blotting detected adiponectin but no leptin and only trace amounts of resistin in the exosome fraction. The adiponectin signal in the exosome fraction was decreased by proteinase K treatment and completely quenched by a combination of proteinase K and Triton X-100. Quantitative ELISA showed that the exosome fraction contains considerable amounts of adiponectin, but not leptin or resistin. The concentration of adiponectin in the serum and the ratio of adiponectin to total protein in the exosome fraction were lower in obese mice than in lean mice. These results suggest that a portion of adiponectin exists as a transmembrane protein in the exosomes in mouse serum. We propose adiponectin as a marker of exosomes released from adipocytes in vivo.

  18. T-cadherin Is Essential for Adiponectin-mediated Revascularization*

    PubMed Central

    Parker-Duffen, Jennifer L.; Nakamura, Kazuto; Silver, Marcy; Kikuchi, Ryosuke; Tigges, Ulrich; Yoshida, Sumiko; Denzel, Martin S.; Ranscht, Barbara; Walsh, Kenneth

    2013-01-01

    Adipose tissue secretes protein factors that have systemic actions on cardiovascular tissues. Previous studies have shown that ablation of the adipocyte-secreted protein adiponectin leads to endothelial dysfunction, whereas its overexpression promotes wound healing. However, the receptor(s) mediating the protective effects of adiponectin on the vasculature is not known. Here we examined the role of membrane protein T-cadherin, which localizes adiponectin to the vascular endothelium, in the revascularization response to chronic ischemia. T-cadherin-deficient mice were analyzed in a model of hind limb ischemia where blood flow is surgically disrupted in one limb and recovery is monitored over 28 days by laser Doppler perfusion imaging. In this model, T-cadherin-deficient mice phenocopy adiponectin-deficient mice such that both strains display an impaired blood flow recovery compared with wild-type controls. Delivery of exogenous adiponectin rescued the impaired revascularization phenotype in adiponectin-deficient mice but not in T-cadherin-deficient mice. In cultured endothelial cells, T-cadherin deficiency by siRNA knockdown prevented the ability of adiponectin to promote cellular migration and proliferation. These data highlight a previously unrecognized role for T-cadherin in limb revascularization and show that it is essential for mediating the vascular actions of adiponectin. PMID:23824191

  19. Aldehyde oxidase 1 is highly abundant in hepatic steatosis and is downregulated by adiponectin and fenofibric acid in hepatocytes in vitro

    SciTech Connect

    Neumeier, Markus; Weigert, Johanna; Schaeffler, Andreas; Weiss, Thomas S.; Schmidl, Christian; Buettner, Roland; Bollheimer, Cornelius; Aslanidis, Charalampos; Schoelmerich, Juergen; Buechler, Christa . E-mail: christa.buechler@klinik.uni-regensburg.de

    2006-11-24

    Adiponectin protects the liver from steatosis caused by obesity or alcohol and therefore the influence of adiponectin on human hepatocytes was analyzed. GeneChip experiments indicated that recombinant adiponectin downregulates aldehyde oxidase 1 (AOX1) expression and this was confirmed by real-time RT-PCR and immunoblot. AOX1 is a xenobiotic metabolizing protein and produces reactive oxygen species (ROS), that promote cell damage and fibrogenesis. Adiponectin and fenofibric acid activate peroxisome proliferator-activated receptor-{alpha} (PPAR-{alpha}) and both suppress AOX1 protein and this is blocked by the PPAR-{alpha} antagonist RU486. Obesity is associated with low adiponectin, reduced hepatic PPAR-{alpha} activity and fatty liver, and AOX1 was found induced in the liver of rats on a high-fat diet when compared to controls. Free fatty acids and leptin, that are elevated in obesity, failed to upregulate AOX1 in vitro. The current data indicate that adiponectin reduces AOX1 by activating PPAR-{alpha} whereas fatty liver disease is associated with elevated hepatic AOX1. High AOX1 may be associated with higher ROS well described to induce fibrogenesis in liver tissue but may also influence drug metabolism and activity.

  20. White Adipocyte Adiponectin Exocytosis Is Stimulated via β3-Adrenergic Signaling and Activation of Epac1: Catecholamine Resistance in Obesity and Type 2 Diabetes.

    PubMed

    Komai, Ali M; Musovic, Saliha; Peris, Eduard; Alrifaiy, Ahmed; El Hachmane, Mickaël F; Johansson, Marcus; Wernstedt Asterholm, Ingrid; Olofsson, Charlotta S

    2016-11-01

    We investigated the physiological regulation of adiponectin exocytosis in health and metabolic disease by a combination of membrane capacitance patch-clamp recordings and biochemical measurements of short-term (30-min incubations) adiponectin secretion. Epinephrine or the β3-adrenergic receptor (AR) agonist CL 316,243 (CL) stimulated adiponectin exocytosis/secretion in cultured 3T3-L1 and in primary subcutaneous mouse adipocytes, and the stimulation was inhibited by the Epac (Exchange Protein directly Activated by cAMP) antagonist ESI-09. The β3AR was highly expressed in cultured and primary adipocytes, whereas other ARs were detected at lower levels. 3T3-L1 and primary adipocytes expressed Epac1, whereas Epac2 was undetectable. Adiponectin secretion could not be stimulated by epinephrine or CL in adipocytes isolated from obese/type 2 diabetic mice, whereas the basal (unstimulated) adiponectin release level was elevated twofold. Gene expression of β3AR and Epac1 was reduced in adipocytes from obese animals, and corresponded to a respective ∼35% and ∼30% reduction at the protein level. Small interfering RNA-mediated knockdown of β3AR (∼60%) and Epac1 (∼50%) was associated with abrogated catecholamine-stimulated adiponectin secretion. We propose that adiponectin exocytosis is stimulated via adrenergic signaling pathways mainly involving β3ARs. We further suggest that adrenergically stimulated adiponectin secretion is disturbed in obesity/type 2 diabetes as a result of the reduced expression of β3ARs and Epac1 in a state we define as "catecholamine resistance."

  1. Activation of AMPK by berberine promotes adiponectin multimerization in 3T3-L1 adipocytes.

    PubMed

    Li, Yun; Wang, Pengcheng; Zhuang, Yuan; Lin, Huan; Li, Yehua; Liu, Ling; Meng, Qinghang; Cui, Ting; Liu, Jing; Li, Zhen

    2011-06-23

    Adiponectin is assembled into trimer (LMW), hexamer (MMW) and high-molecular-weight (HMW) multimer in adipocytes. The HMW adiponectin is more metabolically active and closely associated with peripheral insulin sensitivity. In this study, we reported that berberine, an isoquinoline alkaloid with insulin-sensitizing effect, inhibits the expression of adiponectin, but promotes the assembly of HMW adiponectin and increases the ratio of HMW to total adiponectin. Berberine activates AMPK. Knockdown of AMPKα1 abolishes the effect of berberine. Activation of AMPK by AICAR also increases the level of HMW adiponectin. Our study suggested that activation of AMPK by berberine promotes adiponectin multimerization.

  2. Role of adiponectin in insulin-resistant hypertension and atherosclerosis.

    PubMed

    Murakami, Hideyuki; Ura, Nobuyuki; Furuhashi, Masato; Higashiura, Katsuhiro; Miura, Tetsuji; Shimamoto, Kazuaki

    2003-09-01

    Insulin resistance is one of the major risk factors associated with development of hypertension and atherosclerosis. Recent studies have shown that adiponectin, an adipocyte-derived hormone, may be involved in insulin resistance and development of atherosclerosis in diabetes patients. The aim of this study was to examine adiponectin levels in patients with essential hypertension to determine the relationships between adiponectin levels and insulin sensitivity and to examine the relationship of adiponectin with pulse wave velocity (PWV) in a general population based on the results of an epidemiological survey in Japan. In a clinical study, 20 normotensives (NT) and 30 non-treated essential hypertensives (EHT) were hospitalized, and euglycemic hyperinsulinemic glucose clamp (GC) was performed to evaluate insulin sensitivity defined as M value. EHT were divided into insulin-resistant EHT (EHT-R) and insulin-nonresistant EHT (EHT-N) according to the mean -1 SD of the M value of NT as a cut-off point. Fasting plasma glucose (FPG), immunoreactive insulin (IRI), and adiponectin concentrations were measured. There were no significant differences in body mass index (BMI) or FPG among the NT, EHT-N, and EHT-R groups. The M value and adiponectin concentration in EHT-R were significantly lower than those in the NT or EHT-N. The IRI level in the EHT-R was significantly higher than those in the other groups. A positive correlation between adiponectin concentration and M value was found in all subjects, and adiponectin concentration and M value were found to be significant determinants of each other in multiple regression analysis. In an epidemiological study, we studied 391 male inhabitants of rural communities in Hokkaido, Japan. Systolic blood pressure (SBP), BMI, FPG, IRI, and adiponectin were measured in all subjects early in the morning. Homeostasis model assessment (HOMA) values were calculated as an index of insulin sensitivity, and PWV was used as an index of

  3. Characteristics and potential functions of human milk adiponectin.

    PubMed

    Newburg, David S; Woo, Jessica G; Morrow, Ardythe L

    2010-02-01

    Adiponectin is a protein hormone produced by adipose tissue, whose circulating levels are inversely related to adiposity and inflammation. Adiponectin circulates as oligomers, from the low-molecular-weight trimer to the high-molecular-weight octodecamer (18 mer). Each oligomer has distinct biological activities, which include enhancement of insulin sensitivity and metabolic control and suppression of inflammation. Adiponectin occurs in human milk at higher concentrations than leptin. The adiponectin in human milk is almost entirely of the high-molecular-weight form, the form with the highest activity in controlling many types of metabolic processes. Human adiponectin fed to infant mice is transported across the intestinal mucosa into the serum. An inverse relationship between adiponectin levels in milk and adiposity (weight-for-height) of the breast-fed infant was observed and could be due to modulation of infant metabolism by milk adiponectin and may be related to the observed protection against obesity by breast-feeding. Human milk may be a medium whereby the hormonal milieu (in response to internal factors and the environment) of the mother can be used to communicate with the breast-fed infant to modify infant metabolic processes. Transmission of information from mother to infant through milk may allow adaptation to fluctuating environmental conditions.

  4. Evaluation of salivary adiponectin profile in obese patients.

    PubMed

    Nigro, E; Piombino, P; Scudiero, O; Monaco, M L; Schettino, P; Chambery, A; Daniele, A

    2015-01-01

    Obesity is a chronic inflammatory disease significantly risen worldwide, especially among children. Adipokines, secreted from adipose tissue, are hormones involved in various cellular processes such as energy metabolism and inflammation. Among the others, adiponectin is gaining increasing interest for its insulin-sentitizing, anti-atherogenic and anti-inflammatory properties. This adipokine undergoes different post-translational modifications, after which it circulates as oligomers of high, medium and low molecular weight (HMW, MMW, LMW); HMW are the most biologically active oligomers. Serum adiponectin levels as well as the amount of its oligomers are inversely correlated to BMI and closely associated with obesity and related diseases. In this study, we analyzed total adiponectin expression and its oligomeric profile in saliva samples from 27 obese compared to 27 age- and sex-matched controls. Moreover, we compared adiponectin oligomerization between serum and saliva samples. The analysis of the different adiponectin oligomers reveals a slightly higher expression of total, HMW and LMW salivary adiponectin in obese patients compared to controls. Finally, FPLC analysis evidenced that HMW oligomers in saliva have a higher molecular weight than in serum confirming the presence of more complex oligomers in saliva, previously identified as super HMW (S-HMW). Saliva is considered a potential source of novel biomarkers for the diagnosis of metabolic disorders. The assessment of total adiponectin and its oligomeric profiles in saliva samples may represent a promising biological marker for the analysis of metabolic diseases.

  5. Adiponectin signaling and function in insulin target tissues

    PubMed Central

    Ruan, Hong; Dong, Lily Q.

    2016-01-01

    Obesity-linked type 2 diabetes is one of the paramount causes of morbidity and mortality worldwide, posing a major threat on human health, productivity, and quality of life. Despite great progress made towards a better understanding of the molecular basis of diabetes, the available clinical counter-measures against insulin resistance, a defect that is central to obesity-linked type 2 diabetes, remain inadequate. Adiponectin, an abundant adipocyte-secreted factor with a wide-range of biological activities, improves insulin sensitivity in major insulin target tissues, modulates inflammatory responses, and plays a crucial role in the regulation of energy metabolism. However, adiponectin as a promising therapeutic approach has not been thoroughly explored in the context of pharmacological intervention, and extensive efforts are being devoted to gain mechanistic understanding of adiponectin signaling and its regulation, and reveal therapeutic targets. Here, we discuss tissue- and cell-specific functions of adiponectin, with an emphasis on the regulation of adiponectin signaling pathways, and the potential crosstalk between the adiponectin and other signaling pathways involved in metabolic regulation. Understanding better just why and how adiponectin and its downstream effector molecules work will be essential, together with empirical trials, to guide us to therapies that target the root cause(s) of type 2 diabetes and insulin resistance. PMID:26993044

  6. Regulation of adiponectin receptor 1 in human hepatocytes by agonists of nuclear receptors

    SciTech Connect

    Neumeier, Markus; Weigert, Johanna; Schaeffler, Andreas; Weiss, Thomas; Kirchner, Stefan; Laberer, Sabine; Schoelmerich, Juergen; Buechler, Christa . E-mail: christa.buechler@klinik.uni-regensburg.de

    2005-09-02

    The adiponectin receptors AdipoR1 and AdipoR2 have been identified to mediate the insulin-sensitizing effects of adiponectin. Although AdipoR2 was suggested to be the main receptor for this adipokine in hepatocytes, AdipoR1 protein is highly abundant in primary human hepatocytes and hepatocytic cell lines. Nuclear receptors are main regulators of lipid metabolism and activation of peroxisome proliferator-activated receptor {alpha} and {gamma}, retinoid X receptor (RXR), and liver X receptor (LXR) by specific ligands may influence AdipoR1 abundance. AdipoR1 protein is neither altered by RXR or LXR agonists nor by pioglitazone. In contrast, fenofibric acid reduces AdipoR1 whereas hepatotoxic troglitazone upregulates AdipoR1 protein in HepG2 cells. Taken together this work shows for the first time that AdipoR1 protein is expressed in human hepatocytes but that it is not a direct target gene of nuclear receptors. Elevated AdipoR1 induced by hepatotoxic troglitazone may indicate a role of this receptor in adiponectin-mediated beneficial effects in liver damage.

  7. Changes of adiponectin oligomer composition by moderate weight reduction.

    PubMed

    Bobbert, Thomas; Rochlitz, Helmut; Wegewitz, Uta; Akpulat, Suzan; Mai, Knut; Weickert, Martin O; Möhlig, Matthias; Pfeiffer, Andreas F H; Spranger, Joachim

    2005-09-01

    Adiponectin affects lipid metabolism and insulin sensitivity. However, adiponectin circulates in three different oligomers that may also have distinct biological functions. We aimed to analyze the role of these oligomers in obesity and lipid metabolism after weight reduction. A total of 17 obese volunteers (15 women and 2 men) participated in a weight reduction program. Individuals were characterized before and after 6 months of a balanced diet. Adiponectin was determined by enzyme-linked immunosorbent assay, and oligomers were detected by nondenaturating Western blot. BMI decreased (35.1 +/- 1.2 to 32.8 +/- 1.1 kg/m(2), P < 0.001), which was associated with an improved metabolite profile. Total adiponectin increased from 5.3 +/- 0.5 to 6.1 +/- 0.6 microg/ml (P = 0.076). High (HMW) and medium molecular weight (MMW) adiponectin oligomers significantly increased during weight reduction (HMW: 0.37 +/- 0.07 to 0.4 +/- 0.08 microg/ml, P = 0.042; MMW: 2.3 +/- 0.2 to 2.9 +/- 0.3 microg/ml, P = 0.007), while low molecular weight (LMW) did not significantly change. Body weight inversely correlated with HMW (r = -0.695, P = 0.002) and positively with LMW (r = 0.579, P = 0.015). Interestingly, HDL cholesterol and HMW were strongly correlated (r = 0.665, P = 0.007). Indeed, HMW and free fatty acids before weight reduction predicted approximately 60% of HDL changes during intervention. In conclusion, weight reduction results in a relative increase of HMW/MMW adiponectin and a reduction of LMW adiponectin. Total adiponectin and especially HMW adiponectin are related to circulating HDL cholesterol.

  8. Circulating leptin and adiponectin concentrations in healthy exceptional longevity.

    PubMed

    Pareja-Galeano, Helios; Santos-Lozano, Alejandro; Sanchis-Gomar, Fabian; Fiuza-Luces, Carmen; Garatachea, Nuria; Gálvez, Beatriz G; Lucia, Alejandro; Emanuele, Enzo

    2017-03-01

    People reaching exceptional longevity free of major age-related diseases represent the paradigm of successful aging. Adipose tissue function declines as we age, potentially resulting in changes of circulating adipokines (e.g., leptin and adiponectin). Here, we measured circulating levels of leptin and adiponectin in healthy centenarians (n=81; 100-104 years) and younger elderly controls (n=46; 70-80 years). Centenarians had significant higher serum levels of leptin compared with controls (p<0.001), whereas no significant differences were observed for adiponectin. Further research including also other blood variables will be needed to elucidate whether high leptin levels could serve as a hallmark of healthy exceptional longevity.

  9. Fisetin up-regulates the expression of adiponectin in 3T3-L1 adipocytes via the activation of silent mating type information regulation 2 homologue 1 (SIRT1)-deacetylase and peroxisome proliferator-activated receptors (PPARs).

    PubMed

    Jin, Taewon; Kim, Oh Yoen; Shin, Min-Jeong; Choi, Eun Young; Lee, Sung Sook; Han, Ye Sun; Chung, Ji Hyung

    2014-10-29

    Adiponectin, an adipokine, has been described as showing physiological benefits against obesity-related malfunctions and vascular dysfunction. Several natural compounds that promote the expression and secretion of adipokines in adipocytes could be useful for treating metabolic disorders. This study investigated the effect of fisetin, a dietary flavonoid, on the regulation of adiponectin in adipocytes using 3T3-L1 preadipocytes. The expression and secretion of adiponectin increased in 3T3-L1 cells upon treatment with fisetin in a dose-dependent manner. Fisetin-induced adiponectin secretion was inhibited by peroxisome proliferator-activated receptor (PPAR) antagonists. It was also revealed that fisetin increased the activities of PPARs and silent mating type information regulation 2 homologue 1 (SIRT1) in a dose-dependent manner. Furthermore, the up-regulation of adiponectin and the activation of PPARs induced by fisetin were prevented by a SIRT1 inhibitor. Fisetin also promoted deacetylation of PPAR γ coactivator 1 (PGC-1) and its interaction with PPARs. SIRT knockdown by siRNA significantly decreased both adiponectin production and PPARs-PGC-1 interaction. These results provide evidence that fisetin promotes the gene expression of adiponectin through the activation of SIRT1 and PPARs in adipocytes.

  10. Adiponectin (15-36) stimulates steroidogenic acute regulatory (StAR) protein expression and cortisol production in human adrenocortical cells: role of AMPK and MAPK kinase pathways.

    PubMed

    Ramanjaneya, Manjunath; Conner, Alex C; Brown, James E P; Chen, Jing; Digby, Janet E; Barber, Thomas M; Lehnert, Hendrik; Randeva, Harpal S

    2011-05-01

    Adiponectin is an abundantly circulating adipokine, orchestrating its effects through two 7-transmembrane receptors (AdipoR1 and AdipoR2). Steroidogenesis is regulated by a variety of neuropeptides and adipokines. Earlier studies have reported adipokine mediated steroid production. A key rate-limiting step in steroidogenesis is cholesterol transportation across the mitochondrial membrane by steroidogenic acute regulatory protein (StAR). Several signalling pathways regulate StAR expression. The actions of adiponectin and its role in human adrenocortical steroid biosynthesis are not fully understood. The aim of this study was to investigate the effects of adiponectin on StAR protein expression, steroidogenic genes, and cortisol production and to dissect the signalling cascades involved in the activation of StAR expression. Using qRT-PCR, Western blot analysis and ELISA, we have demonstrated that stimulation of human adrenocortical H295R cells with adiponectin results in increased cortisol secretion. This effect is accompanied by increased expression of key steroidogenic pathway genes including StAR protein expression via ERK1/2 and AMPK-dependent pathways. This has implications for our understanding of adiponectin receptor activation and peripheral steroidogenesis. Finally, our study aims to emphasise the key role of adipokines in the integration of metabolic activity and energy balance partly via the regulation of adrenal steroid production. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.

  11. Perinatal BPA exposure induces hyperglycemia, oxidative stress and decreased adiponectin production in later life of male rat offspring.

    PubMed

    Song, Shunzhe; Zhang, Ling; Zhang, Hongyuan; Wei, Wei; Jia, Lihong

    2014-04-03

    The main object of the present study was to explore the effect of perinatal bisphenol A (BPA) exposure on glucose metabolism in early and later life of male rat offspring, and to establish the potential mechanism of BPA-induced dysglycemia. Pregnant rats were treated with either vehicle or BPA by drinking water at concentrations of 1 and 10 µg/mL BPA from gestation day 6 through the end of lactation. We measured the levels of fasting serum glucose, insulin, adiponectin and parameters of oxidative stress on postnatal day (PND) 50 and PND100 in male offspring, and adiponectin mRNA and protein expression in adipose tissue were also examined. Our results showed that perinatal exposure to 1 or 10 µg/mL BPA induced hyperglycemia with insulin resistance on PND100, but only 10 µg/mL BPA exposure had similar effects as early as PND50. In addition, increased oxidative stress and decreased adiponectin production were also observed in BPA exposed male offspring. Our findings indicated that perinatal exposure to BPA resulted in abnormal glucose metabolism in later life of male offspring, with an earlier and more exacerbated effect at higher doses. Down-regulated expression of adiponectin gene and increased oxidative stress induced by BPA may be associated with insulin resistance.

  12. Regulation of adiponectin in adipocytes upon exposure to HIV-1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV-infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose...

  13. Associations of adiponectin and fertility estimates in Holstein bulls.

    PubMed

    Kasimanickam, Vanmathy R; Kasimanickam, Ramanathan K; Kastelic, John P; Stevenson, Jeffrey S

    2013-03-15

    Adiponectin is a pleiotropic regulator of numerous biological functions, including gonadal steroidogenesis and might play a role in sperm structures and functions. The objectives were to: (1) determine associations among serum concentrations of adiponectin, testosterone, and prolactin, and the sperm DNA fragmentation index; (2) associate sperm adiponectin mRNA abundance with estimates of fertility (sire conception rate); and (3) determine sperm protein expression of adiponectin and its receptor in pre- and postcapacitated sperm from Holstein bulls. In experiment 1, biweekly serum concentrations of adiponectin, prolactin, and testosterone were greater (P < 0.05) for high fertility bulls compared with average and low fertility bulls. Furthermore, sperm DNA fragmentation index was greater (P < 0.05) for low fertility compared with both average and high fertility bulls. In experiment 2, samples of sperm from a single collection from commercial Holstein bulls (N = 34) were used to evaluate relative sperm mRNA expression of adiponectin and its receptors, AdipoR1 and AdipoR2, and protein levels of adiponectin and its receptors, AdipoR1 and AdipoR2, in pre- and postcapacitation sperm. The mRNA abundance of adiponectin and its receptors, AdipoR1 and AdipoR2, were greater for high fertility bulls (>2 to ≤4 sire conception rate) compared with average (≥2 to ≤2) and low (>-2 to ≤-4) fertility bulls. Based on the sperm capacitation assay, average fertility bulls had a greater percentage of acrosome-reacted sperm at 5 hours than high and low fertility bulls, whereas high fertility bulls had a greater percentage of acrosome-reacted sperm than low fertility bulls. After capacitation, levels of adiponectin protein were lower in average fertility bulls, AdipoR1 was lower in all fertility groups, and AdipoR2 was lower in average and high fertility bulls. In conclusion, adiponectin and its receptors had vital roles in sperm structural and functional traits and consequently

  14. Association of adiponectin multimers with Barrett’s oesophagus

    PubMed Central

    Rubenstein, J H; Kao, J Y; Madanick, R D; Zhang, M; Wang, M; Spacek, M B; Donovan, J L; Bright, S D; Shaheen, N J

    2012-01-01

    Objective Barrett’s oesophagus is associated with abdominal obesity. Adiponectin is a peptide that is secreted from adipocytes and circulates in three multimeric forms: low molecular weight (LMW), middle molecular weight (MMW), and high molecular weight (HMW). The anti-inflammatory effects of adiponectin are specific to individual multimers, with LMW being most anti-inflammatory. We postulated that circulating levels of adiponectin and its multimers would be associated with the risk of Barrett’s oesophagus. Design Cross-sectional study. Setting Outpatient clinic in North Carolina, USA. Patients Cases of Barrett’s oesophagus and controls undergoing upper endoscopy for gastro-oesophageal reflux disease (GORD). Main outcome measures Adjusted odds ratios of plasma adiponectin levels and its multimers for Barrett’s oesophagus. Results There were 112 cases of Barrett’s oesophagus and 199 GORD controls. Total adiponectin was not associated with Barrett’s oesophagus (3rd tertile vs 1st tertile adjusted odds ratio (aOR) = 0.88; 95% confidence interval (CI) = 0.44 to 1.78). High levels of LMW adiponectin were associated with a decreased risk of Barrett’s oesophagus (3rd tertile vs 1st tertile aOR = 0.33; 95% CI, 0.16 to 0.69), and a high LMW/total ratio appeared particularly inversely associated with Barrett’s oesophagus (3rd tertile vs 1st tertile aOR = 0.27; 95% CI, 0.13 to 0.58). Conclusions High levels of LMW adiponectin are associated with a decreased risk of Barrett’s oesophagus among patients with GORD. Further human studies are required to confirm these findings, and in vitro studies are needed to understand if there is a mechanism whereby adiponectin may affect Barrett’s metaplasia. PMID:19570765

  15. Potential Neuroprotective Effects of Adiponectin in Alzheimer’s Disease

    PubMed Central

    Ng, Roy Chun-Laam; Chan, Koon-Ho

    2017-01-01

    The adipocyte-secreted protein adiponectin (APN) has several protective functions in the peripheral tissues including insulin sensitizing, anti-inflammatory and anti-oxidative effects that may benefit neurodegenerative diseases such as Alzheimer’s disease (AD). In addition, dysregulation of cerebral insulin sensitivities and signaling activities have been implicated in AD. Emerging insights into the mechanistic roles of adiponectin and AD highlight the potential therapeutic effects for AD through insulin signaling. PMID:28282917

  16. Signaling mechanisms underlying the insulin-sensitizing effects of adiponectin.

    PubMed

    Cheng, Kenneth K Y; Lam, Karen S L; Wang, Baile; Xu, Aimin

    2014-01-01

    Adiponectin is an insulin-sensitizing adipokine with protective effects against a cluster of obesity-related metabolic and cardiovascular disorders. The adipokine exerts its insulin-sensitizing effects by alleviation of obesity-induced ectopic lipid accumulation, lipotoxicity and chronic inflammation, as well as by direct cross-talk with insulin signaling cascades. Adiponectin and insulin signaling pathways converge at the adaptor protein APPL1. On the one hand, APPL1 interacts with adiponectin receptors and mediates both metabolic and vascular actions of adiponectin through activation of AMP-activated protein kinase and p38 MAP kinase. On the other hand, APPL1 potentiates both the actions and secretion of insulin by fine-tuning the Akt activity in multiple insulin target tissues. In obese animals, reduced APPL1 expression contributes to both insulin resistance and defective insulin secretion. This review summarizes recent advances on the molecular mechanisms by which adiponectin sensitizes insulin actions, and discusses the roles of APPL1 in regulating both adiponectin and insulin signaling cascades.

  17. IGFBP-3, hypoxia and TNF-{alpha} inhibit adiponectin transcription

    SciTech Connect

    Zappala, Giovanna; Rechler, Matthew M.

    2009-05-15

    The thiazolidinedione rosiglitazone, an agonist ligand for the nuclear receptor PPAR-{gamma}, improves insulin sensitivity in part by stimulating transcription of the insulin-sensitizing adipokine adiponectin. It activates PPAR-{gamma}-RXR-{alpha} heterodimers bound to PPAR-{gamma} response elements in the adiponectin promoter. Rosiglitazone-stimulated adiponectin protein synthesis in 3T3-L1 mouse adipocytes has been shown to be inhibited by IGFBP-3, which can be induced by hypoxia and the proinflammatory cytokine, TNF-{alpha}, two inhibitors of adiponectin transcription. The present study demonstrates that IGFBP-3, the hypoxia-mimetic agent cobalt chloride, and TNF-{alpha} inhibit rosiglitazone-induced adiponectin transcription in mouse embryo fibroblasts that stably express PPAR-{gamma}2. Native IGFBP-3 can bind RXR-{alpha} and inhibited rosiglitazone stimulated promoter activity, whereas an IGFBP-3 mutant that does not bind RXR-{alpha} did not. These results suggest that IGFBP-3 may mediate the inhibition of adiponectin transcription by hypoxia and TNF-{alpha}, and that IGFBP-3 binding to RXR-{alpha} may be required for the observed inhibition.

  18. Adiponectin and adiponectin receptor system in the rat adrenal gland: ontogenetic and physiologic regulation, and its involvement in regulating adrenocortical growth and steroidogenesis.

    PubMed

    Paschke, Lukasz; Zemleduch, Tomasz; Rucinski, Marcin; Ziolkowska, Agnieszka; Szyszka, Marta; Malendowicz, Ludwik K

    2010-09-01

    Adiponectin (ADN) is a regulatory peptide secreted mostly by adipose tissue and acting via two receptors: AdipoR1 and AdipoR2. Our aim was to investigate expression of adiponectin system genes in the rat adrenal gland as well as its ontogenetic and physiological control. Furthermore, we examined the effects of acute and prolonged activation of HPA axis on ADN system in adipose tissue. By means of QPCR, ADN and AdipoR1 expression was demonstrated in rat adrenal cortex both at mRNA and protein levels, while AdipoR2 could only be detected at mRNA levels. ADN expression level was significantly upregulated in a developing and regenerating adrenal cortex. Globular domain of adiponectin at 10(-9) M stimulated corticosterone output and BrdU incorporation by cultured rat adrenocortical cells. Moreover, both acute (ACTH and ether stress) and prolonged (ACTH) adrenal stimulation resulted in lowered ADN levels, while expression of AdipoR1 and AdipoR2 was upregulated by the acute treatment. Depending on its site of origin, visceral (VAT) or subcutaneous (SAT) adipose tissue responded differently to alterations in HPA axis. VAT expression of ADN and its receptors remained almost unchanged by experimental manipulations. In SAT, on the other hand, expression of ADN and AdipoR2 was markedly increased by ACTH treatment and stress, while dexamethasone suppressed ADN and AdipoR1 mRNA levels. The results of this study provide new evidence for direct and indirect interactions between adipokines and HPA axis.

  19. HCV core-induced nonobese hepatic steatosis is associated with hypoadiponectinemia and is ameliorated by adiponectin administration.

    PubMed

    Chang, Ming-Ling; Yeh, Huei-Chung; Tsou, Yung-Kuan; Wang, Chao-Jan; Cheng, Hsiao-Yang; Sung, Chang-Mu; Ho, Yu-Pin; Chen, Tsung-Hsing; Yeh, Chau-Ting

    2012-07-01

    Obesity-related hepatic steatosis is commonly associated with central fat accumulation and alterations in adipocytokine secretion; however, the connection between nonobese hepatic steatosis and adipocytokines remains unclear. We aim to investigate this connection using an animal model of conditional hepatitis C virus (HCV) core-transgenic mice. Double transgenic mice (DTM) with doxycycline (dox)-regulated hepatic overexpression of the HCV core protein were fed standard rodent chow ad libitum following 1 month of a dox-rich diet. The mice exhibited nonobese hepatic steatosis at 2 months of age. The levels of leptin and adiponectin were assessed in 2-month-old DTM (i.e., HCV core-tetracycline transactivator (tTA)) and single transgenic mice (STM; i.e., tTA). The total fat mass and the body fat distribution of the mice were evaluated using dual-energy X-ray absorptiometry (DEXA) and magnetic resonance imaging (MRI). Microarray analyses and quantitative real-time PCR were conducted using RNA obtained from the visceral fat of paired DTM and STM. Adiponectin was administered intraperitoneally to the 2-month-old DTM. No significant differences of the various fat components were noted between the DTM and STM. Leptin mRNA was downregulated in the visceral fat of DTM (P = 0.011), and serum adiponectin protein levels were reduced in the DTM compared with those in the STM (P = 0.035). Adiponectin treatment also significantly ameliorated hepatic steatosis in the DTM compared to the controls (P = 0.024). In conclusion, HCV core-induced nonobese hepatic steatosis is associated with downregulation of the leptin gene in visceral fat and concurrent hypoadiponectinemia; however, these effects may be ameliorated by adiponectin treatment.

  20. The Effect of Leptin and Adiponectin on KiSS-1 and KissR mRNA Expression in Rat Islets of Langerhans and CRI-D2 Cell Line

    PubMed Central

    Mahmoodzadeh Sagheb, Mandana; Azarpira, Negar; Yaghobi, Ramin

    2014-01-01

    Background: Leptin and adiponectin are the two key metabolic hormones secreted from adipocytes to control food intake and energy expenditure. The action of both hormones in regulation of Gonadotropin Releasing Hormone (GnRH) secretion from the hypothalamus is mediated through Kisspeptins. Kisspeptins are products of KiSS-1 gene. Leptin and adiponectin are modulators of KiSS-1 expression in the hypothalamus. These peptides have also important roles in pancreatic β-cells to control insulin synthesis and secretion and their receptors are detected in Langerhans islets. We hypothesized that leptin and adiponectin might alter KiSS-1 and Kiss Receptor mRNA expression in the islets. Objectives: The aim of this study is to investigate any modulatory effect that leptin and adiponectin may have on the expression of Kiss-1 and KiSSR gene in Langerhans islets. Materials and Methods: We isolated the islets from adult male rats by collagenase and cultured CRI-D2 cell lines to investigate the effect of leptin and adiponectin. Then, we incubated them with different concentrations of leptin and adiponectin for 24 hours. After that, RNA was extracted from the islets and CRI-D2 cells and transcripted to cDNA. KiSS-1 and KissR expression levels were evaluated by real time PCR. Results: In islet and CRI-D2 cells, leptin increased the KiSS-1 mRNA expression significantly, but adiponectin decreased it was expected. Conclusions: These findings indicated the possibility that KiSS-1 mRNA expression is a mediator of leptin and adiponectin function in the islets. PMID:24910643

  1. Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats.

    PubMed

    Rossi, Andrea S; Lombardo, Yolanda B; Lacorte, Jean-Marc; Chicco, Adriana G; Rouault, Christine; Slama, Gérard; Rizkalla, Salwa W

    2005-08-01

    Insulin resistance and adiposity induced by a long-term sucrose-rich diet (SRD) in rats could be reversed by fish oil (FO). Regulation of plasma leptin and adiponectin levels, as well as their gene expression, by FO might be implicated in these findings. This study was designed to evaluate the long-term regulation of leptin and adiponectin by dietary FO in a dietary model of insulin resistance induced by long-term SRD in rats and to determine their impact on adiposity and insulin sensitivity. Rats were randomized to consume a control diet (CD; n = 25) or an SRD (n = 50) for 7 mo. Subsequently, the SRD-fed rats were randomized to consume SRD+FO or to continue on SRD for an additional 2 mo. Long-term SRD induced overweight and decreased both plasma leptin and adiponectin levels without change in gene expression. Dyslipidemia, adiposity, and insulin resistance accompanied these modifications. Shifting the source of fat to FO for 2 mo increased plasma levels of both adipokines, reversed insulin resistance and dyslipidemia, and improved adiposity. These results were not associated with modifications in gene expression. These results suggest that increasing both adipokines by dietary FO might play an essential role in the normalization of insulin resistance and adiposity in dietary-induced, insulin-resistant models.

  2. Cinnamon extract regulates plasma levels of adipose-derived factors and expression of multiple genes related to carbohydrate metabolism and lipogenesis in adipose tissue of fructose-fed rats.

    PubMed

    Qin, B; Polansky, M M; Anderson, R A

    2010-03-01

    We reported earlier that dietary cinnamon extract (CE) improves systemic insulin sensitivity and dyslipidemia by enhancing insulin signaling. In the present study, we have examined the effects of CE on several biomarkers including plasma levels of adipose-derived adipokines, and the potential molecular mechanisms of CE in epididymal adipose tissue (EAT). In Wistar rats fed a high-fructose diet (HFD) to induce insulin resistance, supplementation with a CE (Cinnulin PF, 50 mg/kg daily) for 8 weeks reduced blood glucose, plasma insulin, triglycerides, total cholesterol, chylomicron-apoB48, VLDL-apoB100, and soluble CD36. CE also inhibited plasma retinol binding protein 4 (RBP4) and fatty acid binding protein 4 (FABP4) levels. CE-induced increases in plasma adiponectin were not significant. CE did not affect food intake, bodyweight, and EAT weight. In EAT, there were increases in the insulin receptor ( IR) and IR substrate 2 ( IRS2) mRNA, but CE-induced increases in mRNA expression of IRS1, phosphoinositide-3-kinase, AKT1, glucose transporters 1 and 4 , and glycogen synthase 1 expression and decreased trends in mRNA expression of glycogen synthase kinase 3beta were not statistically significant. CE also enhanced the mRNA levels of ADIPOQ, and inhibited sterol regulatory element binding protein-1c mRNA levels. mRNA and protein levels of fatty acid synthase and FABP4 were inhibited by CE and RBP4, and CD36 protein levels were also decreased by CE. These results suggest that CE effectively ameliorates circulating levels of adipokines partially mediated via regulation of the expression of multiple genes involved in insulin sensitivity and lipogenesis in the EAT.

  3. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells

    SciTech Connect

    Dieudonne, Marie-Noelle; Bussiere, Marianne; Dos Santos, Esther; Leneveu, Marie-Christine; Giudicelli, Yves . E-mail: biochip@wanadoo.fr; Pecquery, Rene

    2006-06-23

    It is well established that obesity is a risk factor for breast cancer and that blood levels of adiponectin, a hormone mainly secreted by white adipocytes, are inversely correlated with the body fat mass. As adiponectin elicits anti-proliferative effects in some cell types, we tested the hypothesis that adiponectin could influence human breast cancer MCF-7 cell growth. Here we show that MCF-7 cells express adiponectin receptors and respond to human recombinant adiponectin by reducing their growth, AMPkinase activation, and p42/p44 MAPkinase inactivation. Further, we demonstrate that the anti-proliferative effect of adiponectin involves activation of cell apoptosis and inhibition of cell cycle. These findings suggest that adiponectin could act in vivo as a paracrine/endocrine growth inhibitor towards mammary epithelial cells. Moreover, adipose adiponectin production being strongly reduced in obesity, this study may help to explain why obesity is a risk factor of developing breast cancers.

  4. Genetic variants in adiponectin and blood pressure responses to dietary sodium or potassium interventions: a family-based association study.

    PubMed

    Chu, C; Wang, Y; Ren, K-Y; Yan, D-Y; Guo, T-S; Zheng, W-L; Yuan, Z-Y; Mu, J-J

    2016-09-01

    Previous studies have shown that genetic factors might have an important role in blood pressure (BP) responses to dietary salt or potassium intake. The aim of this study was to assess the association of common genetic variants of the adiponectin gene with BP responses to controlled dietary sodium or potassium interventions. Subjects (n=334) from 124 families in rural areas of Northern China were recruited. After a 3-day baseline observation, participants sequentially maintained a 7-day low-sodium diet (NaCl, 3 g per day; or sodium, 51.3 mmol per day), followed by a 7-day high-sodium diet (NaCl, 18 g per day; or sodium, 307.8 mmol per day) and a 7-day high-sodium plus potassium supplementation intervention (KCl, 4.5 g per day; or potassium, 60 mmol per day). A total of seven single nucleotide polymorphisms (SNPs) in the adiponectin gene were selected as the study sites. After adjustment for multiple testing, the adiponectin SNP rs16861205 was significantly associated with the diastolic BP (DBP) response to low-salt intervention, and the DBP and mean arterial pressure (MAP) responses to high-salt intervention (P=0.028, 0.023 and 0.027, respectively). SNP rs822394 was associated with the DBP and MAP responses to low-salt intervention and the DBP response to high-salt intervention (P=0.023, 0.030 and 0.033 respectively). Meanwhile, significant association also existed between SNP rs16861194 and the systolic BP response to potassium supplementation intervention (P=0.026). In addition, SNP rs822394 was significantly associated with basal DBP after adjustment for multiple testing (P=0.033). Our study indicated that the genetic polymorphisms in the adiponectin gene are significantly associated with BP responses to dietary sodium and potassium intake.

  5. Annexin A6 regulates adipocyte lipid storage and adiponectin release.

    PubMed

    Krautbauer, Sabrina; Haberl, Elisabeth M; Eisinger, Kristina; Pohl, Rebekka; Rein-Fischboeck, Lisa; Rentero, Carles; Alvarez-Guaita, Anna; Enrich, Carlos; Grewal, Thomas; Buechler, Christa; Neumeier, Markus

    2017-01-05

    Lipid storage and adipokine secretion are critical features of adipocytes. Annexin A6 (AnxA6) is a lipid-binding protein regulating secretory pathways and its role in adiponectin release was examined. The siRNA-mediated AnxA6 knock-down in 3T3-L1 preadipocytes impaired proliferation, and differentiation of AnxA6-depleted cells to mature adipocytes was associated with higher soluble adiponectin and increased triglyceride storage. The latter was partly attributed to reduced lipolysis. Accordingly, AnxA6 overexpression in 3T3-L1 adipocytes lowered cellular triglycerides and adiponectin secretion. Indeed, serum adiponectin was increased in AnxA6 deficient mice. Expression analysis identified AnxA6 protein to be more abundant in intra-abdominal compared to subcutaneous adipose tissues of mice and men. AnxA6 protein levels increased in white adipose tissues of obese mice and here, levels were highest in subcutaneous fat. AnxA6 protein in adipocytes was upregulated by oxidative stress which might trigger AnxA6 induction in adipose tissues and contribute to impaired fat storage and adiponectin release.

  6. Prediagnostic Plasma Adiponectin and Survival among Patients with Colorectal Cancer.

    PubMed

    Chong, Dawn Q; Mehta, Raaj S; Song, Mingyang; Kedrin, Dmitriy; Meyerhardt, Jeffrey A; Ng, Kimmie; Wu, Kana; Fuchs, Charles S; Giovannucci, Edward L; Ogino, Shuji; Chan, Andrew T

    2015-12-01

    Circulating adiponectin is inversely related to the risk of colorectal cancer. However, its influence on colorectal cancer survival is unclear. We conducted a prospective study to evaluate the association between prediagnostic plasma levels of adiponectin and mortality in patients with colorectal cancer. We identified 621 incident colorectal cancer cases who provided blood specimens prior to diagnosis within the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI). After a median follow-up of 9 years, there were 269 (43%) total deaths, of which 181 (67%) were due to colorectal cancer. Compared with participants in the lowest quartile of adiponectin, those in the highest quartile had multivariate HRs of 1.89 (95% CI, 1.21-2.97; P(trend) = 0.01) for colorectal cancer-specific mortality and 1.66 (95% CI, 1.15-2.39; P(trend) = 0.009) for overall mortality. The apparent increased risk in colorectal cancer-specific mortality was more pronounced in patients with metastatic disease (HR, 3.02: 95% CI, 1.50-6.08). Among patients with colorectal cancer, prediagnostic plasma adiponectin is associated with an increased risk of colorectal cancer-specific and overall mortality and is more apparent in patients with metastatic disease. Adiponectin may be a marker for cancers which develop through specific pathways that may be associated with worsened prognosis. Further studies are needed to validate these findings.

  7. Prediagnostic Plasma Adiponectin and Survival among Patients with Colorectal Cancer

    PubMed Central

    Chong, Dawn Q.; Mehta, Raaj S.; Song, Mingyang; Kedrin, Dmitriy; Meyerhardt, Jeffrey A.; Ng, Kimmie; Wu, Kana; Fuchs, Charles S.; Giovannucci, Edward L.; Ogino, Shuji; Chan, Andrew T.

    2015-01-01

    Circulating adiponectin is inversely related to the risk of colorectal cancer (CRC). However, its influence on CRC survival is unclear. We conducted a prospective study to evaluate the association between prediagnostic plasma levels of adiponectin and mortality in patients with CRC. We identified 621 incident CRC cases who provided blood specimens prior to diagnosis within the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After a median follow-up of 9 years, there were 269 (43%) total deaths, of which 181 (67%) were due to CRC. Compared with participants in the lowest quartile of adiponectin, those in the highest quartile had multivariate HRs of 1.89 (95% CI, 1.21–2.97; Ptrend = 0.01) for CRC-specific mortality and 1.66 (95% CI, 1.15–2.39; Ptrend = 0.009) for overall mortality. The apparent increased risk in CRC-specific mortality was more pronounced in patients with metastatic disease (HR 3.02, 95% CI, 1.50–6.08). Among patients with CRC, prediagnostic plasma adiponectin is associated with an increased risk of CRC-specific and overall mortality, and is more apparent in patients with metastatic disease. Adiponectin may be a marker for cancers which develop through specific pathways that may be associated with worsened prognosis. Further studies are needed to validate these findings. PMID:26382604

  8. Role of leptin and adiponectin in insulin resistance.

    PubMed

    Yadav, Amita; Kataria, Megha A; Saini, Vandana; Yadav, Anil

    2013-02-18

    Adipose tissue is a major source of energy for the human body. It is also a source of major adipocytokines adiponectin and leptin. Insulin resistance is a condition in which insulin action is impaired in adipose tissue and is more strongly linked to intra-abdominal fat than to fat in other depots. The expression of adiponectin decreases with increase in the adiposity. Adiponectin mediates insulin-sensitizing effect through binding to its receptors AdipoR1 and AdipoR2, leading to activation of adenosine monophosphate dependent kinase (AMPK), PPAR-α, and presumably other yet-unknown signalling pathways. Weight loss significantly elevates plasma adiponectin levels. Reduction of adiponectin has been associated with insulin resistance, dyslipidemia, and atherosclerosis in humans. The other major adipokine is leptin. Leptin levels increase in obesity and subcutaneous fat has been a major determinant of circulating leptin levels. The leptin signal is transmitted by the Janus kinase, signal transducer and activator of transcription ((JAK-STAT) pathway. The net action of leptin is to inhibit appetite, stimulate thermogenesis, enhance fatty acid oxidation, decrease glucose, and reduce body weight and fat.

  9. Effect of Drinking on Adiponectin in Healthy Men and Women

    PubMed Central

    Imhof, Armin; Plamper, Ines; Maier, Steffen; Trischler, Gerlinde; Koenig, Wolfgang

    2009-01-01

    OBJECTIVE Moderate alcohol consumption is associated with reduced incidence of type 2 diabetes and cardiovascular mortality and increases adiponectin concentrations, but effects might differ according to sex and beverage consumed. RESEARCH DESIGN AND METHODS A total of 72 healthy individuals (22–56 years) were enrolled in this randomized controlled crossover trial. After washout, two interventions for 3 weeks followed: ethanol (concentration 12.5%), beer (5.6%), or red wine (12.5%) equivalent to 30 g ethanol/day for men and 20 g/day for women or the same de-alcoholized beverages or water. Adiponectin was measured by sandwich enzyme-linked immunosorbent assay. RESULTS Among women, adiponectin significantly increased after consuming red wine (29.8%, P < 0.05) and increased among men after ethanol solution (17.4%, P < 0.05) and consuming beer (16.1%, P < 0.05). De-alcoholized beverages had no substantial effect on adiponectin concentrations. CONCLUSIONS Moderate amounts of ethanol-containing beverages increased adiponectin concentrations, but sex-specific effects might depend on type of beverage consumed. PMID:19244090

  10. Similar associations of total adiponectin and high molecular weight adiponectin with cardio-metabolic risk factors in a population of overweight and obese postmenopausal women: a MONET study.

    PubMed

    Elisha, B; Ziai, S; Karelis, A D; Rakel, A; Coderre, L; Imbeault, P; Rabasa-Lhoret, R

    2010-07-01

    The aim of the study was to examine the association between total adiponectin and high molecular weight (HMW) adiponectin levels with cardio-metabolic risk factors in a population of sedentary, overweight, and obese postmenopausal women. Cross-sectional study was carried out on 55 nondiabetic sedentary overweight and obese postmenopausal women aged between 50 and 70 years. Insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp technique. Body composition and visceral fat were measured using dual X-ray absorptiometry and computed tomography, respectively. Other cardio-metabolic risk factors included: plasma lipids, hsC-reactive protein, energy expenditure (doubly labeled water), peak oxygen consumption, muscle strength (using weight training equipment) as well as total and HMW adiponectin. Correlations of total and HMW adiponectin with various cardio-metabolic risk factors were comparable. In addition, regression analysis results showed similar independent predictors of total and HMW adiponectin. Finally, the receiver operator characteristic (ROC) curves for total and HMW adiponectin to predict insulin sensitivity showed no difference between the areas under curve (AUC) (AUC total adiponectin=0.80 [95% CI: 0.66-0.95] versus AUC HMW adiponectin=0.76 [95% CI: 0.60-0.91], p=0.36). The present study indicates that HMW adiponectin does not seem to provide additional information than total adiponectin in relation to cardio-metabolic risk factors in overweight/obese postmenopausal women.

  11. LDL but not HDL increases adiponectin release of primary human adipocytes.

    PubMed

    Krautbauer, Sabrina; Neumeier, Markus; Eisinger, Kristina; Hader, Yvonne; Dada, Ashraf; Schmitz, Gerd; Aslanidis, Charalampos; Buechler, Christa

    2013-12-01

    Adipocytes in obesity have inappropriately low cholesterol while adiponectin release is reduced. Cholesterol shortage may contribute to low adiponectin and 3T3-L1 cells treated with lovastatin have diminished adiponectin in cell supernatants. LDL and HDL deliver cholesterol to adipocytes. LDL but not HDL increases adiponectin in cell supernatants of primary human adipocytes. The effect of LDL is not blocked by receptor associated protein suggesting that members of the LDL-receptor family are not involved. To evaluate whether these in vitro observations translate into changes in systemic adiponectin, adiponectin was measured in serum of three patients before, immediately after and 3d after LDL-apheresis. Whereas circulating lipoproteins are reduced immediately after apheresis adiponectin is not changed. Therefore, acute lowering of lipoproteins does not affect systemic adiponectin also excluding that plenty of adiponectin is bound to lipoprotein particles. Accordingly, levels of adiponectin in purified lipoproteins are quite low. Familial hypobetalipoproteinemia (FHBL) is a rare disorder associated with low plasma LDL. Serum adiponectin is, however, similar compared to healthy controls. Thus, neither LDL nor HDL directly contributes to circulating adiponectin concentrations.

  12. Circadian expression of adiponectin and its receptors in human adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adiponectin is one of the most clinically relevant cytokines associated with obesity. However, circadian rhythmicity of adiponectin in human adipose tissue (AT) has not been analyzed. To assess whether the mRNA levels of adiponectin and its receptors (ADIPOR1 and ADIPOR2) might show daily circadian ...

  13. A Moderate Low-Carbohydrate Low-Calorie Diet Improves Lipid Profile, Insulin Sensitivity and Adiponectin Expression in Rats

    PubMed Central

    Chen, Jie-Hua; Ouyang, Caiqun; Ding, Qiang; Song, Jia; Cao, Wenhong; Mao, Limei

    2015-01-01

    Calorie restriction (CR) via manipulating dietary carbohydrates has attracted increasing interest in the prevention and treatment of metabolic syndrome. There is little consensus about the extent of carbohydrate restriction to elicit optimal results in controlling metabolic parameters. Our study will identify a better carbohydrate-restricted diet using rat models. Rats were fed with one of the following diets for 12 weeks: Control diet, 80% energy (34% carbohydrate-reduced) and 60% energy (68% carbohydrate-reduced) of the control diet. Changes in metabolic parameters and expressions of adiponectin and peroxisome proliferator activator receptor γ (PPARγ) were identified. Compared to the control diet, 68% carbohydrate-reduced diet led to a decrease in serum triglyceride and increases inlow density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C) and total cholesterol; a 34% carbohydrate-reduced diet resulted in a decrease in triglycerides and an increase in HDL-cholesterol, no changes however, were shown in LDL-cholesterol and total cholesterol; reductions in HOMA-IR were observed in both CR groups. Gene expressions of adiponectin and PPARγ in adipose tissues were found proportionally elevated with an increased degree of energy restriction. Our study for the first time ever identified that a moderate-carbohydrate restricted diet is not only effective in raising gene expressions of adiponectin and PPARγ which potentially lead to better metabolic conditions but is better at improving lipid profiles than a low-carbohydrate diet in rats. PMID:26110252

  14. [Adiponectin receptor-targeted therapy for lifestyle-related diseases].

    PubMed

    Iwabu, Masato; Yamauchi, Toshimasa; Okada-Iwabu, Miki; Kadowaki, Takashi

    2016-03-01

    Given that appropriate control of responses of the body to nutritional status is assumed to modulate the pace of aging, thus prolonging lifespan and maintaining youth in humans, expectations are mounting worldwide for modalities targeting the pathways in metabolic regulation for healthy longevity. Of these, this review focuses attention on adiponectin-targeted therapy and discusses milestones in this approach, which include the discovery of the ability of adiponectin to protect against lifestyle-related diseases, identification of its receptors (AdipoRs), elucidation of AdipoR-mediated signaling pathways that promote healthy longevity and acquisition of small-molecule AdipoR agonist, and explores future prospects on adiponectin-targeted therapy.

  15. Melatonin modulates adiponectin expression on murine colitis with sleep deprivation

    PubMed Central

    Kim, Tae Kyun; Park, Young Sook; Baik, Haing-Woon; Jun, Jin Hyun; Kim, Eun Kyung; Sull, Jae Woong; Sung, Ho Joong; Choi, Jin Woo; Chung, Sook Hee; Gye, Myung Chan; Lim, Ju Yeon; Kim, Jun Bong; Kim, Seong Hwan

    2016-01-01

    AIM To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation. METHODS The following five groups of C57BL/6 mice were used in this study: (1) group I, control; (2) group II, 2% DSS induced colitis for 7 d; (3) group III, 2% DSS induced colitis and melatonin treatment; (4) group IV, 2% DSS induced colitis with sleep deprivation (SD) using specially designed and modified multiple platform water baths; and (5) group V, 2% DSS induced colitis with SD and melatonin treatment. Melatonin (10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti-adiponectin antibody. After sampling by intracardiac punctures, levels of serum cytokines were measured by ELISA. RESULTS Sleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury, but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis, with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly (P < 0.05) recovered the expression of adiponectin. The expression levels of IL-6 and IL-17 were increased in the serum of mice with DSS colitis but decreased after melatonin injection. CONCLUSION This study suggested that melatonin modulated adiponectin expression in colonic tissue and melatonin and adiponectin synergistically potentiated anti-inflammatory effects on colitis with sleep deprivation. PMID:27672276

  16. Development of second generation peptides modulating cellular adiponectin receptor responses

    NASA Astrophysics Data System (ADS)

    Otvos, Laszlo; Knappe, Daniel; Hoffmann, Ralf; Kovalszky, Ilona; Olah, Julia; Hewitson, Tim; Stawikowska, Roma; Stawikowski, Maciej; Cudic, Predrag; Lin, Feng; Wade, John; Surmacz, Eva; Lovas, Sandor

    2014-10-01

    The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC). In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML) cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399). The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400) was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400) at similar concentrations will be an important target validation tool to study adiponectin functions.

  17. Adiponectin and visfatin concentrations in children treated with valproic acid.

    PubMed

    Rauchenzauner, Markus; Haberlandt, Edda; Scholl-Bürgi, Sabine; Ernst, Barbara; Hoppichler, Fritz; Karall, Daniela; Ebenbichler, Christoph F; Rostasy, Kevin; Luef, Gerhard

    2008-02-01

    Chronic antiepileptic therapy with valproic acid (VPA) is associated with increased body weight and insulin resistance in adults and children. Attempts to determine the underlying pathophysiologic mechanisms have failed. Adipocytokines have recently been defined as a link between glucose and fat metabolism. We herein demonstrate that VPA-associated overweight is accompanied by lower adiponectin and higher leptin concentrations in children. The absence of any relationship with visfatin concentration does not suggest a role of this novel insulin-mimetic hormone in VPA-associated metabolic alterations. Therefore, adiponectin and leptin but not visfatin may be considered as potential regulators of glucose and fat metabolism during VPA-therapy.

  18. Adiponectin regulate growth hormone secretion via adiponectin receptor mediated Ca(2+) signalling in rat somatotrophs in vitro.

    PubMed

    Steyn, F J; Boehme, F; Vargas, E; Wang, K; Parkington, H C; Rao, J R; Chen, C

    2009-08-01

    Obesity is associated with reduced levels of growth hormone (GH) and the disruption of pulsatile GH secretion. This results in relative GH deficiency. It is likely that a regulatory relationship between GH secretion and adipose tissue exists as the secretion of GH recovers to normal levels after a reduction in body weight. This report characterise the expression and interaction of adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) and adiponectin, respectively, in regulating the activity of GH secreting cells. Polymerase chain reaction analysis of the GH3 cell line, rat anterior pituitary gland and isolated somatotroph cells from transgenic GFP expressing mice confirmed the expression of both AdipoR1 and AdipoR2 in GH secretory cells. Because GH cells expressed both receptors, it is likely that the measured increase in GH secretion, observed in primary cultured rat pituitary cells after 30 min of incubation with full-length murine adiponectin, was mediated by a direct receptor regulated process. Adiponectin induced an increase in intracellular Ca(2+) through both the influx of extracellular Ca(2+) and the release of intracellular Ca(2+) stores resulting in the secretion of GH. Furthermore, results confirm that this increase in GH secretion depended mainly on an increase in Ca(2+) influx through L-type Ca(2+) channels. It is concluded that adiponectin directly regulates GH secretion from somatotrophs by binding to either adiponectin receptor, and that this is mediated via a similar process observed after the stimulation of GH secretion by GH-releasing hormone.

  19. PLASMA ADIPONECTIN CONCENTRATIONS IN NON PREGNANT, NORMAL PREGNANCY AND OVERWEIGHT PREGNANT WOMEN

    PubMed Central

    Nien, Jyh Kae; Mazaki-Tovi, Shali; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Gotsch, Francesca; Pineles, Beth L.; Gomez, Ricardo; Edwin, Samuel; Mazor, Moshe; Espinoza, Jimmy; Yoon, Bo Hyun; Hassan, Sonia S.

    2008-01-01

    Aims Adiponectin is an adipokine that has anti-diabetic, anti-atherogenic, anti-inflammatory and angiogenic properties. This hormone has been implicated in both the physiological adaptation to normal pregnancy and obstetrical complications. The aims of this study were to determine normal maternal plasma concentrations of adiponectin throughout gestation and to explore the relationships between plasma adiponectin concentration, pregnancy, and maternal overweight. Study design A cross-sectional study was designed to include normal pregnant women (normal weight and overweight; 11–42 weeks of gestation), and non-pregnant women. Plasma adiponectin concentration was determined by immunoassay. Non-parametric statistics were used for analysis. Results (1) Adiponectin was detectable in the plasma of all patients; (2) there was no significant difference in the median adiponectin concentrations between pregnant and non-pregnant women; (3) plasma adiponectin concentrations were negatively correlated with gestational age only among normal weight pregnant women; and (4) overweight patients had significantly lower adiponectin concentrations than normal weight women. Conclusion Consistent with the increased insulin resistance and weight gain that occur in pregnancy, adiponectin concentrations were negatively correlated with gestational age. The results of this study and the nomogram herein presented can serve as the basis to explore the relationship between adiponectin and pregnancy complications and facilitate the clinical use of this important adipokine. Condensation Plasma adiponectin concentrations decrease with advancing gestational age only in nonobese women. PMID:17919116

  20. Inhibition of smooth muscle cell proliferation by adiponectin requires proteolytic conversion to its globular form.

    PubMed

    Fuerst, Melissa; Taylor, Carla G; Wright, Brenda; Tworek, Leslee; Zahradka, Peter

    2012-10-01

    Accelerated atherosclerosis is the primary cardiovascular manifestation of diabetes and correlates inversely with levels of circulating adiponectin, an anti-atherosclerotic adipokine that declines in diabetes. We therefore initiated a study to examine the mechanisms by which adiponectin, a hormone released from adipose tissue, influences the proliferation of vascular smooth muscle cells (SMCs). Addition of adiponectin to quiescent porcine coronary artery SMCs increased both protein and DNA synthesis and concurrently activated ERK1/2 and Akt. By contrast, globular adiponectin, a truncated form of this protein, exhibited anti-mitogenic properties as indicated by the inhibition of protein and DNA synthesis in SMCs stimulated with platelet-derived growth factor (PDGF). Whereas globular adiponectin did not stimulate growth-related signal transduction pathways, it was able to block the PDGF-dependent phosphorylation of eukaryotic elongation factor 2 kinase, a regulator of protein synthesis. Proteolysis of adiponectin with trypsin, which produces globular adiponectin, reversed the growth-stimulating actions of the undigested protein. As the existence of globular adiponectin remains controversial, western blotting was used to establish its presence in rat serum. We found that globular adiponectin was detectable in rat serum, but this result was not obtained with all antibodies. The contrasting properties of adiponectin and its globular form with respect to SMC proliferation suggest that protection against atherosclerosis may therefore be mediated, in part, by the level of globular adiponectin.

  1. Adiponectin self-regulates its expression and multimerization in adipose tissue: an autocrine/paracrine mechanism?

    PubMed

    Lin, Huan; Li, Zhen

    2012-01-01

    Adiponectin, a 30-kDa peptide hormone discovered in the mid 1990s, is secreted abundantly and exclusively by adipose tissue. Adiponectin exists in three major forms: a low molecular weight (LMW) trimer, a medium molecular weight (MMW) hexamer, and a high molecular weight (HMW) 18-36 oligomer. The HMW oligomer has the most potent insulin-sensitizing activity therefore impaired adiponectin multimerization may lead to impaired glycemic control. Decreased ratio of HMW/total adiponectin has been observed in patients with obesity, type-2 diabetes mellitus, cardiovascular diseases and insulin resistance-related metabolic syndrome. Previous studies have indicated that berberine or aminoimidazole carboxamide ribonucleotide (AICAR)-induced activation of AMP-activated protein kinase (AMPK) suppresses the expression of adiponectin but promotes adiponectin multimerization in adipocytes. Since adiponectin activates AMPK through adiponectin receptors (AdipoRs) in the membranes of adipocytes, we speculate that adiponectin self-regulates its expression and multimerization in adipose tissue. The hypothesis suggests a potential drug target for treating insulin resistance and provides new interpretation of several clinical observations. In addition, we propose a rapid method for one-step detection of the distribution of adiponectin oligomers in approximately 30 min, based on the open sandwich immunoassay and fluorescence resonance energy transfer technology. With the development of this new method, the ratio of HMW/total adiponectin may be applied in clinical diagnosis as a novel biomarker for insulin resistance and metabolic disorders.

  2. Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding

    PubMed Central

    Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

    2016-01-01

    Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding. PMID:27503800

  3. Influence of androgens on circulating adiponectin in male and female rodents.

    PubMed

    Yarrow, Joshua F; Beggs, Luke A; Conover, Christine F; McCoy, Sean C; Beck, Darren T; Borst, Stephen E

    2012-01-01

    Several endocrine factors, including sex-steroid hormones are known to influence adiponectin secretion. Our purpose was to evaluate the influence of testosterone and of the synthetic non-aromatizable/non-5α reducible androgen 17β-hydroxyestra-4,9,11-trien-3-one (trenbolone) on circulating adiponectin and adiponectin protein expression within visceral fat. Young male and female F344 rats underwent sham surgery (SHAM), gonadectomy (GX), or GX plus supraphysiologic testosterone-enanthate (TE) administration. Total circulating adiponectin was 39% higher in intact SHAM females than SHAM males (p<0.05). GX increased total adiponectin by 29-34% in both sexes (p<0.05), while TE reduced adiponectin to concentrations that were 46-53% below respective SHAMs (p≤0.001) and ablated the difference in adiponectin between sexes. No differences in high molecular weight (HMW) adiponectin were observed between sexes or treatments. Adiponectin concentrations were highly and negatively associated with serum testosterone (males: r = -0.746 and females: r = -0.742, p≤0.001); however, no association was present between adiponectin and estradiol. In separate experiments, trenbolone-enanthate (TREN) prevented the GX-induced increase in serum adiponectin (p≤0.001) in young animals, with Low-dose TREN restoring adiponectin to the level of SHAMs and higher doses of TREN reducing adiponectin to below SHAM concentrations (p≤0.001). Similarly, TREN reduced adiponectin protein expression within visceral fat (p<0.05). In adult GX males, Low-dose TREN also reduced total adiponectin and visceral fat mass to a similar magnitude as TE, while increasing serum HMW adiponectin above SHAM and GX animals (p<0.05). Serum adiponectin was positively associated with visceral fat mass in young (r = 0.596, p≤0.001) and adult animals (r = 0.657, p≤0.001). Our results indicate that androgens reduce circulating total adiponectin concentrations in a dose-dependent manner, while maintaining HMW

  4. Differential Role of Leptin and Adiponectin in Cardiovascular System

    PubMed Central

    Ghantous, C. M.; Azrak, Z.; Hanache, S.; Abou-Kheir, W.; Zeidan, A.

    2015-01-01

    Leptin and adiponectin are differentially expressed adipokines in obesity and cardiovascular diseases. Leptin levels are directly associated with adipose tissue mass, while adiponectin levels are downregulated in obesity. Although significantly produced by adipocytes, leptin is also produced by vascular smooth muscle cells and cardiomyocytes. Plasma leptin concentrations are elevated in cases of cardiovascular diseases, such as hypertension, congestive heart failure, and myocardial infarction. As for the event of left ventricular hypertrophy, researchers have been stirring controversy about the role of leptin in this form of cardiac remodeling. In this review, we discuss how leptin has been shown to play an antihypertrophic role in the development of left ventricular hypertrophy through in vitro experiments, population-based cross-sectional studies, and longitudinal cohort studies. Conversely, we also examine how leptin may actually promote left ventricular hypertrophy using in vitro analysis and human-based univariate and multiple linear stepwise regression analysis. On the other hand, as opposed to leptin's generally detrimental effects on the cardiovascular system, adiponectin is a cardioprotective hormone that reduces left ventricular and vascular hypertrophy, oxidative stress, and inflammation. In this review, we also highlight adiponectin signaling and its protective actions on the cardiovascular system. PMID:26064110

  5. The ratio of high-molecular weight adiponectin and total adiponectin differs in preterm and term infants.

    PubMed

    Yoshida, Tomohide; Nagasaki, Hiraku; Asato, Yoshihide; Ohta, Takao

    2009-05-01

    Adiponectin consists of three subspecies (high-, middle- and low-molecular weight adiponectin). Among these, high-molecular weight adiponectin (H-adn) is suggested to be an active form of this protein. To assess the relationship between H-adn and postnatal growth in preterm infants (PIs), serum H-adn and total adiponectin (T-adn) were measured in 46 PIs at birth and at corrected term, and 26 term infants (TI) at birth. T-adn and H-adn concentrations, and the ratio of H-adn to T-adn (H/T-adn) were significantly greater in TI and PI at corrected term than in PI at birth (p < 0.001). T-adn and H-adn concentrations in PI at corrected term were similar to those in TI, but H/T-adn in PI at corrected term was less than that in TI (p < 0.02). Stepwise multiple regression analysis revealed that the factors contributing to H/T-adn and serum concentrations of T- and H-adn in PI at corrected term were different from those in TI. These data suggest that quality of early postnatal growth in PIs is different from that in normally developed TI. Postnatal growth accompanying adipose tissue similar to TI may be important for PI to prevent future development of cardiovascular disease.

  6. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway

    SciTech Connect

    Luo Xianghang; Guo Lijuan; Yuan Lingqing; Xie Hui; Zhou Houde; Wu Xianping; Liao Eryuan . E-mail: eyliao1207@21cn.com

    2005-09-10

    Adipocytes can highly and specifically express adiponectin, and the adiponectin receptor (AdipoR) has been detected in bone-forming cells. The present study was undertaken to investigate the action of adiponectin on osteoblast proliferation and differentiation. AdipoR1 protein was detected in human osteoblasts. Adiponectin promoted osteoblast proliferation and resulted in a dose- and time-dependent increase in alkaline phosphatase (ALP) activity, osteocalcin and type I collagen production, and an increase in mineralized matrix. Suppression of AdipoR1 with small-interfering RNA (siRNA) abolished the adiponectin-induced cell proliferation and ALP expression. Adiponectin induces activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal Kinase (JNK), but not ERK1/2 in osteoblasts, and these effects were blocked by suppression of AdipoR1 with siRNA. Furthermore, pretreatment of osteoblasts with the JNK inhibitor SP600125 abolished the adiponectin-induced cell proliferation. p38 inhibitor SB203580 blocked the adiponectin-induced ALP activity. These data indicate that adiponectin induces human osteoblast proliferation and differentiation, and the proliferation response is mediated by the AdipoR/JNK pathway, while the differentiation response is mediated via the AdipoR/p38 pathway. These findings suggest that osteoblasts are the direct targets of adiponectin.

  7. Adiponectin does not bind to gelatin: a new and easy way to purify high-molecular-weight adiponectin from human plasma.

    PubMed

    Nakano, Yasuko; Shoji, Ayako; Arakawa, Atsushi; Iizuka, Yumiko; Kikuchi, Yuriko; Kobayashi, Maya; Tobe, Takashi

    2010-01-01

    Human plasma contains three forms of adiponectin, a trimer, a hexamer, and a high-molecular-weight (HMW) multimer. We previously reported HMW adiponectin was a gelatin-binding protein of 28 kDa (GBP28), it having been purified due to its affinity to gelatin-Cellulofine (Nakano, Y., et al. Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J. Biochem. 1996. 120: 803-12). Although HMW adiponectin binds to gelatin-Cellulofine, it cannot bind to gelatin-Sepharose. Gelatin-Cellulofine was made of formyl-Cellulofine and gelatin, and we found that HMW adiponectin binds to reduced formyl-Cellulofine with similar affinity as to gelatin-Cellulofine. Through only two steps using reduced formyl-Cellulofine and DEAE-Sepharose, HMW adiponectin can be effectively purified from human plasma.

  8. Uncovering Adiponectin Replenishing Property of Sujiaonori Algal Biomaterial in Humans.

    PubMed

    Ngatu, Nlandu Roger; Ikeda, Mitsunori; Watanabe, Hiroyuki; Tanaka, Mamoru; Inoue, Masataka; Kanbara, Sakiko; Nojima, Sayumi

    2017-02-08

    The replenishment of adiponectin-an adipocyte-derived hormone with salutary health effects-has recently been proposed as a new approach to treat hypertension, also ameliorate cardiovascular and metabolic risks. We conducted a prospective placebo-controlled, non-randomized and investigator-blinded dietary intervention study to evaluate the health effects of dietary intake of Sujiaonori (Ulva/Enteromorpha prolifera Müller) algal biomaterial (SBM), especially on adiponectin production, blood pressure (BP), and body mass index (BMI) in human subjects. Participants (N = 32) were divided into two equally sized groups (n = 16 for each group): SBM group (subjects supplemented with 3 g SBM powder twice a day during meal) and the control group (subjects who took 3 g of a supplement made of 70% corn starch powder and 30% spinach twice a day) for four weeks. Two health survey questionnaires (dietary and current health questionnaires) were completed anonymously, saliva sampling was done for adiponectin measurement by ELISA, and blood pressure (BP) and anthropometric parameters were measured at baseline and four weeks later. Student paired t-test was performed to compare baseline and post-intervention data on outcome variables between the two study groups. Results showed a 2.24-fold increase in adiponectin level in SBM group (2.81 and 6.26 ng/mL at baseline and at the end of study, respectively) (p < 0.01); whereas no significant change was observed in controls (3.58 and 3.51 ng/mL, respectively) (p > 0.05). In SBM subjects, an improvement of BP profile was noted with a significant decrease in systolic BP (p < 0.01). A positive correlation was found between SBM supplementation and adiponectin level, whereas an inverse correlation was noted between SBM supplementation and blood pressure, and also BMI. These findings suggest that SBM-increased adiponectin level and improved BP in a sample of Japanese young adults, and has the potential to improve blood pressure in humans.

  9. Disulfide-Dependent Self-Assembly of Adiponectin Octadecamers from Trimers and Presence of Stable Octadecameric Adiponectin Lacking Disulfide Bonds In Vitro†

    PubMed Central

    Briggs, David B.; Jones, Christopher M.; Mashalidis, Ellene H.; Nuñez, Martha; Hausrath, Andrew C.; Wysocki, Vicki H.; Tsao, Tsu-Shuen

    2009-01-01

    Adiponectin is a circulating insulin-sensitizing hormone that homo-oligomerizes into trimers, hexamers, and higher molecular weight (HMW) species. Low levels of circulating HMW adiponectin appear to increase the risk for insulin resistance. Currently, assembly of adiponectin oligomers, and consequently mechanisms responsible for decreased HMW adiponectin in insulin resistance, are not well understood. In the work reported here, we analyzed the re-assembly of the most abundant HMW adiponectin species, the octadecamer, following its collapse to smaller oligomers in vitro. Purified bovine serum adiponectin octadecamer was treated with reducing agents at pH 5 to obtain trimers. These reduced trimers partially and spontaneously reassembled into octadecamers upon oxidative formation of disulfide bonds. Disulfide bonds appear to occupy a greater role in the process of oligomerization than in the structural stabilization of mature octadecamer. Stable octadecamers lacking virtually all disulfide bonds could be observed in abundance using native gel electrophoresis, dynamic light scattering, and collision-induced dissociation nano-electrospray ionization mass spectrometry. These findings indicate that while disulfide bonds help to maintain the mature octadecameric adiponectin structure, their more important function is to stabilize intermediates during the assembly of octadecamer. Adiponectin oligomerization must proceed through intermediates that are at least partially reduced. Accordingly, fully oxidized adiponectin hexamers failed to reassemble into octadecamers at a rate comparable to that of reduced trimers. As the findings from the present study are based on in vitro experiments, their in vivo relevance remains unclear. Nevertheless, they describe a redox environment-dependent model of adiponectin oligomerization that can be tested using cell-based approaches. PMID:19943704

  10. The emerging roles of adiponectin in female reproductive system-associated disorders and pregnancy.

    PubMed

    Angelidis, George; Dafopoulos, Konstantinos; Messini, Christina I; Valotassiou, Varvara; Tsikouras, Panagiotis; Vrachnis, Nikolaos; Psimadas, Dimitrios; Georgoulias, Panagiotis; Messinis, Ioannis E

    2013-08-01

    Adiponectin, the most abundant adipose-released cytokine, has an important role in metabolism, primarily through reducing insulin resistance. Reproductive functions are known to be influenced by energy balance and adiponectin may be involved in the underlying mechanisms connecting reproduction and metabolism. Interestingly, adiponectin has been shown to exert actions in the female reproductive system, including the hypothalamic-pituitary-ovarian axis and the endometrium. The peripheral effects of this adipocytokine are mediated mainly via 2 receptors, AdipoR1 and AdipoR2. The expression of these receptors has been reported in the brain, ovaries, endometrium, and the placenta. Thus, adiponectin may influence fertility and pregnancy. Furthermore, adiponectin concentrations and effects have been assessed in some pregnancy-associated disorders and gynecological conditions. The findings may lead to the use of adiponectin or its receptors as therapeutic targets in novel treatment strategies of these disorders.

  11. Inside out: Bone marrow adipose tissue as a source of circulating adiponectin

    PubMed Central

    Scheller, Erica L.; Burr, Aaron A.; MacDougald, Ormond A.; Cawthorn, William P.

    2016-01-01

    ABSTRACT The adipocyte-derived hormone adiponectin mediates beneficial cardiometabolic effects, and hypoadiponectinemia is a biomarker for increased metabolic and cardiovascular risk. Indeed, circulating adiponectin decreases in obesity and insulin-resistance, likely because of impaired production from white adipose tissue (WAT). Conversely, lean states such as caloric restriction (CR) are characterized by hyperadiponectinemia, even without increased adiponectin production from WAT. The reasons underlying this paradox have remained elusive, but our recent research suggests that CR-associated hyperadiponectinemia derives from an unexpected source: bone marrow adipose tissue (MAT). Herein, we elaborate on this surprising discovery, including further discussion of potential mechanisms influencing adiponectin production from MAT; additional evidence both for and against our conclusions; and observations suggesting that the relationship between MAT and adiponectin might extend beyond CR. While many questions remain, the burgeoning study of MAT promises to reveal further key insights into MAT biology, both as a source of adiponectin and beyond. PMID:27617171

  12. Effect of monomeric adiponectin on cardiac function and perfusion in anesthetized pig.

    PubMed

    Grossini, Elena; Prodam, Flavia; Walker, Gillian Elisabeth; Sigaudo, Lorenzo; Farruggio, Serena; Bellofatto, Kevin; Marotta, Patrizia; Molinari, Claudio; Mary, David; Bona, Gianni; Vacca, Giovanni

    2014-07-01

    Adiponectin, the most abundant adipokine released by adipose tissue, appears to play an important role in the regulation of vascular endothelial and cardiac function. To date, however, the physiological effects of human monomeric adiponectin on the coronary vasculature and myocardial systo-diastolic function, as well as on parasympathetic/sympathetic involvement and nitric oxide (NO) release, have not yet been investigated. Thus, we planned to determine the primary in vivo effects of human monomeric adiponectin on coronary blood flow and cardiac contractility/relaxation and the related role of autonomic nervous system, adiponectin receptors, and NO. In 30 anesthetized pigs, human monomeric adiponectin was infused into the left anterior descending coronary artery at constant heart rate and arterial blood pressure, and the effects on coronary blood flow, left ventricular systo-diastolic function, myocardial oxygen metabolism, and NO release were examined. The mechanisms of the observed hemodynamic responses were also analyzed by repeating the highest dose of human monomeric adiponectin infusion after autonomic nervous system and NO blockade, and after specific adiponectin 1 receptor antagonist administration. Intracoronary human monomeric adiponectin caused dose-related increases of coronary blood flow and cardiac function. Those effects were accompanied by increased coronary NO release and coronary adiponectin levels. Moreover, the vascular effects of the peptide were prevented by blockade of β2-adrenoceptors and NO synthase, whereas all effects of human monomeric adiponectin were prevented by adiponectin 1 receptor inhibitor. In conclusion, human monomeric adiponectin primarily increased coronary blood flow and cardiac systo-diastolic function through the involvement of specific receptors, β2-adrenoceptors, and NO release.

  13. Unique profile of chicken adiponectin, a predominantly heavy molecular weight multimer, and relationship to visceral adiposity.

    PubMed

    Hendricks, Gilbert L; Hadley, Jill A; Krzysik-Walker, Susan M; Prabhu, K Sandeep; Vasilatos-Younken, Regina; Ramachandran, Ramesh

    2009-07-01

    Adiponectin, a 30-kDa adipokine hormone, circulates as heavy, medium, and light molecular weight isoforms in mammals. Plasma heavy molecular weight (HMW) adiponectin isoform levels are inversely correlated with the incidence of type 2 diabetes in humans. The objectives of the present study were to characterize adiponectin protein and quantify plasma adiponectin levels in chickens, which are naturally hyperglycemic relative to mammals. Using gel filtration column chromatography and Western blot analysis under nonreducing and non-heat-denaturing native conditions, adiponectin in chicken plasma, and adipose tissue is predominantly a multimeric HMW isoform that is larger than 669 kDa mass. Under reducing conditions and heating to 70-100 C, however, a majority of the multimeric adiponectin in chicken plasma and adipose tissue was reduced to oligomeric and/or monomeric forms. Immunoprecipitation and elution under neutral pH preserved the HMW adiponectin multimer, whereas brief exposure to acidic pH led to dissociation of HMW multimer into multiple oligomers. Mass spectrometric analysis of chicken adiponectin revealed the presence of hydroxyproline and differential glycosylation of hydroxylysine residues in the collagenous domain. An enzyme immunoassay was developed and validated for quantifying plasma adiponectin in chickens. Plasma adiponectin levels were found to be significantly lower in 8- compared with 4-wk-old male chickens and inversely related to abdominal fat pad mass. Collectively, our results provide novel evidence that adiponectin in chicken plasma and tissues is predominantly a HMW multimer, suggesting the presence of unique multimerization and stabilization mechanisms in the chicken that favors preponderance of HMW adiponectin over other oligomers.

  14. Physiological, Pharmacological, and Nutritional Regulation of Circulating Adiponectin Concentrations in Humans

    PubMed Central

    Swarbrick, Michael M.

    2008-01-01

    Abstract Adiponectin is an adipocyte hormone that links visceral adiposity with insulin resistance and atherosclerosis. It is unique among adipocyte-derived hormones in that its circulating concentrations are inversely proportional to adiposity, and low adiponectin concentrations predict the development of type 2 diabetes and cardiovascular disease. Consequently, in the decade since its discovery, adiponectin has generated immense interest as a potential therapeutic target for the metabolic syndrome and diabetes. This review summarizes current research regarding the regulation of circulating adiponectin concentrations by physiological, pharmacological, and nutritional factors, with an emphasis on human studies. In humans, plasma adiponectin concentrations are influenced by age and gender, and are inversely proportional to visceral adiposity. In vitro studies suggest that adiponectin production may be determined primarily by adipocyte size and insulin sensitivity, with larger, insulin-resistant adipocytes producing less adiponectin. While adiponectin concentrations are unchanged after meal ingestion, they are increased by significant weight loss, such as after bariatric surgery. In addition, adiponectin production is inhibited by a number of hormones, including testosterone, prolactin, glucocorticoids and growth hormone, and by inflammation and oxidative stress in adipose tissue. Smoking decreases, while moderate alcohol consumption increases, circulating adiponectin concentrations. Dietary fatty acid composition in rodents influences adiponectin production via ligand-activated nuclear receptors (PPARs); however, current evidence in humans is equivocal. In addition to PPAR agonists (such as thiazolidinediones and fibrates), a number of pharmacological agents (angiotensin receptor type 1 blockers, ACE inhibitors, and cannabinoid receptor antagonists) used in treatment of the metabolic syndrome also increase adiponectin concentrations in humans. PMID:18510434

  15. The Effects of Aerobic Exercise on Plasma Adiponectin Level and Adiponectin-related Protein Expression in Myocardial Tissue of ApoE(-/-) Mice.

    PubMed

    Zhu, Xiao-Juan; Chen, Li-Hui; Li, Jiang-Hua

    2015-12-01

    Numerous reports have confirmed the effect of ApoE knockout in the induction of cardiovascular diseases and the protective effect of adiponectin against the progression of cardiovascular diseases. The aim of this study was to reveal the roles of adiponectin signaling in the progression of cardiovascular diseases induced by ApoE knockout and to analyze the healthy effects of aerobic exercise on ApoE knockout mice (ApoE(-/-) mice) through observing the changes of adiponectin signaling caused by ApoE knockout and aerobic exercise. A twelve-week aerobic exercise program was carried out on the male ApoE(-/-) mice and the C57BL / 6J mice (C57 mice) of the same strain. Results show that the body weights, blood lipid level, plasma adiponectin level and adiponectin-related proteins in myocardial tissue were all significantly changed by ApoE knockout. A twelve-week aerobic exercise program exerted only minimal effects on the body weights, blood lipid levels, and plasma adiponectin levels of ApoE(-/-) mice, but increased the expressions of four adiponectin-related proteins, AdipoR1, PPARα, AMPK and P-AMPK, in the myocardial tissue of the ApoE(-/-) mice. In summary, adiponectin signaling may play an import role in the progression of cardiovascular diseases induced by ApoE knockout, and the beneficial health effects of aerobic exercise on ApoE(-/-) mice may be mainly from the increased adiponectin-related protein expression in myocardial tissue. Key pointsA twelve-week aerobic exercise program exerted only limited effects on the body weights and the plasma adiponectin levels of both the normal mice and the ApoE(-/-) mice but did effectively regulate the blood lipid levels of the normal mice (but not the ApoE(-/-) mice).After 12 weeks of aerobic exercise, expression of the adiponectin-related proteins in the myocardial tissue of the ApoE(-/-) and normal mice was increased, but the increased amplitudes of these proteins in the ApoE(-/-) mice were much larger in the Apo

  16. Adiponectin modulates excitability of rat paraventricular nucleus neurons by differential modulation of potassium currents.

    PubMed

    Hoyda, Ted D; Ferguson, Alastair V

    2010-07-01

    The adipocyte-derived hormone adiponectin acts at two seven-transmembrane domain receptors, adiponectin receptor 1 and adiponectin receptor 2, present in the paraventricular nucleus of the hypothalamus to regulate neuronal excitability and endocrine function. Adiponectin depolarizes rat parvocellular preautonomic neurons that secrete either thyrotropin releasing hormone or oxytocin and parvocellular neuroendocrine corticotropin releasing hormone neurons, leading to an increase in plasma adrenocorticotropin hormone concentrations while also hyperpolarizing a subgroup of neurons. In the present study, we investigate the ionic mechanisms responsible for these changes in excitability in parvocellular paraventricular nucleus neurons. Patch clamp recordings of currents elicited from slow voltage ramps and voltage steps indicate that adiponectin inhibits noninactivating delayed rectifier potassium current (I(K)) in a majority of neurons. This inhibition produced a broadening of the action potential in cells that depolarized in the presence of adiponectin. The depolarizing effects of adiponectin were abolished in cells pretreated with tetraethyl ammonium (0/15 cells depolarize). Slow voltage ramps performed during adiponectin-induced hyperpolarization indicate the activation of voltage-independent potassium current. These hyperpolarizing responses were abolished in the presence of glibenclamide [an ATP-sensitive potassium (K(ATP)) channel blocker] (0/12 cells hyperpolarize). The results presented in this study suggest that adiponectin controls neuronal excitability through the modulation of different potassium conductances, effects which contribute to changes in excitability and action potential profiles responsible for peptidergic release into the circulation.

  17. Adiponectin deficiency promotes tumor growth in mice by reducing macrophage infiltration.

    PubMed

    Sun, Yutong; Lodish, Harvey F

    2010-08-05

    Adiponectin is an adipocyte-derived plasma protein that has been implicated in regulating angiogenesis, but the role of adiponectin in regulating this process is still controversial. In this study, in order to determine whether adiponectin affects tumor growth and tumor induced vascularization, we implanted B16F10 melanoma and Lewis Lung Carcinoma cells subcutaneously into adiponectin knockout and wild-type control mice, and found that adiponectin deficiency markedly promoted the growth of both tumors. Immunohistochemical analyses indicated that adiponectin deficiency reduced macrophage recruitment to the tumor, but did not affect cancer cell mitosis, apoptosis, or tumor-associated angiogenesis. In addition, treatment with recombinant adiponectin did not affect the proliferation of cultured B16F10 tumor cells. Importantly, the restoration of microphage infiltration at an early stage of tumorigenesis by means of co-injection of B16F10 cells and macrophages reversed the increased tumor growth in adiponectin knockout mice. Thus, we conclude that the enhanced tumor growth observed in adiponectin deficient mice is likely due to the reduction of macrophage infiltration rather than enhanced angiogenesis.

  18. Uncovering Adiponectin Replenishing Property of Sujiaonori Algal Biomaterial in Humans

    PubMed Central

    Ngatu, Nlandu Roger; Ikeda, Mitsunori; Watanabe, Hiroyuki; Tanaka, Mamoru; Inoue, Masataka; Kanbara, Sakiko; Nojima, Sayumi

    2017-01-01

    The replenishment of adiponectin—an adipocyte-derived hormone with salutary health effects—has recently been proposed as a new approach to treat hypertension, also ameliorate cardiovascular and metabolic risks. We conducted a prospective placebo-controlled, non-randomized and investigator-blinded dietary intervention study to evaluate the health effects of dietary intake of Sujiaonori (Ulva/Enteromorpha prolifera Müller) algal biomaterial (SBM), especially on adiponectin production, blood pressure (BP), and body mass index (BMI) in human subjects. Participants (N = 32) were divided into two equally sized groups (n = 16 for each group): SBM group (subjects supplemented with 3 g SBM powder twice a day during meal) and the control group (subjects who took 3 g of a supplement made of 70% corn starch powder and 30% spinach twice a day) for four weeks. Two health survey questionnaires (dietary and current health questionnaires) were completed anonymously, saliva sampling was done for adiponectin measurement by ELISA, and blood pressure (BP) and anthropometric parameters were measured at baseline and four weeks later. Student paired t-test was performed to compare baseline and post-intervention data on outcome variables between the two study groups. Results showed a 2.24-fold increase in adiponectin level in SBM group (2.81 and 6.26 ng/mL at baseline and at the end of study, respectively) (p < 0.01); whereas no significant change was observed in controls (3.58 and 3.51 ng/mL, respectively) (p > 0.05). In SBM subjects, an improvement of BP profile was noted with a significant decrease in systolic BP (p < 0.01). A positive correlation was found between SBM supplementation and adiponectin level, whereas an inverse correlation was noted between SBM supplementation and blood pressure, and also BMI. These findings suggest that SBM-increased adiponectin level and improved BP in a sample of Japanese young adults, and has the potential to improve blood pressure in humans

  19. Cranberries (Oxycoccus quadripetalus) inhibit lipid metabolism and modulate leptin and adiponectin secretion in 3T3-L1 adipocytes.

    PubMed

    Kowalska, Katarzyna; Olejnik, Anna; Rychlik, Joanna; Grajek, Włodzimierz

    2015-10-15

    It has previously been shown that lyophilized cranberries (LCB) decreased lipid accumulation in 3T3-L1 cells and inhibited preadipocyte differentiation by down-regulation of the expression of key transcription factors (PPARγ, C/EBPα, SREBP1) of the adipogenesis pathway. To elucidate the molecular basis of anti-lipogenic activity of LCB, the expression of several genes involved in lipid metabolism, such as adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), hormone sensitive lipase (HSL) and perilipin 1 (PLIN1), was examined in the present study. Additionally, the effects of LCB on adiponectin and leptin expression and protein secretion were also investigated. LCB reduced lipid accumulation during preadipocyte differentiation by down-regulation of the mRNA level of aP2, FAS, LPL, HSL and PLIN1. Moreover, LCB decreased leptin gene expression and increased adiponectin gene expression and protein secretion in a dose-dependent manner. Therefore cranberries could be considered as bioactive factors, which are effective in the inhibition of adipose tissue mass production.

  20. Adiponectin increases glucose-induced insulin secretion through the activation of lipid oxidation.

    PubMed

    Patané, G; Caporarello, N; Marchetti, P; Parrino, C; Sudano, D; Marselli, L; Vigneri, R; Frittitta, L

    2013-12-01

    The expression of adiponectin receptors has been demonstrated in human and rat pancreatic beta cells, where globular (g) adiponectin rescues rat beta cells from cytokine and fatty acid-induced apoptosis. The aim of our study was to evaluate whether adiponectin has a direct effect on insulin secretion and the metabolic pathways involved. Purified human pancreatic islets and rat beta cells (INS-1E) were exposed (1 h) to g-adiponectin, and glucose-induced insulin secretion was measured. A significant increase in glucose-induced insulin secretion was observed in the presence of g-adiponectin (1 nmol/l) with respect to control cells in both human pancreatic islets (n = 5, p < 0.05) and INS-1E cells (n = 5, p < 0.001). The effect of globular adiponectin on insulin secretion was independent of AMP-dependent protein kinase (AMPK) activation or glucose oxidation. In contrast, g-adiponectin significantly increased oleate oxidation (n = 5, p < 0.05), and the effect of g-adiponectin (p < 0.001) on insulin secretion by INS-1E was significantly reduced in the presence of etomoxir (1 μmol/l), an inhibitor of fatty acid beta oxidation. g-Adiponectin potentiates glucose-induced insulin secretion in both human pancreatic islets and rat beta cells via an AMPK independent pathway. Increased fatty acid oxidation rather than augmented glucose oxidation is the mechanism responsible. Overall, our data indicate that, in addition to its anti-apoptotic action, g-adiponectin has another direct effect on beta cells by potentiating insulin secretion. Adiponectin, therefore, in addition to its well-known effect on insulin sensitivity, has important effects at the pancreatic level.

  1. Protective role of adiponectin in a rat model of intestinal ischemia reperfusion injury

    PubMed Central

    Liu, Xu-Hui; Yang, Yue-Wu; Dai, Hai-Tao; Cai, Song-Wang; Chen, Rui-Han; Ye, Zhi-Qiang

    2015-01-01

    AIM: To determine the potential protective role of adiponectin in intestinal ischemia reperfusion (I/R) injury. METHODS: A rat model of intestinal I/R injury was established. The serum level of adiponectin in rats with intestinal I/R injury was determined by enzyme-linked immunosorbent assay (ELISA). The serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also measured by ELISA. Apoptosis of intestinal cells was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The production of malondialdehyde (MDA) and superoxide dismutase (SOD) and villous injury scores were also measured. RESULTS: Adiponectin was downregulated in the serum of rats with intestinal I/R injury compared with sham rats. No significant changes in the expression of adiponectin receptor 1 and adiponectin receptor 2 were found between sham and I/R rats. Pre-treatment with recombinant adiponectin attenuated intestinal I/R injury. The production of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, in rats with intestinal I/R injury was reduced by adiponectin pre-treatment. The production of MDA was inhibited, and the release of SOD was restored by adiponectin pre-treatment in rats with intestinal I/R injury. Adiponectin pre-treatment also inhibited cell apoptosis in these rats. Treatment with the AMP-activated protein kinase (AMPK) signaling pathway inhibitor, compound C, or the heme oxygenase 1 (HO-1) inhibitor, Snpp, attenuated the protective effects of adiponectin against intestinal I/R injury. CONCLUSION: Adiponectin exhibits protective effects against intestinal I/R injury, which may involve the AMPK/HO-1 pathway. PMID:26715807

  2. Construction of adiponectin-encoding plasmid DNA and overexpression in mice in vivo.

    PubMed

    Huang, Yan-Na; Qi, Jian-Hua; Xiang, Lan; Wang, Yi-Zhen

    2012-07-10

    The effects of elevated adiponectin (ADN) plasma levels on food intake, body weight, and lipid deposition of wild-type mice through ADN gene transfer using hydrodynamic based-gene delivery (HD) were investigated. The administration of pTarget/ADN significantly increased the blood ADN levels on days 1, 3, and 7 as well as food intake and body weight. Reverse transcription polymerase chain reaction (RT-PCR) was used to investigate the key-function genes involved in lipid deposition on epididymal fat, gastrocnemius, and extensor digitorum longus on days 1 and 7. The amounts of adipose triglyceride lipase, hormone-sensitive lipase, and lipoprotein lipase mRNA in the three samples significantly increased. We determined sirtuin 1 (SIRT1), forkhead box O3 (FOXO3a), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) gene expression and protein level in these samples. The amounts of SIRT1, FOXO3a, and PGC-1α mRNA in epididymal fat, gastrocnemius, and extensor digitorum longus remarkably increased. However, a significant increase in SIRT1 and PGC-1α protein levels was only observed in extensor digitorum longus. These results suggest that high doses of ADN can increase food intake and body weight. Elevated ADN levels may also affect fat deposition on the adipose tissue and skeletal muscles of wild-type mice via SIRT1, FOXO3a, and its downstream targets, including PGC-1α.

  3. Adiponectin oligomers and ectopic fat in liver and skeletal muscle in humans.

    PubMed

    Kantartzis, Konstantinos; Staiger, Harald; Machann, Jürgen; Schick, Fritz; Claussen, Claus D; Machicao, Fausto; Fritsche, Andreas; Häring, Hans-Ulrich; Stefan, Norbert

    2009-02-01

    We aimed at determining which circulating forms of the adipokine adiponectin that increases lipid oxidation in liver and skeletal muscle are related to ectopic fat in these depots in humans. Plasma total-, high-molecular weight (HMW)-, middle-molecular weight (MMW)-, and low-molecular weight (LMW) adiponectin were quantified by an enzyme-linked immunosorbent assay. Their relationships with liver- and intramyocellular fat, measured using (1)H magnetic resonance spectroscopy, were investigated in 54 whites without type 2 diabetes. Liver fat, adjusted for gender, age, and total body fat, was associated only with HMW adiponectin (r = -0.35, P = 0.012), but not with total-, MMW-, or LMW adiponectin. In addition, subjects with fatty liver (liver fat > or =5.56%, n = 15) had significantly lower HMW- (P = 0.04), but not total-, MMW-, or LMW adiponectin levels, compared to controls (n = 39). Similarly, intramyocellular fat correlated only with HMW (r = -0.32, P = 0.039), but not with the other circulating forms of adiponectin. These data indicate that, among circulating forms of adiponectin, HMW is strongly related to ectopic fat, thus possibly representing the form of adiponectin regulating lipid oxidation in liver and skeletal muscle.

  4. Adiponectin Induces Oncostatin M Expression in Osteoblasts through the PI3K/Akt Signaling Pathway

    PubMed Central

    Su, Chen-Ming; Lee, Wei-Lin; Hsu, Chin-Jung; Lu, Ting-Ting; Wang, Li-Hong; Xu, Guo-Hong; Tang, Chih-Hsin

    2015-01-01

    Rheumatoid arthritis (RA), a common autoimmune disorder, is associated with a chronic inflammatory response and unbalanced bone metabolism within the articular microenvironment. Adiponectin, an adipokine secreted by adipocytes, is involved in multiple functions, including lipid metabolism and pro-inflammatory activity. However, the mechanism of adiponectin performance within arthritic inflammation remains unclear. In this study, we observed the effect of adiponectin on the expression of oncostatin M (OSM), a pro-inflammatory cytokine, in human osteoblastic cells. Pretreatment of cells with inhibitors of phosphatidylinositol 3-kinase (PI3K), Akt, and nuclear factor (NF)-κB reduced the adiponectin-induced OSM expression in osteoblasts. Stimulation of the cells with adiponectin increased phosphorylation of PI3K, Akt, and p65. Adiponectin treatment of osteoblasts increased OSM-luciferase activity and p65 binding to NF-κB on the OSM promoter. Our results indicate that adiponectin increased OSM expression via the PI3K, Akt, and NF-κB signaling pathways in osteoblastic cells, suggesting that adiponectin is a novel target for arthritis treatment. PMID:26712749

  5. Regulation and Quality Control of Adiponectin Assembly by Endoplasmic Reticulum Chaperone ERp44*

    PubMed Central

    Hampe, Lutz; Radjainia, Mazdak; Xu, Cheng; Harris, Paul W. R.; Bashiri, Ghader; Goldstone, David C.; Brimble, Margaret A.; Wang, Yu; Mitra, Alok K.

    2015-01-01

    Adiponectin, a collagenous hormone secreted abundantly from adipocytes, possesses potent antidiabetic and anti-inflammatory properties. Mediated by the conserved Cys39 located in the variable region of the N terminus, the trimeric (low molecular weight (LMW)) adiponectin subunit assembles into different higher order complexes, e.g. hexamers (middle molecular weight (MMW)) and 12–18-mers (high molecular weight (HMW)), the latter being mostly responsible for the insulin-sensitizing activity of adiponectin. The endoplasmic reticulum (ER) chaperone ERp44 retains adiponectin in the early secretory compartment and tightly controls the oxidative state of Cys39 and the oligomerization of adiponectin. Using cellular and in vitro assays, we show that ERp44 specifically recognizes the LMW and MMW forms but not the HMW form. Our binding assays with short peptide mimetics of adiponectin suggest that ERp44 intercepts and converts the pool of fully oxidized LMW and MMW adiponectin, but not the HMW form, into reduced trimeric precursors. These ERp44-bound precursors in the cis-Golgi may be transported back to the ER and released to enhance the population of adiponectin intermediates with appropriate oxidative state for HMW assembly, thereby underpinning the process of ERp44 quality control. PMID:26060250

  6. Supplementation with conjugated linoleic acids extends the adiponectin deficit during early lactation in dairy cows.

    PubMed

    Singh, Shiva P; Häussler, Susanne; Heinz, Johanna F L; Saremi, Behnam; Mielenz, Birgit; Rehage, Jürgen; Dänicke, Sven; Mielenz, Manfred; Sauerwein, Helga

    2014-03-01

    Decreasing insulin sensitivity (IS) in peripheral tissues allows for partitioning nutrients towards the mammary gland. In dairy cows, extensive lipid mobilization and continued insulin resistance (IR) are typical for early lactation. Adiponectin, an adipokine, promotes IS. Supplementation with conjugated linoleic acids (CLA) in rodents and humans reduces fat mass whereby IR and hyperinsulinemia may occur. In dairy cows, CLA reduce milk fat, whereas body fat, serum free fatty acids and leptin are not affected. We aimed to investigate the effects of CLA supplementation on serum and adipose tissue (AT) adiponectin concentrations in dairy cows during the lactation driven and parity modulated changes of metabolism. High yielding cows (n=33) were allocated on day 1 post partum to either 100 g/day of a CLA mixture or a control fat supplement (CON) until day 182 post partum. Blood and subcutaneous (sc) AT (AT) biopsy samples were collected until day 252 post partum to measure adiponectin. Serum adiponectin decreased from day 21 pre partum reaching a nadir at calving and thereafter increased gradually. The distribution of adiponectin molecular weight forms was neither affected by time, parity nor treatment. Cows receiving CLA had decreased serum adiponectin concentrations whereby primiparous cows responded about 4 weeks earlier than multiparous cows. The time course of adiponectin concentrations in sc AT (corrected for residual blood) was similar to serum concentrations, without differences between CLA and CON. CLA supplementation attenuated the post partum increase of circulating adiponectin thus acting towards prolongation of peripartal IR and drain of nutrients towards the mammary gland.

  7. Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function After Hemorrhagic Shock.

    PubMed

    Deng, Xiyun; Cao, Yanna; Huby, Maria P; Duan, Chaojun; Baer, Lisa; Peng, Zhanglong; Kozar, Rosemary A; Doursout, Marie-Francoise; Holcomb, John B; Wade, Charles E; Ko, Tien C

    2016-01-01

    Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use of fresh frozen plasma (FFP) in patients requiring massive transfusion is associated with improved outcomes. FFP contains significant amounts of adiponectin, which is known to have vascular protective function. We hypothesize that FFP improves vascular barrier function largely via adiponectin. Plasma adiponectin levels were measured in 19 severely injured patients in hemorrhagic shock (HS). Compared with normal individuals, plasma adiponectin levels decreased to 49% in HS patients before resuscitation (P < 0.05) and increased to 64% post-resuscitation (but not significant). In a HS mouse model, we demonstrated a similar decrease in plasma adiponectin to 54% but a significant increase to 79% by FFP resuscitation compared with baseline (P < 0.05). HS disrupted lung vascular barrier function, leading to an increase in permeability. FFP resuscitation reversed these HS-induced effects. Immunodepletion of adiponectin from FFP abolished FFP's effects on blocking endothelial hyperpermeability in vitro, and on improving lung vascular barrier function in HS mice. Replenishment with adiponectin rescued FFP's effects. These findings suggest that adiponectin is an important component in FFP resuscitation contributing to the beneficial effects on vascular barrier function after HS.

  8. Adiponectin expression is decreased in the involved skin and sera of diffuse cutaneous scleroderma patients.

    PubMed

    Arakawa, Hiroki; Jinnin, Masatoshi; Muchemwa, Faith C; Makino, Takamitsu; Kajihara, Ikko; Makino, Katsunari; Honda, Noritoshi; Sakai, Keisuke; Fukushima, Satoshi; Ihn, Hironobu

    2011-09-01

    In this study, we determined the adiponectin expression in the serum and lesional skin of patients with scleroderma (SSc). Serum adiponectin concentrations were measured in 32 patients with SSc, 10 patients with SLE, 12 patients with dermatomyositis patients and 13 healthy subjects with specific enzyme-linked immunosorbent assays. Adiponectin mRNA was determined in skin tissues of five patients with diffuse cutaneous SSc (dcSSc), seven patients with limited cutaneous SSc (lcSSc) and seven healthy subjects with real-time polymerase chain reaction. There was a significant reduction in serum adiponectin levels in patients with dcSSc. SSc patients with decreased serum adiponectin levels had higher total skin thickness score and higher incidence of pulmonary fibrosis. Adiponectin mRNA levels in skin tissues from patients with dcSSc were also reduced. Serum adiponectin levels may be a useful biomarker for fibrotic condition in patients with SSc. Clarifying the role of adiponectin in collagen diseases may lead to further understanding of the pathogenesis and new therapeutic approach.

  9. Adiponectin: an independent risk factor for coronary heart disease in men in the Framingham Offspring Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our aim was to determine whether plasma adiponectin levels were an independent predictor of coronary heart disease (CHD) risk. Plasma adiponectin levels were measured in 3,188 male and female participants from cycle 6 of the Framingham Offspring Study (mean age: 57 years in both men and women; BMI:...

  10. Adiponectin receptors: a review of their structure, function and how they work.

    PubMed

    Yamauchi, Toshimasa; Iwabu, Masato; Okada-Iwabu, Miki; Kadowaki, Takashi

    2014-01-01

    The discovery of adiponectin and subsequently the receptors it acts upon have lead to a great surge forward in the understanding of the development of insulin resistance and obesity-linked diseases. Adiponectin is a hormone that is derived from adipose tissue and is reduced in obesity-linked diseases including insulin resistance/type 2 diabetes and atherosclerosis. Adiponectin exerts its effects by binding to adiponectin receptors, two of which, AdipoR1 and AdipoR2, have been cloned. This has enabled researchers to carry out detailed studies elucidating the role played by these receptors and the metabolic pathways that are involved following their activation. Such studies have clearly shown that the stimulation of these receptors is associated with glucose homeostasis and ongoing research into their role will clarify the underlying molecular mechanisms of adiponectin. Such knowledge can then be used to provide therapeutic targets aimed at managing obesity-linked diseases including type 2 diabetes and metabolic syndrome.

  11. Dietary regulation of adiponectin by direct and indirect lipid activators of nuclear hormone receptors.

    PubMed

    Rühl, R; Landrier, J F

    2016-01-01

    Adiponectin is an adipokine mainly secreted by adipocytes that presents antidiabetic, anti-inflammatory, and antiatherogenic functions. Therefore, modulation of adiponectin expression represents a promising target for prevention or treatment of several diseases including insulin resistance and type II diabetes. Pharmacological agents such as the nuclear hormone receptor synthetic agonists like peroxisome proliferator activated receptor γ agonists are of particular interest in therapeutic strategies due to their ability to increase the plasma adiponectin concentration. Nutritional approaches are also of particular interest, especially in primary prevention, since some active compounds of our diet (notably vitamins, carotenoids, or other essential nutrients) are direct or indirect lipid-activators of nuclear hormone receptors and are modifiers of adiponectin expression and secretion. The aim of the present review is to summarize current knowledge about the nutritional regulation of adiponectin by derivatives of active compounds naturally present in the diet acting as indirect or direct activators of nuclear hormone receptors.

  12. Adiponectin deficiency contributes to the development and progression of benign prostatic hyperplasia in obesity.

    PubMed

    Fu, Shi; Xu, Huan; Gu, Meng; Liu, Chong; Wang, Qiong; Wan, Xiang; Chen, Yanbo; Chen, Qi; Peng, Yubing; Cai, Zhikang; Zhou, Juan; Wang, Zhong

    2017-03-03

    The incidence of benign prostatic hyperplasia (BPH) is increasing among obese individuals, but few studies have fully explained the underlying mechanisms. We aimed to elucidate the relationship between obesity and BPH. Herein, we show that in prostatic epithelial and stromal cells, adiponectin exerts multifunctional effects including anti-proliferation, blocking of G1/S-phase progression and the promotion of apoptosis via inhibiting the MEK-ERK-p90RSK axis. Furthermore, we found that a high-fat diet (HFD) led to adiponectin deficiency and microscopic BPH in a mouse model of obesity. And an adiponectin supplement protected the obese mice from microscopic BPH. The present study provides evidence that adiponectin is a protective regulator in the development and progression of BPH and that adiponectin deficiency causally links BPH with obesity.

  13. Adult Neurogenic and Antidepressant Effects of Adiponectin: A Potential Replacement for Exercise?

    PubMed

    Li, Ang; Yau, Suk-Yu; Machado, Sergio; Yuan, Ti-Fei; So, Kwok-Fai

    2015-01-01

    Physical exercise has long been recognized to benefit locomotor and cardiovascular systems. Although an increasing body of evidence also suggests it to be an effective non-medicinal remedy for mental disorders such as depression, the underlying mechanisms remain elusive. A recent study has demonstrated that increases of the adipocyte-secreted hormone adiponectin in the central nervous system following exercise may be responsible for these neuropsychological changes, including enhanced generation of neurons in the adult hippocampus, as well as mitigation of depressive severity. The present review introduces the previously-reported functions of adult hippocampal neurogenesis and adiponectin, and discusses the potential relevance of adiponectin signaling in exercise-induced neural changes. Revealing these novel biological effects of adiponectin in the brain may help hunt reliable biomarkers to better guide the anti-depressive therapy with exercise intervention; meanwhile, pharmaceutical agents that raise endogenous levels of adiponectin or mimic its biological effects might serve as a replacement for physical exercise.

  14. Adiponectin deficiency contributes to the development and progression of benign prostatic hyperplasia in obesity

    PubMed Central

    Fu, Shi; Xu, Huan; Gu, Meng; Liu, Chong; Wang, Qiong; Wan, Xiang; Chen, Yanbo; Chen, Qi; Peng, Yubing; Cai, Zhikang; Zhou, Juan; Wang, Zhong

    2017-01-01

    The incidence of benign prostatic hyperplasia (BPH) is increasing among obese individuals, but few studies have fully explained the underlying mechanisms. We aimed to elucidate the relationship between obesity and BPH. Herein, we show that in prostatic epithelial and stromal cells, adiponectin exerts multifunctional effects including anti-proliferation, blocking of G1/S-phase progression and the promotion of apoptosis via inhibiting the MEK-ERK-p90RSK axis. Furthermore, we found that a high-fat diet (HFD) led to adiponectin deficiency and microscopic BPH in a mouse model of obesity. And an adiponectin supplement protected the obese mice from microscopic BPH. The present study provides evidence that adiponectin is a protective regulator in the development and progression of BPH and that adiponectin deficiency causally links BPH with obesity. PMID:28256562

  15. Dermal Lipogenesis Inhibits Adiponectin Production in Human Dermal Fibroblasts while Exogenous Adiponectin Administration Prevents against UVA-Induced Dermal Matrix Degradation in Human Skin

    PubMed Central

    Fang, Chien-Liang; Huang, Ling-Hung; Tsai, Hung-Yueh; Chang, Hsin-I

    2016-01-01

    Adiponectin is one of the most abundant adipokines from the subcutaneous fat, and regulates multiple activities through endocrine, paracrine, or autocrine mechanisms. However, its expression in adipogenic induced fibroblasts, and the potential role in photoaging has not been determined. Here, human dermal fibroblasts, Hs68, were presented as a cell model of dermal lipogenesis through stimulation of adipogenic differentiation medium (ADM). Similar to other studies in murine pre-adipocyte models (i.e., 3T3-L1), Hs68 fibroblasts showed a tendency to lipogenesis based on lipid accumulation, triglyceride formation, and the expressions of PPAR-γ, lipoprotein lipase (LPL), and FABP4 mRNA. As expected, ADM-treated fibroblasts displayed a reduction on adiponectin expression. Next, we emphasized the photoprotective effects of adiponectin against UVA-induced damage in Hs68 fibroblasts. UVA radiation can downregulate cell adhesion strength and elastic modulus of Hs68 fibroblasts. Moreover, UVA radiation could induce the mRNA expressions of epidermal growth factor receptor (EGFR), adiponectin receptor 1 (AdipoR1), matrix metalloproteinase-1 (MMP-1), MMP-3, and cyclooxygenase-2 (COX-2), but downregulate the mRNA expressions of type I and type III collagen. On the other hand, post-treatment of adiponectin can partially overcome UVA-induced reduction in the cell adhesion strength of Hs68 fibroblasts through the activation of AdipoR1 and the suppression of EGF-R. In addition, post-treatment of adiponectin indicated the increase of type III collagen and elastin mRNA expression and the decrease of MMP-1 and MMP-3 mRNA expression, but a limited degree of recovery of elastic modulus on UVA-irradiated Hs68 fibroblasts. Overall, these results suggest that dermal lipogenesis may inhibit the expression of adiponectin while exogenous adiponectin administration prevents against UVA-induced dermal matrix degradation in Hs68 fibroblasts. PMID:27428951

  16. Dermal Lipogenesis Inhibits Adiponectin Production in Human Dermal Fibroblasts while Exogenous Adiponectin Administration Prevents against UVA-Induced Dermal Matrix Degradation in Human Skin.

    PubMed

    Fang, Chien-Liang; Huang, Ling-Hung; Tsai, Hung-Yueh; Chang, Hsin-I

    2016-07-14

    Adiponectin is one of the most abundant adipokines from the subcutaneous fat, and regulates multiple activities through endocrine, paracrine, or autocrine mechanisms. However, its expression in adipogenic induced fibroblasts, and the potential role in photoaging has not been determined. Here, human dermal fibroblasts, Hs68, were presented as a cell model of dermal lipogenesis through stimulation of adipogenic differentiation medium (ADM). Similar to other studies in murine pre-adipocyte models (i.e., 3T3-L1), Hs68 fibroblasts showed a tendency to lipogenesis based on lipid accumulation, triglyceride formation, and the expressions of PPAR-γ, lipoprotein lipase (LPL), and FABP4 mRNA. As expected, ADM-treated fibroblasts displayed a reduction on adiponectin expression. Next, we emphasized the photoprotective effects of adiponectin against UVA-induced damage in Hs68 fibroblasts. UVA radiation can downregulate cell adhesion strength and elastic modulus of Hs68 fibroblasts. Moreover, UVA radiation could induce the mRNA expressions of epidermal growth factor receptor (EGFR), adiponectin receptor 1 (AdipoR1), matrix metalloproteinase-1 (MMP-1), MMP-3, and cyclooxygenase-2 (COX-2), but downregulate the mRNA expressions of type I and type III collagen. On the other hand, post-treatment of adiponectin can partially overcome UVA-induced reduction in the cell adhesion strength of Hs68 fibroblasts through the activation of AdipoR1 and the suppression of EGF-R. In addition, post-treatment of adiponectin indicated the increase of type III collagen and elastin mRNA expression and the decrease of MMP-1 and MMP-3 mRNA expression, but a limited degree of recovery of elastic modulus on UVA-irradiated Hs68 fibroblasts. Overall, these results suggest that dermal lipogenesis may inhibit the expression of adiponectin while exogenous adiponectin administration prevents against UVA-induced dermal matrix degradation in Hs68 fibroblasts.

  17. Adiponectin-Mediated Analgesia and Anti-Inflammatory Effects in Rat

    PubMed Central

    Iannitti, Tommaso; Graham, Annette; Dolan, Sharron

    2015-01-01

    The adipose tissue-derived protein, adiponectin, has significant anti-inflammatory properties in a variety of disease conditions. Recent evidence that adiponectin and its receptors (AdipoR1 and AdipoR2) are expressed in central nervous system, suggests that it may also have a central modulatory role in pain and inflammation. This study set out to investigate the effects of exogenously applied recombinant adiponectin (via intrathecal and intraplantar routes; 10–5000 ng) on the development of peripheral inflammation (paw oedema) and pain hypersensitivity in the rat carrageenan model of inflammation. Expression of adiponectin, AdipoR1 and AdipoR2 mRNA and protein was characterised in dorsal spinal cord using real-time polymerase chain reaction (PCR) and Western blotting. AdipoR1 and AdipoR2 mRNA and protein were found to be constitutively expressed in dorsal spinal cord, but no change in mRNA expression levels was detected in response to carrageenan-induced inflammation. Adiponectin mRNA, but not protein, was detected in dorsal spinal cord, although levels were very low. Intrathecal administration of adiponectin, both pre- and 3 hours post-carrageenan, significantly attenuated thermal hyperalgesia and mechanical hypersensitivity. Intrathecal administration of adiponectin post-carrageenan also reduced peripheral inflammation. Intraplantar administration of adiponectin pre-carrageenan dose-dependently reduced thermal hyperalgesia but had no effect on mechanical hypersensitivity and peripheral inflammation. These results show that adiponectin functions both peripherally and centrally at the spinal cord level, likely through activation of AdipoRs to modulate pain and peripheral inflammation. These data suggest that adiponectin receptors may be a novel therapeutic target for pain modulation. PMID:26352808

  18. Serum Adiponectin and Cardiometabolic Risk in Patients with Acute Coronary Syndromes

    PubMed Central

    Oliveira, Gustavo Bernardes de Figueiredo; França, João Ítalo Dias; Piegas, Leopoldo Soares

    2013-01-01

    Background The adipose tissue is considered not only a storable energy source, but mainly an endocrine organ that secretes several cytokines. Adiponectin, a novel protein similar to collagen, has been found to be an adipocyte-specific cytokine and a promising cardiovascular risk marker. Objectives To evaluate the association between serum adiponectin levels and the risk for cardiovascular events in patients with acute coronary syndromes (ACS), as well as the correlations between adiponectin and metabolic, inflammatory, and myocardial biomarkers. Methods We recruited 114 patients with ACS and a mean 1.13-year follow-up to measure clinical outcomes. Clinical characteristics and biomarkers were compared according to adiponectin quartiles. Cox proportional hazard regression models with Firth's penalization were applied to assess the independent association between adiponectin and the subsequent risk for both primary (composite of cardiovascular death/non-fatal acute myocardial infarction (AMI)/non-fatal stroke) and co-primary outcomes (composite of cardiovascular death/non-fatal AMI/non-fatal stroke/ rehospitalization requiring revascularization). Results There were significant direct correlations between adiponectin and age, HDL-cholesterol, and B-type natriuretic peptide (BNP), and significant inverse correlations between adiponectin and waist circumference, body weight, body mass index, Homeostasis Model Assessment (HOMA) index, triglycerides, and insulin. Adiponectin was associated with higher risk for primary and co-primary outcomes (adjusted HR 1.08 and 1.07/increment of 1000; p = 0.01 and p = 0.02, respectively). Conclusion In ACS patients, serum adiponectin was an independent predictor of cardiovascular events. In addition to the anthropometric and metabolic correlations, there was a significant direct correlation between adiponectin and BNP. PMID:24029961

  19. Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice

    PubMed Central

    Wang, XianFeng; Buechler, Nancy L; Yoza, Barbara K; McCall, Charles E; Vachharajani, Vidula

    2016-01-01

    Background Morbid obesity increases the cost of care in critically ill patients. Sepsis is the leading cause of death in noncoronary intensive care units. Circulating cell–endothelial cell interactions in microcirculation are the rate-determining factors in any inflammation; obesity increases these interactions further. Adiponectin deficiency is implicated in increased cardiovascular risk in obese patients. We have shown that adiponectin deficiency increases microvascular dysfunction in early sepsis. In the present study, we investigated the effect of adiponectin replacement on nutritionally obese mice with early sepsis. Methods We used cecal ligation and puncture model of sepsis in mice with diet-induced obesity (DIO) vs control diet (CTRL), with or without adiponectin treatment. We studied leukocyte/platelet adhesion in the cerebral microcirculation in early sepsis. We also studied the effect of adiponectin on free fatty acid (FFA)-fed and lipopolysaccharide-stimulated bone marrow-derived macrophages (BMDM) for mechanistic studies. Results Leukocyte and platelet adhesion increased in the cerebral microcirculation of DIO and CTRL mice with early sepsis vs. sham; moreover cell adhesion in DIO-sepsis group was significantly higher than in the CTRL-sepsis group. Adiponectin replacement decreased leukocyte/platelet adhesion in CTRL and DIO mice. In FFA-fed BMDM, adiponectin treatment decreased tumor necrosis factor-alpha mRNA expression and increased sirtuin-1 (SIRT1) mRNA expression. Furthermore, using BMDM from SIRT1 knockout mice, we showed that the adiponectin treatment decreased inflammatory response in FFA-fed BMDM via SIRT1-dependent and -independent pathways. Conclusion Adiponectin replacement attenuates microvascular inflammation in DIO-sepsis mice. Mechanistically, adiponectin treatment in FFA-fed mouse macrophages attenuates inflammatory response via SIRT1-dependent and -independent pathways. PMID:27785087

  20. Effect of weight loss on high-molecular weight adiponectin in obese children.

    PubMed

    Martos-Moreno, Gabriel Á; Barrios, Vicente; Martínez, Guillermo; Hawkins, Federico; Argente, Jesús

    2010-12-01

    Our aim was to determine the influence of weight reduction on total (T-) and high-molecular weight (HMW-) adiponectin in obese (OB) prepubertal children. Seventy OB prepubertal white patients were followed for 18 months and studied after reducing their BMI by 1 (n = 51) and 2 standard deviation scores (SDS) (n = 21) under conservative treatment, and 6 months after achieving weight loss (n = 44). Body composition dual-energy X-ray absorptiometry (DXA) and serum levels of T- and HMW-adiponectin, resistin, leptin, leptin soluble receptor (sOB-R), tumoral necrosis factor-α and interleukin-6 were determined. The control group consisted of 61 healthy prepubertal children. At diagnosis T-adiponectin was higher (P < 0.01; confidence interval (+0.04) - (+0.15)) and HMW-adiponectin lower (P < 0.001; confidence interval (-0.45) - (-0.21)) in OB children than in controls. A reduction in body fat increased T- and HMW-adiponectin and sOB-R (all P < 0.001) and decreased leptin (P < 0.001) and interleukin-6 levels (P < 0.05). After 6 months of sustained weight reduction a decrease in tumoral necrosis factor-α (P < 0.01) occurred, whereas weight recovery increased leptin (P < 0.001) and decreased T-adiponectin (P < 0.05). HMW-adiponectin levels negatively correlated with homeostasis model assessment (HOMA) index and BMI in the whole cohort (both P < 0.001), as did T-adiponectin levels and HOMA index in OB patients (P < 0.01), but neither T- nor HMW-adiponectin correlated with body fat content (BFC) in OB children. We conclude that the impairment of T- and HMW-adiponectin levels in childhood obesity is different to that in elder OB patients, showing closer relationship with carbohydrate metabolism parameters than with BFC, but increasing their levels after weight loss and in association with metabolic improvement.

  1. Association between the chondrocyte phenotype and the expression of adipokines and their receptors: evidence for a role of leptin but not adiponectin in the expression of cartilage-specific markers.

    PubMed

    Francin, Pierre-Jean; Guillaume, Cécile; Humbert, Anne-Claude; Pottie, Pascale; Netter, Patrick; Mainard, Didier; Presle, Nathalie

    2011-11-01

    Although extensive evidence support the key role of adipokines in cartilage homeostasis, contradictory data have been found for their expression and their effects in chondrocytes. This study was then undertaken to determine whether a phenotypic modulation may affect the expression of adipokines and their receptors in human chondrocytes. The expression of leptin, adiponectin and their receptors, as well as cartilage-specific genes was examined in chondrocytes obtained from patients with osteoarthritis either directly after cells harvest or after culture in monolayer or in alginate beads. The results showed major changes in the gene expression pattern after culture in monolayer with a shift from the adipokines to their receptors. Interestingly, this downregulation of adipokines was associated with a loss of chondrocyte phenotype, and chondrocytes recovered a cartilage-like expression profile of leptin and adiponectin when cultured in a tridimensional chondrocyte phenotype-inducing system, but ceased expressing their receptors. Further experiments clearly showed that leptin but not adiponectin promoted the expression of cartilage-specific markers through mitogen-activated protein kinase, Janus kinase and phosphatidylinositol-3 kinase signaling pathways. In conclusion, our data indicate that any phenotypic modulation could affect chondrocyte responsiveness to leptin or adiponectin, and provide evidence for an important role for leptin in regulating the expression of cartilage-specific markers.

  2. Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease?

    PubMed Central

    2014-01-01

    Adiponectin is the most abundant peptide secreted by adipocytes, being a key component in the interrelationship between adiposity, insulin resistance and inflammation. Central obesity accompanied by insulin resistance is a key factor in the development of metabolic syndrome (MS) and future macrovascular complications. Moreover, the remarkable correlation between coronary artery disease (CAD) and alterations in glucose metabolism has raised the likelihood that atherosclerosis and type 2 diabetes mellitus (T2DM) may share a common biological background. We summarize here the current knowledge about the influence of adiponectin on insulin sensitivity and endothelial function, discussing its forthcoming prospects and potential role as a therapeutic target for MS, T2DM, and cardiovascular disease. Adiponectin is present in the circulation as a dimer, trimer or protein complex of high molecular weight hexamers, >400 kDa. AdipoR1 and AdipoR2 are its major receptors in vivo mediating the metabolic actions. Adiponectin stimulates phosphorylation and AMP (adenosin mono phosphate) kinase activation, exerting direct effects on vascular endothelium, diminishing the inflammatory response to mechanical injury and enhancing endothelium protection in cases of apolipoprotein E deficiency. Hypoadiponectinemia is consistently associated with obesity, MS, atherosclerosis, CAD, T2DM. Lifestyle correction helps to favorably modify plasma adiponectin levels. Low adiponectinemia in obese patients is raised via continued weight loss programs in both diabetic and nondiabetic individuals and is also accompanied by reductions in pro-inflammatory factors. Diet modifications, like intake of fish, omega-3 supplementation, adherence to a Mediterranean dietary pattern and coffee consumption also increase adiponectin levels. Antidiabetic and cardiovascular pharmacological agents, like glitazones, glimepiride, angiotensin converting enzyme inhibitors and angiotensin receptor blockers are also able to

  3. Adiponectin Receptor Signaling on Dendritic Cells Blunts Antitumor Immunity

    PubMed Central

    Tan, Peng H.; Tyrrell, Helen E.J.; Gao, Liquan; Xu, Danmei; Quan, Jianchao; Gill, Dipender; Rai, Lena; Ding, Yunchuan; Plant, Gareth; Chen, Yuan; Xue, John Z.; Handa, Ashok I.; Greenall, Michael J.; Walsh, Kenneth; Xue, Shao-An

    2015-01-01

    Immune escape is a fundamental trait of cancer. Dendritic cells (DC) that interact with T cells represent a crucial site for the development of tolerance to tumor antigens, but there remains incomplete knowledge about how DC-tolerizing signals evolve during tumorigenesis. In this study, we show that DCs isolated from patients with metastatic or locally advanced breast cancer express high levels of the adiponectin receptors AdipoR1 and AdipoR2, which are sufficient to blunt antitumor immunity. Mechanistic investigations of ligand–receptor interactions on DCs revealed novel signaling pathways for each receptor. AdipoR1 stimulated IL10 production by activating the AMPK and MAPKp38 pathways, whereas AdipoR2 modified inflammatory processes by activating the COX-2 and PPARγ pathways. Stimulation of these pathways was sufficient to block activation of NF-κB in DC, thereby attenuating their ability to stimulate antigen-specific T-cell responses. Together, our findings reveal novel insights into how DC-tolerizing signals evolve in cancer to promote immune escape. Furthermore, by defining a critical role for adiponectin signaling in this process, our work suggests new and broadly applicable strategies for immunometabolic therapy in patients with cancer. PMID:25261236

  4. Molecular mechanisms of diabetes and atherosclerosis: role of adiponectin.

    PubMed

    Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro

    2012-06-01

    Type 2 diabetes mellitus (T2DM) is a disease characterized by inadequate beta-cell response due to progressive insulin resistance that typically accompanies physical inactivity and weight gain. T2DM is associated with substantial morbidity and mortality related to the associated atherosclerotic cardiovascular risks and diabetic vasculopathies, including microangiopathies (e.g., blindness and renal failure) and macroangiopathies (atherosclerosis). The increasing global prevalence of T2DM is linked to the rising rates of obesity, especially abdominal obesity. Visceral fat accumulation is upstream of obesity-related disorders including atherosclerotic cardiovascular disease (ACVD), and is associated with impaired insulin sensitivity and atherosclerosis through dysregulated production of adipocytokines, especially hypoadiponectinemia. This review article discusses the pathophysiological mechanisms responsible for T2DM and atherosclerosis, focusing on adiponectin. Clinical and experimental studies have shown that hypoadiponectinemia contributes to a variety of life style-related diseases including T2DM and atherosclerosis. It is likely that life-style modification, visceral fat reduction and use of medications that increase serum adiponectin levels (e.g., rimonabant, thiazolidinediones, fibrates, angiotensin receptor blocker and mineralocorticoid receptor blockade) when provided in combination can improve hypoadiponectinemia and thus prevent the development of life style-related diseases including T2DM and ACVD.

  5. Circulating Adiponectin Levels Following Treatment Can Predict Late Clinical Outcomes in Chronic Heart Failure

    PubMed Central

    Yu, Ho-Ping; Jen, Hsu-Lung; Yin, Wei-Hsian; Wei, Jeng

    2017-01-01

    Background Circulating adiponectin concentration increases in patients with chronic heart failure (HF). We sought to explore the prognostic value of temporal changes in adiponectin concentration following treatment for chronic HF. Methods Serum adiponectin levels were measured at baseline and after a 3-month anti-failure treatment in 124 patients with symptomatic chronic systolic HF. Major adverse cardiac events (MACE) including death, heart transplantation, or hospitalization with worsening HF during a median follow-up period of 752 days were determined. Results Univariate and multivariate analysis showed that high levels of adiponectin after a 3-month treatment were associated with a 3.8-fold increased risk of MACE (p = 0.03), independent of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Moreover, the combining of circulating levels of adiponectin with NT-proBNP provided independent and additional prognostic value in identifying high risk patients with MACE during follow-up. Conclusions Changes in adiponectin and NT-proBNP over time provide prognostic information. When adiponectin is used in conjunction with NT-proBNP in chronic HF, the prognostic value may be better than if each biomarker is used separately. PMID:28344417

  6. Promotion of adiponectin multimerization by emodin: a novel AMPK activator with PPARγ-agonist activity.

    PubMed

    Chen, Zhifen; Zhang, Lu; Yi, Junyang; Yang, Zhuanbo; Zhang, Zhijie; Li, Zhen

    2012-11-01

    Adiponectin is an important insulin-sensitizing adipokine with multiple beneficial effects on obesity-associated medical complications. It is secreted from adipocytes into circulation as high, medium, and low molecular weight forms (HMW, MMW, and LMW). Each oligomeric form of adiponectin exerts non-overlapping biological functions, with the HMW oligomer possessing the most potent insulin-sensitizing activity. In this study, we reported that emodin, a natural product and active ingredient of various Chinese herbs, activates AMPK in both 3T3-L1 adipocytes and 293T cells. Activation of AMPK by emodin promotes the assembly of HMW adiponectin and increases the ratio of HMW adiponectin to total adiponectin in 3T1-L1 adipocytes. Emodin might activate AMPK by an indirect mechanism similar to berberine. We also found that emodin activates PPARγ and promotes differentiation and adiponectin expression during differentiation of 3T3-L1 preadipocytes. Therefore, emodin is a novel AMPK activator with PPARγ-agonist activity. Our results demonstrate that the effects of emodin on adiponectin expression and multimerization are the ultimate effects resulting from both AMPK activation and PPARγ activation. The dual-activity makes emodin or the derivatives potential drug candidates for the treatment of type 2 diabetes and other obesity-related metabolic diseases.

  7. Exendin-4 Upregulates Adiponectin Level in Adipocytes via Sirt1/Foxo-1 Signaling Pathway

    PubMed Central

    Wang, Anping; Li, Ting; An, Ping; Yan, Wenhua; Zheng, Hua; Wang, Baoan; Mu, Yiming

    2017-01-01

    Glucagon-like peptide-1 (GLP-1) receptor plays an essential role in regulating glucose metabolism. GLP-1 receptor agonists have been widely used for treating diabetes and other insulin resistance-related diseases. However, mechanisms underlying the anti-diabetic effects of GLP-1 receptor agonists remain largely unknown. In this study, we investigated the effects of GLP-1 agonist exendin-4 on the expression of adiponectin, an insulin sensitizing hormone. We found that exendin-4 increased the expression and secretion of adiponectin both in vitro and in vivo. Our data showed that exendin-4 upregulated adiponectin expression at both mRNA and protein levels in adipocytes and adipose tissues. The effects of exendin-4 on adiponectin expression were dependent on the GLP-1 receptor. We further demonstrated important roles of Sirt1 and transcriptional factor Foxo-1 in mediating the function of exendin-4 in regulating adiponectin expression. Suppression of Sirt1 or Foxo-1 expression significantly impaired exendin-4-induced adiponectin expression. Consistently, exendin-4 up-regulated Sirt1 and Foxo-1 expression in vivo. Our work is the first study demonstrating the role of Sirt1/Foxo-1 in regulating the regulatory function of a GLP-1 receptor agonist in adiponectin expression both in vitro and in vivo. The results provide important information for the mechanism underlying the function of GLP-1R on improving insulin resistance and related diseases. PMID:28122026

  8. Beneficial effects of adiponectin on periodontal ligament cells under normal and regenerative conditions.

    PubMed

    Nokhbehsaim, Marjan; Keser, Sema; Nogueira, Andressa Vilas Boas; Cirelli, Joni Augusto; Jepsen, Søren; Jäger, Andreas; Eick, Sigrun; Deschner, James

    2014-01-01

    Type 2 diabetes and obesity are increasing worldwide and linked to periodontitis, a chronic disease which is characterized by the irreversible destruction of the tooth-supporting tissues, that is, periodontium. The mechanisms underlying the association of diabetes mellitus and obesity with periodontal destruction and compromised periodontal healing are not well understood, but decreased plasma levels of adiponectin, as found in diabetic and obese individuals, might be a critical mechanistic link. The aim of this in vitro study was to examine the effects of adiponectin on periodontal ligament (PDL) cells under normal and regenerative conditions, and to study the regulation of adiponectin and its receptors in these cells. Adiponectin stimulated significantly the expression of growth factors and extracellular matrix, proliferation, and in vitro wound healing, reduced significantly the constitutive tumor necrosis factor-α expression, and caused a significant upregulation of its own expression. The beneficial actions of enamel matrix derivative on a number of PDL cell functions critical for periodontal regeneration were partially enhanced by adiponectin. The periodontopathogen Porphyromonas gingivalis inhibited the adiponectin expression and stimulated the expression of its receptors. In conclusion, reduced levels of adiponectin, as found in type 2 diabetes and obesity, may compromise periodontal health and healing.

  9. The effect of low calorie diet on adiponectin concentration: a systematic review and meta-analysis.

    PubMed

    Salehi-Abargouei, A; Izadi, V; Azadbakht, L

    2015-07-01

    Adiponectin secreted from adipose tissue is proposed to be inversely related to the body fat mass. However, the magnitude of the effect of low calorie diet on adiponectin concentrations remains unknown. The present study was aimed to conduct a systematic review and meta-analysis on clinical trials that access the effect of low calorie diet on adiponectin concentration. We searched PubMed, SCOPUS, ISI web of science, and Google scholar for RCTs until January 2015. Totally, 13 trials were found, which examined the effect of low calorie diet on adiponectin concentration compared control group without low calorie diet.Our meta-analysis showed that weight loss diet can substantially increase the adiponectin concentration in overall (Hedges' g=0.34, 95% CI:0.17-0.50, p<0.001). Subgroup analysis also revealed that the low calorie diet can substantially enhance adiponectin concentrations when prescribed for ≤16 weeks (Hedges' g=0.48, 95% CI: 0.12-0.83, p=0.01) compared to >16 weeks (Hedges' g=0.30, 95% CI: 0.11-0.48, p=0.002). Weight loss diet beneficially affects blood adiponectin concentrations. More clinical trials are recommended to clear this effect among different genders and nationalities, and assess the magnitude of the effect based on changes in fat mass.

  10. Serum Adiponectin is Associated with Adverse Outcomes of Asthma in Men but Not in Women

    PubMed Central

    Sood, Akshay; Dominic, Elizabeth; Qualls, Clifford; Steffes, Michael W.; Thyagarajan, Bharat; Smith, Lewis J.; Lewis, Cora E.; Jacobs, David R.

    2011-01-01

    Background: Murine studies suggest a beneficial effect of systemic adiponectin on asthma. Our objective was to determine the association between serum adiponectin concentrations and asthma control/severity outcomes in men and women separately. Methods: Cross-sectional and longitudinal analyses of data from years 10, 15, and 20 examinations of the prospective coronary artery risk development in young adults study in the United States were performed. Asthma was defined by self-reported provider diagnosis at or prior to year 15 examination. Outcomes included presence of active disease, number of respiratory symptoms, and number of asthma medications; as well as longitudinal decline in absolute FEV1. Year 15 serum adiponectin concentration was the predictor variable. Results: In a multivariable analysis of 411 eligible subjects, after adjusting for body mass index and covariates, higher serum adiponectin concentrations were associated with more frequent active disease (including more frequent use of any asthma medication), and greater number of respiratory symptoms and asthma medications among men but not among women with asthma (p for interactions between sex and adiponectin for all analyses < 0.05). Conclusions: Higher serum adiponectin concentrations may be independently associated with adverse clinical outcomes of asthma in men but not in women. If biological effect is confirmed in future studies, modification of systemic adiponectin concentrations may open up newer ways to treat asthma in men. PMID:22007173

  11. Adiponectin and the mediation of HDL-cholesterol change with improved lifestyle: the Look AHEAD Study.

    PubMed

    Belalcazar, L Maria; Lang, Wei; Haffner, Steven M; Hoogeveen, Ron C; Pi-Sunyer, F Xavier; Schwenke, Dawn C; Balasubramanyam, Ashok; Tracy, Russell P; Kriska, Andrea P; Ballantyne, Christie M

    2012-12-01

    Adipose tissue dysfunction plays a key role in the development of the metabolic abnormalities characteristic of type 2 diabetes (T2DM) and participates actively in lipid metabolism. Adiponectin, found abundantly in circulation and a marker of adipose health, is decreased in obese persons with T2DM. We investigated whether the changes in adiponectin with an intensive lifestyle intervention (ILI) for weight loss could potentially mediate the increase in low HDL-cholesterol (HDL-C) with ILI. Adiponectin and its fractions were determined using an ELISA with selective protease treatment in 1,397 participants from Look AHEAD, a trial examining whether ILI will reduce cardiovascular events in overweight/obese subjects with T2DM when compared with a control arm, diabetes support and education (DSE). Multivariable regression and mediational analyses were performed for adiponectin and its high-molecular-weight (HMW) and non-HMW fractions. ILI increased baseline HDL-C by 9.7% and adiponectin by 11.9%; changes with DSE were 1.3% and 0.2%, respectively (P < 0.0001). In a model including changes in weight, fitness, triglycerides, and glucose control and that adjusted for demographics and medical history, adiponectin changes remained significantly associated with HDL-C change. Data supported the contribution of changes in both HMW- and non-HMW-adiponectin to the improvement in HDL-C with ILI.

  12. Effects of aging on the plasma levels of nesfatin-1 and adiponectin

    PubMed Central

    LI, JIANG-BO; NISHIDA, MIYUKI; KAIMOTO, KAORI; ASAKAWA, AKIHIRO; CHAOLU, HUHE; CHENG, KAI-CHUN; LI, YING-XIAO; TERASHI, MUTSUMI; KOYAMA, KEN ICHIRO; AMITANI, HARUKA; SAKOGUCHI, TAKEO; USHIKAI, MIHARU; IKEDA, SATOSHI; AOYAMA, KOHJI; HORIUCHI, MASAHISA; LI, JIAN-ZHONG; INUI, AKIO

    2014-01-01

    Gastric and adipose tissue secrete a number of hormones that are involved in energy metabolism. The biological functions of these hormones, including their effects on aging, are currently under investigation. Adiponectin was shown to be directly involved in appetite and the control of body weight. However, the effects of aging of nesfatin-1, an appetite-suppressing peptide that was recently identified, have not yet been fully elucidated. The aim of this study was to determine the effects of aging on the plasma levels of nesfatin-1 and adiponectin. Our results demonstrated no significant differences in the nesfatin-1 plasma levels among three age groups (2, 6 and 24 months) of female BALB/c mice. The plasma nesfatin-1 levels/visceral fat (VF) ratio in the 24-month-old mice was significantly lower compared to that in the 2- and 6-month-old mice. In addition, there were no significant differences in the plasma adiponectin levels among the three age groups. The plasma adiponectin levels/VF ratio in the 24-month-old mice was significantly lower compared to that in the 2- and 6-month-old mice. In conclusion, there were no age-related changes in the plasma levels of nesfatin-1 and adiponectin, although the ratio of plasma levels of nesfatin-1 and adiponectin per VF was decreased with advancing age. Our results indicated that nesfatin-1 and adiponectin may be involved in controlling energy balance during aging. PMID:24649088

  13. The role of leptin/adiponectin ratio in metabolic syndrome and diabetes.

    PubMed

    López-Jaramillo, Patricio; Gómez-Arbeláez, Diego; López-López, Jose; López-López, Cristina; Martínez-Ortega, Javier; Gómez-Rodríguez, Andrea; Triana-Cubillos, Stefany

    2014-04-01

    The metabolic syndrome comprises a cluster of cardiometabolic risk factors, with insulin resistance and adiposity as its central features. Identifying individuals with metabolic syndrome is important due to its association with an increased risk of coronary heart disease and type 2 diabetes mellitus. Attention has focused on the visceral adipose tissue production of cytokines (adipokines) in metabolic syndrome and type 2 diabetes mellitus, as the levels of the anti-inflammatory adipokine adiponectin are decreased, while proinflammatory cytokines are elevated, creating a proinflammatory state associated with insulin resistance and endothelial dysfunction. In this review, we will give special attention to the role of the leptin/adiponectin ratio. We have previously demonstrated that in individuals with severe coronary artery disease, abdominal obesity was uniquely related to decreased plasma concentrations of adiponectin and increased leptin levels. Leptin/adiponectin imbalance was associated with increased waist circumference and a decreased vascular response to acetylcholine and increased vasoconstriction due to angiotensin II. Leptin and adiponectin have opposite effects on subclinical inflammation and insulin resistance. Leptin upregulates proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6; these are associated with insulin resistance and type 2 diabetes mellitus. In contrast, adiponectin has anti-inflammatory properties and downregulates the expression and release of a number of proinflammatory immune mediators. Therefore, it appears that interactions between angiotensin II and leptin/adiponectin imbalance may be important mediators of the elevated risk of developing type 2 diabetes mellitus and cardiovascular diseases associated with abdominal obesity.

  14. Adiponectin Deficiency Leads to Female Subfertility and Ovarian Dysfunctions in Mice.

    PubMed

    Cheng, Lixian; Shi, Hui; Jin, Yan; Li, Xiaoxi; Pan, Jinshun; Lai, Yimei; Lin, Yan; Jin, Ya; Roy, Gaurab; Zhao, Allan; Li, Fanghong

    2016-12-01

    Adipose tissue plays an important role in regulating female fertility, owing to not only its energy stores but also the endocrine actions of secreted adipokines. As one of the adipokines, adiponectin is almost exclusively secreted from the fat, and its circulating concentration is paradoxically reduced in obesity. Although recent studies implied a purported positive role of adiponectin in ovarian functions, definitive in vivo evidence has been sorely lacking. We have consistently observed subfertility in female adiponectin null mice and therefore postulated a protective role of adiponectin in ovarian functions. Female adiponectin null mice displayed impaired fertility, reduced retrieval of oocytes, disrupted estrous cycle, elevated number of atretic follicles, and impaired late folliculogenesis. Analysis of their sera revealed a significant decrease in estradiol and FSH but an increase in LH and testosterone at proestrus. In addition, we found marked reduction of progesterone levels at diestrus, a significant decrease in LH receptor expression as well as in the number of GnRH immunoreactive neurons. Adiponectin deficiency also altered the peak concentrations of LH surge and led to lower expression of Cytochrome P450 family 11 subfamily A member 1 (P450scc), an enzyme critical for progesterone synthesis, as well as an increase in BCL2 associated X, apoptosis regulator and Insulin like growth factor binding protein 4 in atretic follicles. These physiological and molecular events were independent of insulin sensitivity. Thus, we have revealed a novel mechanism linking adiponectin and female fertility that entails regulation of reproductive hormone balance and ovarian follicle development.

  15. Ubiquitin specific protease 2 acts as a key modulator for the regulation of cell cycle by adiponectin and leptin in cancer cells.

    PubMed

    Nepal, Saroj; Shrestha, Anup; Park, Pil-Hoon

    2015-09-05

    Adiponectin and leptin, both produced from adipose tissue, cause cell cycle arrest and progression, respectively in cancer cells. Ubiquitin specific protease-2 (USP-2), a deubiquitinating enzyme, is known to impair proteasome-induced degradation of cyclin D1, a critical cell cycle regulator. Herein, we investigated the effects of these adipokines on USP-2 expression and its potential role in the modulation of cell cycle. Treatment with globular adiponectin (gAcrp) decreased, whereas leptin increased USP-2 expression both in human hepatoma and breast cancer cells. In addition, overexpression or gene silencing of USP-2 affected cyclin D1 expression and cell cycle progression/arrest by adipokines. Adiponectin and leptin also modulated in vitro proteasomal activity, which was partially dependent on USP-2 expression. Taken together, our results reveal that modulation of USP-2 expression plays a crucial role in cell cycle regulation by adipokines. Thus, USP-2 would be a promising therapeutic target for the modulation of cancer cell growth by adipokines.

  16. The Role of Alcohol Consumption in Regulating Circulating Levels of Adiponectin: A Prospective Cohort Study

    PubMed Central

    Britton, Annie

    2015-01-01

    Context: The role of alcohol intake in influencing longitudinal trajectories of adiponectin is unclear. Objective: The objective of the study was to examine the association between alcohol intake and changes in the circulating levels of adiponectin over repeat measures. Design, Setting, and Participants: A prospective cohort study of 2855 men and women (74% men with a mean age of 50 y at baseline) drawn from the Whitehall II study. Data from study phases 3 (1991–1993), 5 (1997–1999), and 7 (2002–2004) were used. Main Outcome Measure: Adiponectin serum concentrations (nanograms per milliliter) were measured, and alcohol intake was defined in terms of number of UK units (1 U = 8 g ethanol) consumed in the previous 7 days on three occasions. Cross-sectional associations between alcohol and adiponectin levels were calculated using linear regression. A bivariate dual-change score model was used to estimate the effect of alcohol intake on upcoming change in adiponectin. Models were adjusted for age, sex, ethnicity, and smoking status. Results: Alcohol consumption was cross-sectionally associated with (log transformed) adiponectin levels (β ranging from .001 to .004, depending on phase and level of adjustment) but was not associated with changes in adiponectin levels over time [γ = −0.002 (SE 0.002), P = 0.246]. Conclusion: Alcohol intake is not associated with changes in circulating adiponectin levels in this cohort. This finding provides evidence that adiponectin levels are unlikely to mediate the relationship between moderate alcohol consumption and reduced risk of type 2 diabetes. It is important to consider dynamic longitudinal relationships rather than cross-sectional associations. PMID:26000546

  17. Higher Circulating Adiponectin Levels Are Associated with Increased Risk of Atrial Fibrillation in Older Adults

    PubMed Central

    Macheret, Fima; Bartz, Traci M.; Djousse, Luc; Ix, Joachim H.; Mukamal, Kenneth J.; Zieman, Susan J.; Siscovick, David S.; Tracy, Russell P.; Heckbert, Susan R.; Psaty, Bruce M.; Kizer, Jorge R.

    2016-01-01

    Background Adiponectin has cardioprotective properties, suggesting that lower levels seen in obesity and diabetes could heighten risk of atrial fibrillation (AF). Among older adults, however, higher adiponectin has been linked to greater incidence of adverse outcomes associated with AF, although recent reports have shown this association to be U-shaped. We postulated that higher adiponectin would be linked to increased risk for AF in older adults in a U-shaped manner. Methods We examined the associations of total and high-molecular-weight (HMW) adiponectin with incident AF among individuals free of prevalent cardiovascular disease (CVD) participating in a population-based cohort study of older adults (n=3190; age=74±5 years). Results During median follow-up of 11.4 years, there were 886 incident AF events. Adjusted cubic splines showed a positive and linear association between adiponectin and incident AF. After adjusting for potential confounders, including amino-terminal pro-B-type natriuretic peptide 1–76, the hazard ratio (95% CI) for AF per SD increase in total adiponectin was 1.14 (1.05–1.24), while that for HMW adiponectin was 1.17 (1.08–1.27). Additional adjustment for putative mediators, including subclinical CVD, diabetes, lipids, and inflammation, did not significantly affect these estimates. Conclusions The present findings demonstrate that higher, not lower, levels of adiponectin are independently associated with increased risk of AF in older adults despite its documented cardiometabolic benefits. Additional work is necessary to determine if adiponectin is a marker of failed counter-regulatory pathways or whether this hormone is directly harmful in the setting of or as a result of advanced age. PMID:25855796

  18. Associations of adiponectin with individual European ancestry in African Americans: the Jackson Heart Study

    PubMed Central

    Bidulescu, Aurelian; Choudhry, Shweta; Musani, Solomon K.; Buxbaum, Sarah G.; Liu, Jiankang; Rotimi, Charles N.; Wilson, James G.; Taylor, Herman A.; Gibbons, Gary H.

    2014-01-01

    Background: Compared with European Americans, African Americans (AAs) exhibit lower levels of the cardio-metabolically protective adiponectin even after accounting for adiposity measures. Because few studies have examined in AA the association between adiponectin and genetic admixture, a dense panel of ancestry informative markers (AIMs) was used to estimate the individual proportions of European ancestry (PEA) for the AAs enrolled in a large community-based cohort, the Jackson Heart Study (JHS). We tested the hypothesis that plasma adiponectin and PEA are directly associated and assessed the interaction with a series of cardio-metabolic risk factors. Methods: Plasma specimens from 1439 JHS participants were analyzed by ELISA for adiponectin levels. Using pseudo-ancestral population genotype data from the HapMap Consortium, PEA was estimated with a panel of up to 1447 genome-wide preselected AIMs by a maximum likelihood approach. Interaction assessment, stepwise linear and cubic multivariable-adjusted regression models were used to analyze the cross-sectional association between adiponectin and PEA. Results: Among the study participants (62% women; mean age 48 ± 12 years), the median (interquartile range) of PEA was 15.8 (9.3)%. Body mass index (BMI) (p = 0.04) and insulin resistance (p = 0.0001) modified the association between adiponectin and PEA. Adiponectin was directly and linearly associated with PEA (β = 0.62 ± 0.28, p = 0.03) among non-obese (n = 673) and insulin sensitive participants (n = 1141; β = 0.74 ± 0.23, p = 0.001), but not among those obese or with insulin resistance. No threshold point effect was detected for non-obese participants. Conclusions: In a large AA population, the individual proportion of European ancestry was linearly and directly associated with plasma adiponectin among non-obese and non insulin-resistant participants, pointing to the interaction of genetic and metabolic factors influencing adiponectin levels. PMID:24575123

  19. The rapid increase of circulating adiponectin in neonatal calves depends on colostrum intake.

    PubMed

    Kesser, J; Hill, M; Heinz, J F L; Koch, C; Rehage, J; Steinhoff-Wagner, J; Hammon, H M; Mielenz, B; Sauerwein, H; Sadri, H

    2015-10-01

    Adiponectin, an adipokine, regulates metabolism and insulin sensitivity. Considering that the transplacental transfer of maternal proteins of high molecular weight is hindered in ruminants, this study tested the hypothesis that the blood concentration of adiponectin in neonatal calves largely reflects their endogenous synthesis whereby the intake of colostrum might modify the circulating concentrations. We thus characterized the adiponectin concentrations in neonatal and young calves that were fed either colostrum or formula. Three trials were performed: in trial 1, 20 calves were all fed colostrum for 3 d, and then formula until weaning. Blood samples were collected on d 0 (before colostrum feeding), and on d 1, 3, 11, 22, 34, 43, 52, 70, 90, and 108 postnatum. In trial 2, 14 calves were studied for the first 4 d of life. They were fed colostrum (n=7) or formula (n=7), and blood samples were taken right after birth and before each morning feeding on d 2, 3, and 4. In trial 3, calves born preterm (n=7) or at term received colostrum only at 24 h postnatum. Blood was sampled at birth, and before and 2 h after feeding. Additionally, allantoic fluid and blood from 4 Holstein cows undergoing cesarean section were sampled. Adiponectin was quantified by ELISA. In trial 1, the serum adiponectin concentrations recorded on d 3 were 4.7-fold higher than before colostrum intake. The distribution of the molecular weight forms of adiponectin differed before and after colostrum consumption. In trial 2, the colostrum group had consistently greater plasma adiponectin concentrations than the formula group after the first meal. In trial 3, the preterm calves tended to have lower concentrations of plasma adiponectin than the term calves at birth and before and 2 h after feeding. Furthermore, the adiponectin concentrations were substantially lower in allantoic fluid than in the sera from neonatal calves and from cows at parturition. Our results show that calves are born with very low

  20. Adiponectin resistance in skeletal muscle: pathophysiological implications in chronic heart failure

    PubMed Central

    Van Berendoncks, An M; Hoymans, Vicky Y; Vrints, Christiaan J

    2015-01-01

    Abstract Skeletal muscle wasting is a common complication of chronic heart failure (CHF) and linked to poor patient prognosis. In recent years, adiponectin was postulated to be centrally involved in CHF‐associated metabolic failure and muscle wasting. This review discusses current knowledge on the role of adiponectin in CHF. Particular emphasis will be given to the complex interaction mechanisms and the intracellular pathways underlying adiponectin resistance in skeletal muscle of CHF patients. In this review, we propose that the resistance process is multifactorial, integrating abnormalities emanating from insulin signalling, mitochondrial biogenesis, and ceramide metabolism. PMID:27239409

  1. Muscle-specific overexpression of AdipoR1 or AdipoR2 gives rise to common and discrete local effects whilst AdipoR2 promotes additional systemic effects

    PubMed Central

    Keshvari, Sahar; Henstridge, Darren C.; Ng, Choaping; Febbraio, Mark A.; Whitehead, Jonathan P.

    2017-01-01

    Hypoadiponectinemia and adiponectin resistance are implicated in the aetiology of obesity-related cardiometabolic disorders, hence represent a potential therapeutic axis. Here we characterised the effects of in vivo electrotransfer-mediated overexpression of the adiponectin receptors, AdipoR1 or AdipoR2, into tibialis anterior muscle (TAM) of lean or obese mice. In lean mice, TAM-specific overexpression of AdipoR1 (TAMR1) or AdipoR2 (TAMR2) increased phosphorylation of AMPK, AKT and ERK and expression of the insulin responsive glucose transporter glut4. In contrast, only TAMR2 increased pparα and a target gene acox1. These effects were decreased in obese mice despite no reduction in circulating adiponectin levels. TAMR2 also increased expression of adipoQ in TAM of lean and obese mice. Furthermore, in obese mice TAMR2 promoted systemic effects including; decreased weight gain; reduced epididymal fat mass and inflammation; increased epididymal adipoQ expression; increased circulating adiponectin. Collectively, these results demonstrate that AdipoR1 and AdipoR2 exhibit overlapping and distinct effects in skeletal muscle consistent with enhanced adiponectin sensitivity but these appear insufficient to ameliorate established obesity-induced adiponectin resistance. We also identify systemic effects upon TAMR2 in obese mice and postulate these are mediated by altered myokine production. Further studies are warranted to investigate this possibility which may reveal novel therapeutic approaches. PMID:28145500

  2. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

    PubMed

    Dastani, Zari; Hivert, Marie-France; Timpson, Nicholas; Perry, John R B; Yuan, Xin; Scott, Robert A; Henneman, Peter; Heid, Iris M; Kizer, Jorge R; Lyytikäinen, Leo-Pekka; Fuchsberger, Christian; Tanaka, Toshiko; Morris, Andrew P; Small, Kerrin; Isaacs, Aaron; Beekman, Marian; Coassin, Stefan; Lohman, Kurt; Qi, Lu; Kanoni, Stavroula; Pankow, James S; Uh, Hae-Won; Wu, Ying; Bidulescu, Aurelian; Rasmussen-Torvik, Laura J; Greenwood, Celia M T; Ladouceur, Martin; Grimsby, Jonna; Manning, Alisa K; Liu, Ching-Ti; Kooner, Jaspal; Mooser, Vincent E; Vollenweider, Peter; Kapur, Karen A; Chambers, John; Wareham, Nicholas J; Langenberg, Claudia; Frants, Rune; Willems-Vandijk, Ko; Oostra, Ben A; Willems, Sara M; Lamina, Claudia; Winkler, Thomas W; Psaty, Bruce M; Tracy, Russell P; Brody, Jennifer; Chen, Ida; Viikari, Jorma; Kähönen, Mika; Pramstaller, Peter P; Evans, David M; St Pourcain, Beate; Sattar, Naveed; Wood, Andrew R; Bandinelli, Stefania; Carlson, Olga D; Egan, Josephine M; Böhringer, Stefan; van Heemst, Diana; Kedenko, Lyudmyla; Kristiansson, Kati; Nuotio, Marja-Liisa; Loo, Britt-Marie; Harris, Tamara; Garcia, Melissa; Kanaya, Alka; Haun, Margot; Klopp, Norman; Wichmann, H-Erich; Deloukas, Panos; Katsareli, Efi; Couper, David J; Duncan, Bruce B; Kloppenburg, Margreet; Adair, Linda S; Borja, Judith B; Wilson, James G; Musani, Solomon; Guo, Xiuqing; Johnson, Toby; Semple, Robert; Teslovich, Tanya M; Allison, Matthew A; Redline, Susan; Buxbaum, Sarah G; Mohlke, Karen L; Meulenbelt, Ingrid; Ballantyne, Christie M; Dedoussis, George V; Hu, Frank B; Liu, Yongmei; Paulweber, Bernhard; Spector, Timothy D; Slagboom, P Eline; Ferrucci, Luigi; Jula, Antti; Perola, Markus; Raitakari, Olli; Florez, Jose C; Salomaa, Veikko; Eriksson, Johan G; Frayling, Timothy M; Hicks, Andrew A; Lehtimäki, Terho; Smith, George Davey; Siscovick, David S; Kronenberg, Florian; van Duijn, Cornelia; Loos, Ruth J F; Waterworth, Dawn M; Meigs, James B; Dupuis, Josee; Richards, J Brent; Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur; Dina, Christian; Welch, Ryan P; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S; Thorleifsson, Gudmar; McCulloch, Laura J; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J; Raychaudhuri, Soumya; McCarroll, Steve A; Hofmann, Oliver M; Segrè, Ayellet V; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L; Boström, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noël P; Charpentier, Guillaume; Chines, Peter S; Cornelis, Marilyn; Crawford, Gabe; Doney, Alex S F; Elliott, Katherine S; Elliott, Amanda L; Erdos, Michael R; Fox, Caroline S; Franklin, Christopher S; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U; Johnson, Paul R V; Jørgensen, Torben; Kao, Wen H L; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Payne, Felicity; Petersen, Ann-Kristin; Platou, Carl; Proença, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, N William; Robertson, Neil R; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J; Saxena, Richa; Shields, Beverley M; Shrader, Peter; Sigurdsson, Gunnar; Sparsø, Thomas; Strassburger, Klaus; Stringham, Heather M; Sun, Qi; Swift, Amy J; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M; van Haeften, Timon W; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V; Walters, G Bragi; Weedon, Michael N; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N; Cauchi, Stephane; Collins, Francis S; Gloyn, Anna L; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A; Hitman, Graham A; Hofman, Albert; Hunter, David J; Hveem, Kristian; Laakso, Markku; Morris, Andrew D; Palmer, Colin N A; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Watanabe, Richard M; Abecasis, Goncalo R; Boehm, Bernhard O; Campbell, Harry; Daly, Mark J; Hattersley, Andrew T; Pedersen, Oluf; Barroso, Inês; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I; Soranzo, Nicole; Wheeler, Eleanor; Glazer, Nicole L; Bouatia-Naji, Nabila; Mägi, Reedik; Randall, Joshua; Elliott, Paul; Rybin, Denis; Dehghan, Abbas; Hottenga, Jouke Jan; Song, Kijoung; Goel, Anuj; Lajunen, Taina; Doney, Alex; Cavalcanti-Proença, Christine; Kumari, Meena; Timpson, Nicholas J; Zabena, Carina; Ingelsson, Erik; An, Ping; O'Connell, Jeffrey; Luan, Jian'an; Elliott, Amanda; McCarroll, Steven A; Roccasecca, Rosa Maria; Pattou, François; Sethupathy, Praveen; Ariyurek, Yavuz; Barter, Philip; Beilby, John P; Ben-Shlomo, Yoav; Bergmann, Sven; Bochud, Murielle; Bonnefond, Amélie; Borch-Johnsen, Knut; Böttcher, Yvonne; Brunner, Eric; Bumpstead, Suzannah J; Chen, Yii-Der Ida; Chines, Peter; Clarke, Robert; Coin, Lachlan J M; Cooper, Matthew N; Crisponi, Laura; Day, Ian N M; de Geus, Eco J C; Delplanque, Jerome; Fedson, Annette C; Fischer-Rosinsky, Antje; Forouhi, Nita G; Franzosi, Maria Grazia; Galan, Pilar; Goodarzi, Mark O; Graessler, Jürgen; Grundy, Scott; Gwilliam, Rhian; Hallmans, Göran; Hammond, Naomi; Han, Xijing; Hartikainen, Anna-Liisa; Hayward, Caroline; Heath, Simon C; Hercberg, Serge; Hillman, David R; Hingorani, Aroon D; Hui, Jennie; Hung, Joe; Kaakinen, Marika; Kaprio, Jaakko; Kesaniemi, Y Antero; Kivimaki, Mika; Knight, Beatrice; Koskinen, Seppo; Kovacs, Peter; Kyvik, Kirsten Ohm; Lathrop, G Mark; Lawlor, Debbie A; Le Bacquer, Olivier; Lecoeur, Cécile; Li, Yun; Mahley, Robert; Mangino, Massimo; Martínez-Larrad, María Teresa; McAteer, Jarred B; McPherson, Ruth; Meisinger, Christa; Melzer, David; Meyre, David; Mitchell, Braxton D; Mukherjee, Sutapa; Naitza, Silvia; Neville, Matthew J; Orrù, Marco; Pakyz, Ruth; Paolisso, Giuseppe; Pattaro, Cristian; Pearson, Daniel; Peden, John F; Pedersen, Nancy L; Pfeiffer, Andreas F H; Pichler, Irene; Polasek, Ozren; Posthuma, Danielle; Potter, Simon C; Pouta, Anneli; Province, Michael A; Rayner, Nigel W; Rice, Kenneth; Ripatti, Samuli; Rivadeneira, Fernando; Rolandsson, Olov; Sandbaek, Annelli; Sandhu, Manjinder; Sanna, Serena; Sayer, Avan Aihie; Scheet, Paul; Seedorf, Udo; Sharp, Stephen J; Shields, Beverley; Sigurðsson, Gunnar; Sijbrands, Eric J G; Silveira, Angela; Simpson, Laila; Singleton, Andrew; Smith, Nicholas L; Sovio, Ulla; Swift, Amy; Syddall, Holly; Syvänen, Ann-Christine; Tönjes, Anke; Uitterlinden, André G; van Dijk, Ko Willems; Varma, Dhiraj; Visvikis-Siest, Sophie; Vitart, Veronique; Vogelzangs, Nicole; Waeber, Gérard; Wagner, Peter J; Walley, Andrew; Ward, Kim L; Watkins, Hugh; Wild, Sarah H; Willemsen, Gonneke; Witteman, Jaqueline C M; Yarnell, John W G; Zelenika, Diana; Zethelius, Björn; Zhai, Guangju; Zhao, Jing Hua; Zillikens, M Carola; Borecki, Ingrid B; Meneton, Pierre; Magnusson, Patrik K E; Nathan, David M; Williams, Gordon H; Silander, Kaisa; Bornstein, Stefan R; Schwarz, Peter; Spranger, Joachim; Karpe, Fredrik; Shuldiner, Alan R; Cooper, Cyrus; Serrano-Ríos, Manuel; Lind, Lars; Palmer, Lyle J; Hu, Frank B; Franks, Paul W; Ebrahim, Shah; Marmot, Michael; Kao, W H Linda; Pramstaller, Peter Paul; Wright, Alan F; Stumvoll, Michael; Hamsten, Anders; Buchanan, Thomas A; Valle, Timo T; Rotter, Jerome I; Penninx, Brenda W J H; Boomsma, Dorret I; Cao, Antonio; Scuteri, Angelo; Schlessinger, David; Uda, Manuela; Ruokonen, Aimo; Jarvelin, Marjo-Riitta; Peltonen, Leena; Mooser, Vincent; Sladek, Robert; Musunuru, Kiran; Smith, Albert V; Edmondson, Andrew C; Stylianou, Ioannis M; Koseki, Masahiro; Pirruccello, James P; Chasman, Daniel I; Johansen, Christopher T; Fouchier, Sigrid W; Peloso, Gina M; Barbalic, Maja; Ricketts, Sally L; Bis, Joshua C; Feitosa, Mary F; Orho-Melander, Marju; Melander, Olle; Li, Xiaohui; Li, Mingyao; Cho, Yoon Shin; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young; Park, Taesung; Kim, Kyunga; Sim, Xueling; Ong, Rick Twee-Hee; Croteau-Chonka, Damien C; Lange, Leslie A; Smith, Joshua D; Ziegler, Andreas; Zhang, Weihua; Zee, Robert Y L; Whitfield, John B; Thompson, John R; Surakka, Ida; Spector, Tim D; Smit, Johannes H; Sinisalo, Juha; Scott, James; Saharinen, Juha; Sabatti, Chiara; Rose, Lynda M; Roberts, Robert; Rieder, Mark; Parker, Alex N; Pare, Guillaume; O'Donnell, Christopher J; Nieminen, Markku S; Nickerson, Deborah A; Montgomery, Grant W; McArdle, Wendy; Masson, David; Martin, Nicholas G; Marroni, Fabio; Lucas, Gavin; Luben, Robert; Lokki, Marja-Liisa; Lettre, Guillaume; Launer, Lenore J; Lakatta, Edward G; Laaksonen, Reijo; Kyvik, Kirsten O; König, Inke R; Khaw, Kay-Tee; Kaplan, Lee M; Johansson, Åsa; Janssens, A Cecile J W; Igl, Wilmar; Hovingh, G Kees; Hengstenberg, Christian; Havulinna, Aki S; Hastie, Nicholas D; Harris, Tamara B; Haritunians, Talin; Hall, Alistair S; Groop, Leif C; Gonzalez, Elena; Freimer, Nelson B; Erdmann, Jeanette; Ejebe, Kenechi G; Döring, Angela; Dominiczak, Anna F; Demissie, Serkalem; Deloukas, Panagiotis; de Faire, Ulf; Crawford, Gabriel; Chen, Yii-der I; Caulfield, Mark J; Boekholdt, S Matthijs; Assimes, Themistocles L; Quertermous, Thomas; Seielstad, Mark; Wong, Tien Y; Tai, E-Shyong; Feranil, Alan B; Kuzawa, Christopher W; Taylor, Herman A; Gabriel, Stacey B; Holm, Hilma; Gudnason, Vilmundur; Krauss, Ronald M; Ordovas, Jose M; Munroe, Patricia B; Kooner, Jaspal S; Tall, Alan R; Hegele, Robert A; Kastelein, John J P; Schadt, Eric E; Strachan, David P; Reilly, Muredach P; Samani, Nilesh J; Schunkert, Heribert; Cupples, L Adrienne; Sandhu, Manjinder S; Ridker, Paul M; Rader, Daniel J; Kathiresan, Sekar

    2012-01-01

    Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

  3. Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals

    PubMed Central

    Tanaka, Toshiko; Morris, Andrew P.; Small, Kerrin; Isaacs, Aaron; Beekman, Marian; Coassin, Stefan; Lohman, Kurt; Qi, Lu; Kanoni, Stavroula; Pankow, James S.; Uh, Hae-Won; Wu, Ying; Bidulescu, Aurelian; Rasmussen-Torvik, Laura J.; Greenwood, Celia M. T.; Ladouceur, Martin; Grimsby, Jonna; Manning, Alisa K.; Liu, Ching-Ti; Kooner, Jaspal; Mooser, Vincent E.; Vollenweider, Peter; Kapur, Karen A.; Chambers, John; Wareham, Nicholas J.; Langenberg, Claudia; Frants, Rune; Willems-vanDijk, Ko; Oostra, Ben A.; Willems, Sara M.; Lamina, Claudia; Winkler, Thomas W.; Psaty, Bruce M.; Tracy, Russell P.; Brody, Jennifer; Chen, Ida; Viikari, Jorma; Kähönen, Mika; Pramstaller, Peter P.; Evans, David M.; St. Pourcain, Beate; Sattar, Naveed; Wood, Andrew R.; Bandinelli, Stefania; Carlson, Olga D.; Egan, Josephine M.; Böhringer, Stefan; van Heemst, Diana; Kedenko, Lyudmyla; Kristiansson, Kati; Nuotio, Marja-Liisa; Loo, Britt-Marie; Harris, Tamara; Garcia, Melissa; Kanaya, Alka; Haun, Margot; Klopp, Norman; Wichmann, H.-Erich; Deloukas, Panos; Katsareli, Efi; Couper, David J.; Duncan, Bruce B.; Kloppenburg, Margreet; Adair, Linda S.; Borja, Judith B.; Wilson, James G.; Musani, Solomon; Guo, Xiuqing; Johnson, Toby; Semple, Robert; Teslovich, Tanya M.; Allison, Matthew A.; Redline, Susan; Buxbaum, Sarah G.; Mohlke, Karen L.; Meulenbelt, Ingrid; Ballantyne, Christie M.; Dedoussis, George V.; Hu, Frank B.; Liu, Yongmei; Paulweber, Bernhard; Spector, Timothy D.; Slagboom, P. Eline; Ferrucci, Luigi; Jula, Antti; Perola, Markus; Raitakari, Olli; Florez, Jose C.; Salomaa, Veikko; Eriksson, Johan G.; Frayling, Timothy M.; Hicks, Andrew A.; Lehtimäki, Terho; Smith, George Davey; Siscovick, David S.; Kronenberg, Florian; van Duijn, Cornelia; Loos, Ruth J. F.; Waterworth, Dawn M.; Meigs, James B.; Dupuis, Josee; Richards, J. Brent

    2012-01-01

    Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8–1.2×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10−4). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10−3, n = 22,044), increased triglycerides (p = 2.6×10−14, n = 93,440), increased waist-to-hip ratio (p = 1.8×10−5, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10−3, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10−13, n = 96,748) and decreased BMI (p = 1.4×10−4, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance. PMID:22479202

  4. Associations of Adiponectin with Adiposity, Insulin Sensitivity, and Diet in Young, Healthy, Mexican Americans and Non-Latino White Adults.

    PubMed

    Pereira, Rocio I; Low Wang, Cecilia C; Wolfe, Pamela; Havranek, Edward P; Long, Carlin S; Bessesen, Daniel H

    2015-12-22

    Low circulating adiponectin levels may contribute to higher diabetes risk among Mexican Americans (MA) compared to non-Latino whites (NLW). Our objective was to determine if among young healthy adult MAs have lower adiponectin than NLWs, independent of differences in adiposity. In addition, we explored associations between adiponectin and diet. This was an observational, cross-sectional study of healthy MA and NLW adults living in Colorado (U.S.A.). We measured plasma total adiponectin, adiposity (BMI, and visceral adipose tissue), insulin sensitivity (IVGTT), and self-reported dietary intake in 43 MA and NLW adults. Mean adiponectin levels were 40% lower among MA than NLW (5.8 ± 3.3 vs. 10.7 ± 4.2 µg/mL, p = 0.0003), and this difference persisted after controlling for age, sex, BMI, and visceral adiposity. Lower adiponectin in MA was associated with lower insulin sensitivity (R² = 0.42, p < 0.01). Lower adiponectin was also associated with higher dietary glycemic index, lower intake of vegetables, higher intake of trans fat, and higher intake of grains. Our findings confirm that ethnic differences in adiponectin reflect differences in insulin sensitivity, but suggest that these are not due to differences in adiposity. Observed associations between adiponectin and diet support the need for future studies exploring the regulation of adiponectin by diet and other environmental factors.

  5. Associations of Adiponectin with Adiposity, Insulin Sensitivity, and Diet in Young, Healthy, Mexican Americans and Non-Latino White Adults

    PubMed Central

    Pereira, Rocio I.; Low Wang, Cecilia C.; Wolfe, Pamela; Havranek, Edward P.; Long, Carlin S.; Bessesen, Daniel H.

    2015-01-01

    Low circulating adiponectin levels may contribute to higher diabetes risk among Mexican Americans (MA) compared to non-Latino whites (NLW). Our objective was to determine if among young healthy adult MAs have lower adiponectin than NLWs, independent of differences in adiposity. In addition, we explored associations between adiponectin and diet. This was an observational, cross-sectional study of healthy MA and NLW adults living in Colorado (U.S.A.). We measured plasma total adiponectin, adiposity (BMI, and visceral adipose tissue), insulin sensitivity (IVGTT), and self-reported dietary intake in 43 MA and NLW adults. Mean adiponectin levels were 40% lower among MA than NLW (5.8 ± 3.3 vs. 10.7 ± 4.2 µg/mL, p = 0.0003), and this difference persisted after controlling for age, sex, BMI, and visceral adiposity. Lower adiponectin in MA was associated with lower insulin sensitivity (R2 = 0.42, p < 0.01). Lower adiponectin was also associated with higher dietary glycemic index, lower intake of vegetables, higher intake of trans fat, and higher intake of grains. Our findings confirm that ethnic differences in adiponectin reflect differences in insulin sensitivity, but suggest that these are not due to differences in adiposity. Observed associations between adiponectin and diet support the need for future studies exploring the regulation of adiponectin by diet and other environmental factors. PMID:26703682

  6. Integral role of PTP1B in adiponectin-mediated inhibition of oncogenic actions of leptin in breast carcinogenesis.

    PubMed

    Taliaferro-Smith, LaTonia; Nagalingam, Arumugam; Knight, Brandi Brandon; Oberlick, Elaine; Saxena, Neeraj K; Sharma, Dipali

    2013-01-01

    The molecular effects of obesity are mediated by alterations in the levels of adipocytokines. High leptin level associated with obese state is a major cause of breast cancer progression and metastasis, whereas adiponectin is considered a "guardian angel adipocytokine" for its protective role against various obesity-related pathogenesis including breast cancer. In the present study, investigating the role of adiponectin as a potential inhibitor of leptin, we show that adiponectin treatment inhibits leptin-induced clonogenicity and anchorage-independent growth. Leptin-stimulated migration and invasion of breast cancer cells is also effectively inhibited by adiponectin. Analyses of the underlying molecular mechanisms reveal that adiponectin suppresses activation of two canonical signaling molecules of leptin signaling axis: extracellular signal-regulated kinase (ERK) and Akt. Pretreatment of breast cancer cells with adiponectin protects against leptin-induced activation of ERK and Akt. Adiponectin increases expression and activity of the physiological inhibitor of leptin signaling, protein tyrosine phosphatase 1B (PTP1B), which is found to be integral to leptin-antagonist function of adiponectin. Inhibition of PTP1B blocks adiponectin-mediated inhibition of leptin-induced breast cancer growth. Our in vivo studies show that adenovirus-mediated adiponectin treatment substantially reduces leptin-induced mammary tumorigenesis in nude mice. Exploring therapeutic strategies, we demonstrate that treatment of breast cancer cells with rosiglitazone results in increased adiponectin expression and inhibition of migration and invasion. Rosiglitazone treatment also inhibits leptin-induced growth of breast cancer cells. Taken together, these data show that adiponectin treatment can inhibit the oncogenic actions of leptin through blocking its downstream signaling molecules and raising adiponectin levels could be a rational therapeutic strategy for breast carcinoma in obese patients

  7. Evolving role of adiponectin in cancer-controversies and update

    PubMed Central

    Katira, Arnav; Tan, Peng H.

    2016-01-01

    Adiponectin (APN), an adipokine produced by adipocytes, has been shown to have a critical role in the pathogenesis of obesity-associated malignancies. Through its receptor interactions, APN may exert its anti-carcinogenic effects including regulating cell survival, apoptosis and metastasis via a plethora of signalling pathways. Despite the strong evidence supporting this notion, some work may indicate otherwise. Our review addresses all controversies critically. On the whole, hypoadiponectinaemia is associated with increased risk of several malignancies and poor prognosis. In addition, various genetic polymorphisms may predispose individuals to increased risk of obesity-associated malignancies. We also provide an updated summary on therapeutic interventions to increase APN levels that are of key interest in this field. To date efforts to manipulate APN levels have been promising, but much work remains to be done. PMID:27144066

  8. Role of Adiponectin and Its Receptors in Cancer

    PubMed Central

    Obeid, Stephanie; Hebbard, Lionel

    2012-01-01

    Adiponectin (APN), a novel hormone/cytokine derived from adipocyte tissue, is involved in various physiological functions. Genetics, nutrition, and adiposity are factors contributing to circulating plasma concentrations of APN. Clinical correlation studies have shown that lower levels of serum APN are associated with increased malignancy of various cancers, such as breast and colon cancers, suggesting that APN has a role in tumorigenesis. APN affects insulin resistance, thus further influencing cancer development. Tumor cells may express receptors for APN. Cellular signaling is the mechanism by which APN exerts its host-protective responses. These factors suggest that serum APN levels and downstream signaling targets of APN may serve as potential diagnostic markers for malignancies. Further research is necessary to clarify the exact role of APN in cancer diagnosis and therapy. PMID:23691481

  9. Adiponectin: an attractive marker for metabolic disorders in Chronic Obstructive Pulmonary Disease (COPD).

    PubMed

    Bianco, Andrea; Mazzarella, Gennaro; Turchiarelli, Viviana; Nigro, Ersilia; Corbi, Graziamaria; Scudiero, Olga; Sofia, Matteo; Daniele, Aurora

    2013-10-14

    Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung disease which may be complicated by development of co-morbidities including metabolic disorders. Metabolic disorders commonly associated with this disease contribute to lung function impairment and mortality. Systemic inflammation appears to be a major factor linking COPD to metabolic alterations. Adipose tissue seems to interfere with systemic inflammation in COPD patients by producing a large number of proteins, known as "adipokines", involved in various processes such as metabolism, immunity and inflammation. There is evidence that adiponectin is an important modulator of inflammatory processes implicated in airway pathophysiology. Increased serum levels of adiponectin and expression of its receptors on lung tissues of COPD patients have recently highlighted the importance of the adiponectin pathway in this disease. Further, in vitro studies have demonstrated an anti-inflammatory activity for this adipokine at the level of lung epithelium. This review focuses on mechanisms by which adiponectin is implicated in linking COPD with metabolic disorders.

  10. Adiponectin serum levels correlate with insulin resistance in type 2 diabetic patients

    PubMed Central

    Aleidi, Shereen; Issa, Ala; Bustanji, Haidar; Khalil, Mohammad; Bustanji, Yasser

    2014-01-01

    The adipose tissue is not only an inert storage depot for lipids, but also it secretes a variety of bioactive molecules, known as adipokines, which affect whole-body homeostasis. Adiponectin is the most abundant of these adipocytokines and is known to have a regulatory effect on the metabolism of glucose and lipid. The main objectives of this study were to evaluate the serum levels of adiponectin and to establish a correlation between adiponectin serum levels and the degree of insulin resistance in type 2 diabetic patients. Eighty participants were enrolled in this study; 61 type 2 diabetic patients and 19 apparently healthy subjects. Serum level of adiponectin was measured by enzyme-linked immunosorbent assay (ELISA) for each participant. Data collection sheet was filled with all required information for each participant. Adiponectin level in the diabetic patients (5.05 ± 2.61 μg/ml) was lower than in non-diabetic healthy controls (5.71 ± 2.35 μg/ml). When the results were compared according to gender, diabetic females showed significantly higher adiponectin levels (5.76 ± 2.64 μg/ml) than diabetic males (4.366 ± 2.43 μg/ml, P = 0.035). In addition, female diabetic patients with abdominal obesity (waist circumference (WC) ⩾ 88 cm) had lower adiponectin levels (5.58 ± 2.58 μg/ml) than diabetic females without abdominal obesity (6.96 ± 3.12 μg/ml). The correlation analysis indicated that adiponectin had a significant positive correlation with age (r = −0.450, P < 0.001). In conclusion, female diabetic patients had a statistically significant higher adiponectin level than male diabetic patients which could indicate a gender effect. Adiponectin levels were inversely related to insulin resistance; as patients with abdominal obesity had lower serum levels of adiponectin. PMID:26106273

  11. Relationship of serum adiponectin and resistin to glucose intolerance and fat topography in south-Asians

    PubMed Central

    Wasim, Hanif; Al-Daghri, Nasser M; Chetty, Raja; McTernan, Phillip G; Barnett, A H; Kumar, Sudhesh

    2006-01-01

    Objectives South-Asians have lower adiponectin levels compared to Caucasians. It was not clear however, if this intrinsic feature is related to aspects of glucose metabolism. This study aims to determine the relationship between body fat distribution and adipocytokine in South-Asian subjects by measuring serum adipocytokines, adiposity, insulinemia, and glucose tolerance levels. Methods In this cross-sectional study, 150 South-Asians (80 males, 70 females) were included, 60 had NGT (Control group, Age 51.33 ± 11.5, BMI 27 ± 2.3), 60 had IGT (Age 57.7 ± 12.5, BMI 27.2 ± 2.7), 30 had type 2 DM (Age 49.5 ± 10.9, BMI 28 ± 1.7). Measures of adiposity, adipocytokines and other metabolic parameters were determined. Parameters were measured using the following: a) Plasma glucose by glucose oxidase method b) CRP by immunoturbidimetric method (Roche/Hitachi analyser) c) insulin by Medgenix INS-ELISA immunoenzymetric assay by Biosource (Belgium) d) Leptin, Adiponectin by radioimmunoassay kits by Linco Research (St. Charles MO) e) Resistin by immunoassay kits by Phoenix Pharmaceuticals INC (530 Harbor Boulevard, Belmont CA 94002, USA). Results Adiponectin concentrations were highest in NGT, decreased in IGT and lowest in DMT2, (both p < 0.01). Leptin was significantly higher in DMT2 than IGT and NGT p = 0.02 and 0.04 respectively. There was a significant positive relationships between log adiponectin and 2-hr insulin values, p = 0.028 and history of hypertensions and a ischemic heart disease p = 0.008 with R = 0.65. There was a significant inverse correlation between log adiponectin and resistin, p < 0.01. Conclusion Resistin levels had an inverse correlation with adiponectin levels, indicating an inverse relationship between pro-inflammatory cytokines and adiponectin. Adiponectin levels were related to glucose tolerance. PMID:16669997

  12. Plasma adiponectin concentrations are associated with dietary glycemic index in Malaysian patients with type 2 diabetes.

    PubMed

    Loh, Beng-In; Sathyasuryan, Daniel Robert; Mohamed, Hamid Jan Jan

    2013-01-01

    Adiponectin, an adipocyte-derived hormone has been implicated in the control of blood glucose and chronic inflammation in type 2 diabetes. However, limited studies have evaluated dietary factors on plasma adiponectin levels, especially among type 2 diabetic patients in Malaysia. The aim of this study was to investigate the influence of dietary glycemic index on plasma adiponectin concentrations in patients with type 2 diabetes. A cross-sectional study was conducted in 305 type 2 diabetic patients aged 19-75 years from the Penang General Hospital, Malaysia. Socio-demographic information was collected using a standard questionnaire while dietary details were determined by using a pre-validated semi-quantitative food frequency questionnaire. Anthropometry measurement included weight, height, BMI and waist circumference. Plasma adiponectin concentrations were measured using a commercial ELISA kit. Data were analyzed using multiple linear regression. After multivariate adjustment, dietary glycemic index was inversely associated with plasma adiponectin concentrations (β =-0.272, 95% CI -0.262, - 0.094; p<0.001). It was found that in individuals who consumed 1 unit of foods containing high dietary glycemic index that plasma adiponectin level reduced by 0.3 μg/mL. Thirty two percent (31.9%) of the variation in adiponectin concentrations was explained by age, sex, race, smoking status, BMI, waist circumference, HDL-C, triglycerides, magnesium, fiber and dietary glycemic index according to the multiple linear regression model (R2=0.319). These results support the hypothesis that dietary glycemic index influences plasma adiponectin concentrations in patients with type 2 diabetes. Controlled clinical trials are required to confirm our findings and to elucidate the underlying mechanism.

  13. Insulin-independent role of adiponectin receptor signaling in Drosophila germline stem cell maintenance.

    PubMed

    Laws, Kaitlin M; Sampson, Leesa L; Drummond-Barbosa, Daniela

    2015-03-15

    Adipocytes have key endocrine roles, mediated in large part by secreted protein hormones termed adipokines. The adipokine adiponectin is well known for its role in sensitizing peripheral tissues to insulin, and several lines of evidence suggest that adiponectin might also modulate stem cells/precursors. It remains unclear, however, how adiponectin signaling controls stem cells and whether this role is secondary to its insulin-sensitizing effects or distinct. Drosophila adipocytes also function as an endocrine organ and, although no obvious adiponectin homolog has been identified, Drosophila AdipoR encodes a well-conserved homolog of mammalian adiponectin receptors. Here, we generate a null AdipoR allele and use clonal analysis to demonstrate an intrinsic requirement for AdipoR in germline stem cell (GSC) maintenance in the Drosophila ovary. AdipoR null GSCs are not fully responsive to bone morphogenetic protein ligands from the niche and have a slight reduction in E-cadherin levels at the GSC-niche junction. Conversely, germline-specific overexpression of AdipoR inhibits natural GSC loss, suggesting that reduction in adiponectin signaling might contribute to the normal decline in GSC numbers observed over time in wild-type females. Surprisingly, AdipoR is not required for insulin sensitization of the germline, leading us to speculate that insulin sensitization is a more recently acquired function than stem cell regulation in the evolutionary history of adiponectin signaling. Our findings establish Drosophila female GSCs as a new system for future studies addressing the molecular mechanisms whereby adiponectin receptor signaling modulates stem cell fate.

  14. Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension.

    PubMed

    Furuhashi, Masato; Ura, Nobuyuki; Higashiura, Katsuhiro; Murakami, Hideyuki; Tanaka, Marenao; Moniwa, Norihito; Yoshida, Daisuke; Shimamoto, Kazuaki

    2003-07-01

    Adiponectin, an adipocyte-derived protein, has been suggested to play an important role in insulin sensitivity. We examined the association between insulin sensitivity (M value) evaluated by the euglycemic-hyperinsulinemic glucose clamp and adiponectin concentrations in 30 essential hypertensives (EHT) and 20 normotensives (NT) and investigated the effect of blockade of the renin-angiotensin system (RAS) on adiponectin concentrations. EHT were divided into 12 insulin-resistant EHT (EHT-R) and 18 non-insulin-resistant EHT (EHT-N) using mean-1 SD of the M value in NT. There were no intergroup differences in age, gender, and body mass index (BMI). EHT-R had significantly higher levels of insulin and triglyceride and lower levels of adiponectin than did NT and EHT-N. EHT-R had higher levels of free fatty acid and lower levels of high-density lipoprotein (HDL) cholesterol than did EHT-N. Adiponectin concentrations were positively correlated with M value and HDL cholesterol and negatively correlated with BMI, insulin, free fatty acid, and triglyceride but not with blood pressure. M value, BMI, and HDL cholesterol were independent determinants of adiponectin concentrations in multiple and stepwise regression analyses. Sixteen EHT were treated with an angiotensin-converting enzyme inhibitor (temocapril, 4 mg/d; n=9) or an angiotensin II receptor blocker (candesartan, 8 mg/d; n=7) for 2 weeks. Treatment with temocapril or candesartan significantly decreased blood pressure and increased M value and adiponectin concentrations but did not affect BMI and HDL cholesterol. These results suggest that hypoadiponectinemia is related to insulin resistance in essential hypertension and that RAS blockade increases adiponectin concentrations with improvement in insulin sensitivity.

  15. High-molecular-weight adiponectin does not predict cardiovascular events in patients with type 2 diabetes.

    PubMed

    Krzyzanowska, Katarzyna; Aso, Yoshimasa; Mittermayer, Friedrich; Inukai, Toshihiko; Brix, Johanna; Schernthaner, Guntram

    2009-04-01

    Low circulating high-molecular-weight (HMW) adiponectin might be associated with increased cardiovascular risk. This study aimed to investigate the relationship between HMW adiponectin and cardiovascular events in patients with type 2 diabetes mellitus (T2DM) with an adverse cardiovascular risk profile. The investigation took place in a specialized outpatient clinic for metabolic diseases and included 147 patients with T2DM following a cross-sectional and a prospective study protocol. Ninety patients had macrovascular disease at baseline defined as preexisting coronary artery disease, previous stroke, or peripheral artery disease. HMW adiponectin measured by enzyme-linked immunosorbent assay (Fujirebio, Tokyo, Japan) and routine clinical parameters were determined in all patients at baseline. The occurrence of new cardiovascular events (myocardial infarction, stroke, and all-cause mortality) during the follow-up period was evaluated. No significant correlations between traditional cardiovascular risk markers and HMW adiponectin could be detected. HMW adiponectin did not differ between subjects with and without macrovascular disease at baseline (3.5 [interquartile range [IQR]: 2.2-5.7] mg/L vs 4.0 [IQR: 2.5-7.1] mg/L). During a follow-up of 19.3 (IQR: 16-25) months, 61 endpoints (41 myocardial infarctions, 10 strokes, and 10 deaths) were observed. A 1-standard-deviation increment of log-transformed HMW adiponectin was not significantly associated with the occurrence of cardiovascular events (Adjusted hazard ratio [HR]: 0.95; 95% confidence interval [CI]: 0.58-1.54; P = 0.835). In conclusion, HMW adiponectin was not related to present macrovascular disease and is not associated with future cardiovascular events in high-risk patients with T2DM. It is unlikely that HMW adiponectin has significant vasoprotective effects in these patients.

  16. Adiponectin plasma levels are increased by atorvastatin treatment in subjects at high cardiovascular risk.

    PubMed

    Blanco-Colio, Luis M; Martín-Ventura, Jose L; Gómez-Guerrero, Carmen; Masramon, Xavier; de Teresa, Eduardo; Farsang, Csaba; Gaw, Allan; Gensini, GianFranco; Leiter, Lawrence A; Langer, Anatoly; Egido, Jesús

    2008-05-31

    Adiponectin can suppress atherogenesis by inhibiting the adherence of monocytes, reducing their phagocytic activity, and suppressing the accumulation of modified lipoproteins in the vascular wall. Contradictory data have been reported about the effect of statins on adiponectin plasma levels. In this work, adiponectin plasma levels were measured in 102 statin-free subjects from the Spanish population of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study, a 12-week, prospective, multi-centre, open-label trial which enrolled subjects with coronary heart disease, coronary heart disease-equivalent or a 10-year coronary heart disease risk >20%. Subjects were assigned to atorvastatin (10-80 mg/day) based on low-density lipoprotein (LDL)-cholesterol concentration at screening. For comparison, age and gender-matched blood donors (N=40) were used as controls. Control subjects did not present hypertension, hypercholesterolemia, diabetes, metabolic syndrome and history of cardiovascular diseases. Adiponectin levels were diminished in patients at high cardiovascular risk compared with control subjects [4166 (3661-4740) vs 5806 (4764-7075) ng/ml respectively; geometric mean (95% CI); P<0.0001]. In the whole population, atorvastatin treatment increased adiponectin levels [9.7 (3.2-16.7);% Change (95% CI); P=0.003]. This increment was in a dose-dependent manner; maximal effect observed with atorvastatin 80 mg/d [24.7 (5.7-47.1); P=0.01]. Adiponectin concentrations were positively correlated with high-density lipoprotein-cholesterol both before and after atorvastatin treatment. No association was observed between adiponectin and LDL-cholesterol before and after atorvastatin treatment. In conclusion, atorvastatin increased adiponectin plasma levels in subjects at high cardiovascular risk, revealing a novel anti-inflammatory effect of this drug.

  17. CTX Correlation to Disease Duration and Adiponectin in Egyptian Children with T1DM

    PubMed Central

    Hashim, Amel A.; Emara, Ibrahim A.; El-Hefnawy, Mohamed H.

    2016-01-01

    Summary Background In this study, we investigated the relationship of adiponectin with bone marker changes in Egyptian children and adolescents with T1DM and the effect of disease duration on these markers, as well as the possible correlations between adiponectin and bone markers in these patients. Methods Sixty Egyptian children and adolescent patients with T1DM were studied. Serum adiponectin and collagen breakdown products (cross-linked C-terminal telopeptide of collagen type l »CTX«) were measured and compared to the results of 20 age-matched healthy controls. Results After adjustment for age, BMI, Tanner stage and gender; (total) adiponectin was significantly higher in all T1DM patients. Serum level of CTX and 25(OH)D showed a marked decrease in diabetics with disease duration > 5 years. Serum level of (total) calcium and inorganic phosphorus (Pi) did not show significant difference from control. CTX was inversely correlated to FBG and T1DM duration. Pi was inversely, while 25(OH)D was directly correlated to FBG. Total calcium showed an inverse correlation with HbA1c. FBG, TC, TAG, LDL-C were independent predictors of CTX in T1DM. Conclusions Adiponectin showed no correlation with either CTX or bone homeostatic indices. FBG, TC, TAG, LDL-C were independent predictors of CTX in T1DM. We recommend further investigation of adiponectin isoforms in a population-based study, to establish a good age- and sex-related reference.

  18. Relationship of Plasma Adiponectin and Waist-hip Ratio with Coronary Artery Disease

    PubMed Central

    Rashiti, Premtim; Elezi, Shpend; Behluli, Ibrahim; Mucaj, Sefedin

    2016-01-01

    Background: This study aimed to investigate correlation between adiponectin and waist-hip-ratio with severity of coronary artery disease (CAD). There is uncertainty about the association between circulating concentrations of adiponectin and CAD. Methods: We enrolled eighty-two consecutive patients undergoing non-urgent coronary angiography for CAD survey. According to the angiography results, the patients were divided into two groups in 1:1 ratio patients admitted with a diagnosis of CAD and non-CAD. We conducted hospital based research, involving study group with documented angiographically CAD, and control group without evidence of CAD. Angiograms were also quantified for the extent and severity of CAD by the Gensini scoring system. We measured baseline adiponectin levels in stored serum samples of all patients, anthropometric and biochemical risk factors were assessed in both groups. Results: The presence of CAD was associated with current smoking, male gender, waist–hip ratio (WHR) and left ventricular ejection fraction (LVEF). Baseline adiponectin concentrations correlated significantly in terms of the lipid parameters, positively with HDL cholesterol concentrations (r=0.327, P=0.028, P<0.05) and serum triglyceride concentrations were correlated negatively (r=-0.513, P<0.001). No significant difference between median adiponectin levels at baseline was observed between cases and controls. Conclusion: There is a significant positive correlation between waist–hip ratio and presence and severity of coronary artery disease. In conclusion, there is a significant positive correlation between adiponectin and Gensini score among Kosovar patients. PMID:28210011

  19. Adiponectin and resistin: a role in the hypothalamo-pituitary gonadal axis ?

    PubMed

    Rak, Agnieszka; Mellouk, Namya; Froment, Pascal; Dupont, Joëlle

    2017-03-22

    Adipokines, including adiponectin and resistin, are cytokines produced mainly by adipose tissue. They play a significant role in the metabolic functions that regulate insulin sensitivity and inflammation. Alteration of adiponectin and resistin plasma levels, or their expression in metabolic and gonadal tissue, are observed in some metabolic pathologies, such as obesity. Several studies have shown that these two hormones and the receptors for adiponectin, AdipoR1 and AdipoR2, are present in various reproductive tissues in both sexes of different species. Thus, these adipokines could be metabolic signals that partially explain infertility related to obesity, such as polycystic ovary syndrome (PCOS). Species and gender differences in plasma levels, tissue or cell distribution and hormonal regulation have been reported for resistin and adiponectin. Furthermore, until now, it has been unclear whether adiponectin and resistin act directly or indirectly on the hypothalamo-pituitary-gonadal axis. The objective of this review was to summarize the latest findings and particularly the species and gender differences known to date of adiponectin and resistin on female and male reproduction, based on the hypothalamo-pituitary-gonadal axis.

  20. Changes in Serum Adiponectin in Mice Chronically Exposed to Inorganic Arsenic in Drinking Water.

    PubMed

    Song, Xuanbo; Li, Ying; Liu, Junqiu; Ji, Xiaohong; Zhao, Lijun; Wei, Yudan

    2017-02-11

    Cardiovascular disease and diabetes mellitus are prominent features of glucose and lipid metabolism disorders. Adiponectin is a key adipokine that is largely involved in glucose and lipid metabolism processes. A growing body of evidence suggests that chronic exposure to inorganic arsenic is associated with cardiovascular disease and diabetes mellitus. We hypothesized that arsenic exposure may increase the risk of cardiovascular disease and diabetes mellitus by affecting the level of adiponectin. In this study, we examined serum adiponectin levels, as well as serum levels of metabolic measures (including fasting blood glucose, insulin, total cholesterol, triglyceride, and high-density lipoprotein (HDL)-cholesterol) in C57BL/6 mice exposed to inorganic arsenic in drinking water (5 and 50 ppm NaAsO2) for 18 weeks. Body mass and adiposity were monitored throughout the study. We found no significant changes in serum insulin and glucose levels in mice treated with arsenic for 18 weeks. However, arsenic exposure decreased serum levels of adiponectin, triglyceride, and HDL-cholesterol. Further, an inverse relationship was observed between urinary concentrations of total arsenic and serum levels of adiponectin. This study suggests that arsenic exposure could disturb the metabolism of lipids and increase the risk of cardiovascular disease by reducing the level of adiponectin.

  1. [Adiponectin, insulin and glucose concentrations in overweight and obese subjects after a complex carbohydrates (fiber) diet].

    PubMed

    González Rodríguez, Dora Cristina; Solano R, Liseti; González Martínez, Julio César

    2009-09-01

    Adiponectin one of the cytokines secreted by the adipose tissue that regulates the energetic metabolism through glucose and insulin interactions, stimulates the oxidation of fatty acids, reduces the plasmatic triglycerides and improves glucose metabolism by increasing insulin sensibility. Serum concentrations of adiponectin, insulin and glucose were assessed in order to establish association to weight loss after a dietary regime based on consumption of complex carbohydrates (fiber) during six weeks. Overweight and obese subjects (n=56) were studied by anthropometry. Adiponectin and insulin were measured by ELISA and glucose by Colorimetry. Data was analyzed by non parametric tests to compare independent or related samples. 12 men and 44 women, aged 20 to 55 years, 17 overweight and 39 obese were assessed. Adiponectin concentration was significantly low at basal determination in all the subjects (4,47 +/- 1,64); being higher in women (4,62 +/- 1,57 vs 3,93 +/- 1,86 microU/mL in men), while glucose and insulin values were at normal range (82,46 +/-26,51 mg/dL and 14,12 +/- 10,15 microU/mL) respectively with no significant differences for sex. Overweight subjects had significantly higher adiponectin concentrations than obese participants, at all measurements. Dietary regime promoted significant increase in adiponectin concentration at second and sixth week, with a negative correlation to body mass index and gender as they lost body weight.

  2. The Relationship between Maternal Plasma Leptin and Adiponectin Concentrations and Newborn Adiposity

    PubMed Central

    Castro, Natália P.; Euclydes, Verônica V.; Simões, Fernanda A.; Vaz-de-Lima, Lourdes R. A.; De Brito, Cyro A.; Luzia, Liania A.; Devakumar, Delan; Rondó, Patrícia H. C.

    2017-01-01

    Increased maternal blood concentrations of leptin and decreased adiponectin levels, which are common disturbances in obesity, may be involved in offspring adiposity by programming fetal adipose tissue development. The aim of this study was to assess the relationship between maternal leptin and adiponectin concentrations and newborn adiposity. This was a cross-sectional study involving 210 healthy mother-newborn pairs from a public maternity hospital in São Paulo, Brazil. Maternal blood samples were collected after delivery and leptin and adiponectin concentrations were measured by enzyme-linked immunosorbent assay. Newborn body composition was estimated by air displacement plethysmography. The association between maternal leptin and adiponectin concentrations and newborn adiposity (fat mass percentage, FM%) was evaluated by multiple linear regression, controlling for maternal age, socioeconomic status, parity, pre-pregnancy body mass index (BMI), weight gain, gestational age, and newborn age at the time of measurement. No relationship was found between maternal leptin and FM% of male or female newborn infants. Maternal adiponectin (p = 0.001) and pre-pregnancy BMI (p < 0.001; adj. R2 = 0.19) were positively associated with FM% of newborn males, indicating that maternal adiponectin is involved in fetal fat deposition in a sex-specific manner. Large-scale epidemiological, longitudinal studies are necessary to confirm our results. PMID:28241462

  3. Effects of pasteurization on adiponectin and insulin concentrations in donor human milk.

    PubMed

    Ley, Sylvia H; Hanley, Anthony J; Stone, Debbie; O'Connor, Deborah L

    2011-09-01

    Although pasteurization is recommended before distributing donor human milk in North America, limited data are available on its impact on metabolic hormones in milk. We aimed to investigate the effects of pasteurization on adiponectin and insulin concentrations in donor human milk. The study investigates concentrations of components in donor human milk before and after Holder pasteurization. After the guidelines of the Human Milk Bank Association of North America, human milk samples were pooled to produce 17 distinct batches (4 individuals per batch) and pasteurized at 62.5°C for 30 min. Adiponectin, insulin, energy, fat, total protein, and glucose concentrations were measured pre- and postpasteurization. Pasteurization reduced milk adiponectin and insulin by 32.8 and 46.1%, respectively (both p < 0.0001). Adiponectin and insulin were significantly correlated with energy and fat milk composition (r = 0.36-0.47; all p < 0.05). Pasteurization effects on milk hormone concentrations remained significant after adjusting for fat and energy (beta ± SEE: -4.11 ± 1.27, p = 0.003 for adiponectin; -70.0 ± 15.0, p < 0.0001 for insulin). Holder pasteurization reduced adiponectin and insulin concentrations in donor human milk. In view of emerging knowledge on the importance of milk components, continued work to find the optimal pasteurization process that mitigates risks but promotes retention of bioactive components is needed.

  4. The effects of adiponectin and leptin on human endothelial cell proliferation: a live-cell study.

    PubMed

    Alvarez, Granada; Visitación Bartolomé, M; Miana, María; Jurado-López, Raquel; Martín, Ruben; Zuluaga, Pilar; Martinez-Martinez, Ernesto; Nieto, M Luisa; Alvarez-Sala, Luis A; Millán, Jesús; Lahera, Vicente; Cachofeiro, Victoria

    2012-01-01

    The effect of adiponectin and leptin on the proliferation of the human microvascular endothelial cell line (HMEC-1) was studied in the absence or presence of fetal bovine serum (FBS). The participation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI-3K/Akt) pathways in this effect were evaluated. We studied the effect of both adipokines on the motility, mitosis, proliferation and cell death processes of HMEC-1 cells using live-cell imaging techniques. Adiponectin but not leptin further increased the proliferative effect induced by FBS on HMEC-1. This effect seems to be the consequence of an increase in the mitotic index in adiponectin-treated cells when compared to untreated ones. The presence of either the mitogen-activated protein kinase (MAPK) inhibitor (PD98059), or PI-3K inhibitor (LY294002), reduced the effect of adiponectin in a dose-dependent manner. Neither adipokine was able to affect HMEC-1 proliferation in FBS-free conditions. Duration of mitosis, cell motility and the cell death process were similar in all conditions. These data suggest that adiponectin and leptin exert different effects on endothelial cell function. Adiponectin was able to potentiate proliferation of HMEC-1. This effect involves the activation of both PI3-K/Akt and ERK/MAPK pathways. However, it seems to exert minimal effects on HMEC-1 function in the case of leptin.

  5. Adiponectin concentrations increase during acute FFA elevation in humans treated with rosiglitazone.

    PubMed

    Krzyzanowska, K; Mittermayer, F; Krugluger, W; Roden, M; Schernthaner, G; Wolzt, M

    2007-10-01

    The adipocytokine adiponectin is released by adipocytes upon activation of the peroxisome proliferator-activated receptor gamma (PPAR gamma). PPAR gamma has binding sites for thiazolidinediones and free fatty acids (FFAs). To evaluate if adiponectin serum concentrations are synergistically regulated by FFAs and thiazolidinediones IN VIVO plasma FFAs were acutely elevated in healthy subjects pre-treated with rosiglitazone or placebo. Sixteen healthy male subjects (23-37 years) were included in this double-blind, randomized, placebo-controlled parallel-group study. Rosiglitazone 8 mg or placebo was administered daily for 21 days. On the last day plasma FFA concentrations were increased by an intravenous triglyceride/heparin infusion. Blood for determination of adiponectin, C-reactive protein (CRP), leptin, resistin, FFAs, glucose, and insulin was drawn at baseline and on day 21 before and after 5 hours of triglyceride/heparin infusion. Adiponectin concentrations increased and FFA levels decreased in subjects receiving rosiglitazone (all p<0.05 VS. baseline). Lipid infusion significantly increased FFA plasma concentrations, with an attenuated elevation in rosiglitazone-treated subjects. However, adiponectin concentrations were only increased in subjects on rosiglitazone (p=0.018 VS. before lipid infusion), but not in controls. Leptin increased during lipid infusion in subjects receiving placebo but not in those on rosiglitazone. CRP and resistin were not affected by rosiglitazone or FFAs. The acute increase in circulating adiponectin concentrations during acutely elevated FFA depends on PPAR gamma activation in healthy subjects.

  6. Adiponectin Suppresses UVB-Induced Premature Senescence and hBD2 Overexpression in Human Keratinocytes

    PubMed Central

    Kim, MinJeong; Park, Kui Young; Lee, Mi-Kyung; Jin, Taewon; Seo, Seong Jun

    2016-01-01

    Recent studies have revealed that adiponectin can suppress cellular inflammatory signaling pathways. This study aimed to elucidate the effect of adiponectin on the unregulated production of hBD2 in UVB-induced premature senescent keratinocytes. We constructed an in vitro model of premature senescent keratinocytes through repeated exposure to low energy UVB. After repeated low energy UVB exposure, there was significant generation of reactive oxygen species (ROS) and induction of senescence-associated markers, including senescence associated beta-galactosidase activity and expression of p16INK4a and histone H2AX. In addition, the present clinical study showed higher expression of hBD2 in sun-exposed skin of elderly group, and the overexpression of hBD2 was observed by c-Fos activation in vitro. Adiponectin has the ability to scavenge ROS and consequently inhibit MAPKs and SA-markers in UVB-exposed keratinocytes. An inhibitor study demonstrated that adiponectin downregulated hBD2 mRNA expression through suppression of the AP-1 transcription factor components c-Fos via inactivation of p38 MAPK. Collectively, the dysregulated production of hBD2 by the induction of oxidative stress was attenuated by adiponectin through the suppression of p38 and JNK/SAPK MAPK signaling in UVB-mediated premature senescent inducible conditions. These results suggest the feasibility of adiponectin as an anti-photoaging and anti-inflammatory agent in the skin. PMID:27526049

  7. Increased beta -oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin.

    PubMed

    Ma, Ke; Cabrero, Agatha; Saha, Pradip K; Kojima, Hideto; Li, Lan; Chang, Benny Hung-Junn; Paul, Antoni; Chan, Lawrence

    2002-09-20

    Previous reports showed that recombinant fragments of adiponectin (adipo) displayed pharmacological effects when injected into rodents, but the relevance of these observations to the physiological function of adipo is unclear. We generated Adipo(-/-) mice by gene targeting. Adipo(-/-) mice are fertile with normal body and fat pad weights. Plasma glucose and insulin levels of Adipo(-/-) and Adipo(+/+) mice are similar under fasting conditions and during an intraperitoneal glucose tolerance test (GTT). Insulin tolerance test (ITT) also produces similar plasma glucose and insulin levels in the two groups of mice. Hyperinsulinemic-euglycemic clamp analysis showed that Adipo(-/-) and Adipo(+/+) mice have similar glucose infusion rates to maintain a similar serum glucose. High-fat diet feeding for 7 months led to similar weight gain and similar GTT and ITT responses. We next measured beta-oxidation and found it to be significantly increased in muscle and liver of Adipo(-/-) mice. In conclusion, our study indicates that absence of adipo causes increased beta-oxidation but does not cause glucose intolerance or insulin resistance in mice.

  8. Succination of thiol groups in adipose tissue proteins in diabetes: succination inhibits polymerization and secretion of adiponectin.

    PubMed

    Frizzell, Norma; Rajesh, Mathur; Jepson, Matthew J; Nagai, Ryoji; Carson, James A; Thorpe, Suzanne R; Baynes, John W

    2009-09-18

    S-(2-Succinyl)cysteine (2SC) is formed by reaction of the Krebs cycle intermediate fumarate with cysteine residues in protein, a process termed succination of protein. Both fumarate and succination of proteins are increased in adipocytes cultured in high glucose medium (Nagai, R., Brock, J. W., Blatnik, M., Baatz, J. E., Bethard, J., Walla, M. D., Thorpe, S. R., Baynes, J. W., and Frizzell, N. (2007) J. Biol. Chem. 282, 34219-34228). We show here that succination of protein is also increased in epididymal, mesenteric, and subcutaneous adipose tissue of diabetic (db/db) mice and that adiponectin is a major target for succination in both adipocytes and adipose tissue. Cys-39, which is involved in cross-linking of adiponectin monomers to form trimers, was identified as a key site of succination of adiponectin in adipocytes. 2SC was detected on two of seven monomeric forms of adiponectin immunoprecipitated from adipocytes and epididymal adipose tissue. Based on densitometry, 2SC-adiponectin accounted for approximately 7 and 8% of total intracellular adiponectin in cells and tissue, respectively. 2SC was found only in the intracellular, monomeric forms of adiponectin and was not detectable in polymeric forms of adiponectin in cell culture medium or plasma. We conclude that succination of adiponectin blocks its incorporation into trimeric and higher molecular weight, secreted forms of adiponectin. We propose that succination of proteins is a biomarker of mitochondrial stress and accumulation of Krebs cycle intermediates in adipose tissue in diabetes and that succination of adiponectin may contribute to the decrease in plasma adiponectin in diabetes.

  9. Effects of Adiponectin Including Reduction of Androstenedione Secretion and Ovarian Oxidative Stress Parameters In Vivo

    PubMed Central

    Comim, Fabio V.; Gutierrez, Karina; Bridi, Alessandra; Bochi, Guilherme; Chemeris, Raisa; Rigo, Melânia L.; Dau, Andressa Minussi P.; Cezar, Alfredo S.; Moresco, Rafael Noal; Gonçalves, Paulo Bayard Dias

    2016-01-01

    Adiponectin is the most abundantly produced human adipokine with anti-inflammatory, anti-oxidative, and insulin-sensitizing properties. Evidence from in vitro studies has indicated that adiponectin has a potential role in reproduction because it reduces the production of androstenedione in bovine theca cells in vitro. However, this effect on androgen production has not yet been observed in vivo. The current study evaluated the effect of adiponectin on androstenedione secretion and oxidative stress parameters in a rodent model. Seven-week-old female Balb/c mice (n = 33), previously treated with equine gonadotropin chorionic, were assigned to one of four different treatments: Group 1, control (phosphate-buffered saline); Group 2, adiponectin 0.1 μg/mL; Group 3, adiponectin 1.0 μg/mL; Group 4, adiponectin 5.0 μg/mL. After 24 h, all animals were euthanized and androstenedione levels were measured in the serum while oxidative stress markers were quantified in whole ovary tissue. Female mice treated with adiponectin exhibited a significant reduction (about 60%) in serum androstenedione levels in comparison to controls. Androstenedione levels decreased from 0.78 ± 0.4 ng/mL (mean ± SD) in controls to 0.28 ± 0.06 ng/mL after adiponectin (5 μg/mL) treatment (P = 0.01). This change in androgen secretion after 24 hours of treatment was associated with a significant reduction in the expression of CYP11A1 and STAR (but not CYP17A1). In addition, ovarian AOPP product levels, a direct product of protein oxidation, decreased significantly in adiponectin-treated mice (5 μg/mL); AOPP (mean ± SD) decreased to 4.3 ± 2.1 μmol/L in comparison with that of the controls (11.5 ± 1.7 μmol/L; P = 0.0003). Our results demonstrated for the first time that acute treatment with adiponectin reduced the levels of a direct oxidative stress marker in the ovary as well as decreased androstenedione serum levels in vivo after 24 h. PMID:27158926

  10. Evaluation of Serum Adiponectin Concentrations Among Drug Abusers on Methadone Maintenance Treatment

    PubMed Central

    Montazerifar, Farzaneh; Karajibani, Mansour; Lashkaripour, Kobra; Yousefi, Maryam

    2013-01-01

    Background: Adiponectin, an adipocyte-derived protein, modulates a number of metabolic processes. Methadone maintenance treatment (MMT) changes the level of hormones produced by adipose tissue in addicts. However, current data remains contradictory. Objectives: The aim of this study was to evaluate the effect of MMT on serum adiponectin levels in drug addicts. Materials and Methods: Twenty-five drug abusers with a mean age of 37.4 ± 8.7 years were referred to the Baharan Hospital, Zahedan, and 22 healthy age-matched control subjects with a mean age of 35 ± 9.5 years were enrolled in the study. Addicts were treated with methadone at (40 to 120 mg/d) for six months. Measurement of anthropometric parameters, serum adiponectin, and biochemical parameter levels, were assessed in the addicts, before and after six months of MMT, but only once in the healthy controls. Results: The mean basal serum adiponectin level was not significantly lower in the drug abuser group compared to the healthy subjects (P > 0.05). After six months of MMT, the mean serum adiponectin level of the drug addicts was not significantly different from their mean baseline level or that of the healthy subjects (P > 0.05). However, the mean baseline serum adiponectin level was significantly lower in overweight/obese addicts when compared to underweight patients and healthy individuals (P < 0.001). After six months of MMT, the mean level of serum adiponectin increased significantly in the underweight subjects compared to the normal weight and overweight/obese subjects (P < 0.0001) and the control group (P < 0.001). Adiponectin concentration was correlated inversely with body mass index and positively correlated with waist circumference and serum high-density lipoprotein levels. Conclusions: This study showed that MMT did not markedly alter the concentration of serum adiponectin in drug abusers. However, in regard to the variations in the serum lipid profiles and anthropometric parameters, the findings

  11. CRP and adiponectin and its oligomers in the metabolic syndrome: evaluation of new laboratory-based biomarkers.

    PubMed

    Devaraj, Sridevi; Swarbrick, Michael M; Singh, Uma; Adams-Huet, Beverley; Havel, Peter J; Jialal, Ishwarlal

    2008-05-01

    The metabolic syndrome (MetS) confers an increased risk for diabetes and cardiovascular disease. Although high-sensitive C-reactive protein (hsCRP) concentrations are higher and adiponectin concentrations lower in MetS, there is no reliable biochemical measure that can capture its various features. We evaluated whether hsCRP, adiponectin, or the ratio of adiponectin or its oligomers, especially the high-molecular-weight (HMW) oligomer, to hsCRP predict MetS in 123 subjects with MetS compared with that in 91 healthy control subjects. MetS subjects had significantly higher hsCRP levels and lower total adiponectin and oligomer levels relative to control subjects (P < .0001). The HMW/total adiponectin and adiponectin/CRP ratios were significantly lower in MetS subjects than control subjects (P < .005). The odds ratio (OR) of MetS using the 75th percentile cutoff for CRP was 3.8 (95% confidence interval [CI], 2.1-6.8) and equivalent to low total adiponectin (OR, 2.5; 95% CI, 1.3-4.5), its oligomers, or the adiponectin/ hsCRP ratio (OR, 2.6; 95% CI, 1.5, 4.8). Thus, measurements of CRP, adiponectin, or its oligomers provide robust biomarkers for predicting MetS.

  12. Adiponectin reduces ER stress-induced apoptosis through PPARα transcriptional regulation of ATF2 in mouse adipose

    PubMed Central

    Liu, Zhenjiang; Gan, Lu; Wu, Tianjiao; Feng, Fei; Luo, Dan; Gu, Huihui; Liu, Shimin; Sun, Chao

    2016-01-01

    Adiponectin is a cytokine produced predominantly by adipose tissue and correlates with glucose and lipid homeostasis. However, the effects of adiponectin on endoplasmic reticulum (ER) stress and apoptosis of adipose tissue remain elusive. In this study, we found that tunicamycin-induced ER stress increased serum free fatty acid (FFA) and impaired glucose tolerance, elevated the mRNA levels of GRP78, Chop, ATF2 and caspase 3, but reduced adiponectin mRNA level in white adipose tissue. Moreover, ER stress-triggered adipocyte apoptosis by increasing cellular FFA level and Ca2+ level. Further analysis revealed that adiponectin alleviated ER stress-induced adipocyte apoptosis by elevating peroxisome proliferator-activated receptor alpha (PPARα) mRNA level. Our data also confirmed that adiponectin reduced early apoptotic cells and blocked the mitochondrial apoptosis pathway by activating the AdipoR1/AMP-activated protein kinase (AMPK) signal pathway. In addition, PPARα bound to ATF2 promoter region and inhibited transcription of ATF2. The inhibition of adipocyte apoptosis by adiponectin was correlated with transcriptional suppression of ATF2. Furthermore, adiponectin inhibited ER stress-induced apoptosis by activating the AMPK/PKC pathway. In summary, our data demonstrate adiponectin inhibited ER stress and apoptosis of adipocyte in vivo and in vitro by activating the AMPK/PPARα/ATF2 pathway. Our study establishes that adiponectin is an important adipocytokine for preventing and treating obesity. PMID:27882945

  13. Adiponectin complexes composition in Japanese-Brazilians regarding their glucose tolerance status

    PubMed Central

    2013-01-01

    Background Adiponectin circulates in different multimer complexes comprised of low molecular weight trimeric form (LMW), hexamer of middle molecular weight (MMW) and high molecular weight multimers (HMW). In Japanese-Brazilians, a population with high prevalence of glucose metabolism disturbances, we examined the associations of total adiponectin and its multimers with diabetes mellitus. Methods Two study groups were examined: 26 patients with diabetes mellitus (DM,14 women and 12 men, aged 55.3 ± 8.6 years) and 27 age-matched control subjects with normal glucose tolerance (NGT,12 women and 15 men, aged 54.0 ± 9.2 years). Results We found no significant differences in total [NGT: 6.90 ug/ml (4.38-13.43); DM: 5.38 ug/ml (3.76-8.56), p = 0.35], MMW [NGT:2.34 ug/ml (1.38-3.25); DM: 1.80 ug/ml (1.18-2.84), p = 0.48] or LMW adiponectin [NGT: 2.07 ug/ml (1.45-3.48), DM: 2.93 ug/ml (1.78-3.99), p = 0.32] between groups. In contrast, HMW adiponectin levels were significantly lower in patients with DM [TGN: 2.39 ug/ml (1.20-4.75); DM: 1.04 ug/ml (0.42-1.60), p = 0.001]. A logistic regression analysis was done to identify independent associations with diabetes mellitus. The results showed that HOMA-IR and HMW adiponectin in women were independently associated with diabetes mellitus. Conclusion The current investigation demonstrates that in Japanese-Brazilians HMW adiponectin is selectively reduced in individuals with type 2 diabetes, while no differences were found in MMW and LMW adiponectin isoforms. PMID:23570346

  14. Associations of Insulin Resistance and Adiponectin With Mortality in Women With Breast Cancer

    PubMed Central

    Duggan, Catherine; Irwin, Melinda L.; Xiao, Liren; Henderson, Katherine D.; Smith, Ashley Wilder; Baumgartner, Richard N.; Baumgartner, Kathy B.; Bernstein, Leslie; Ballard-Barbash, Rachel; McTiernan, Anne

    2011-01-01

    Purpose Overweight or obese breast cancer patients have a worse prognosis compared with normal-weight patients. This may be attributed to hyperinsulinemia and dysregulation of adipokine levels associated with overweight and obesity. Here, we evaluate whether low levels of adiponectin and a greater level of insulin resistance are associated with breast cancer mortality and all-cause mortality. Patients and Methods We measured glucose, insulin, and adiponectin levels in fasting serum samples from 527 women enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between adiponectin and insulin and glucose levels (expressed as the Homeostatic Model Assessment [HOMA] score) represented as continuous measures and median split categories, along with breast cancer mortality and all-cause mortality, using Cox proportional hazards models. Results Increasing HOMA scores were associated with reduced breast cancer survival (hazard ratio [HR], 1.12; 95% CI, 1.05 to 1.20) and reduced all-cause survival (HR, 1.09; 95% CI, 1.02 to 1.15) after adjustment for possible confounders. Higher levels of adiponectin (above the median: 15.5 μg/mL) were associated with longer breast cancer survival (HR, 0.39; 95% CI, 0.15 to 0.95) after adjustment for covariates. A continuous measure of adiponectin was not associated with either breast cancer–specific or all-cause mortality. Conclusion Elevated HOMA scores and low levels of adiponectin, both associated with obesity, were associated with increased breast cancer mortality. To the best of our knowledge, this is the first demonstration of the association between low levels of adiponectin and increased breast cancer mortality in breast cancer survivors. PMID:21115858

  15. Circulating adiponectin levels in various malignancies: an updated meta-analysis of 107 studies

    PubMed Central

    Peng, Xin; Wu, Li-Ling; Yu, Guang-Yan

    2016-01-01

    Early detection of cancers is challenging for lack of specific biomarkers. Adiponectin is an adipokine predominantly derived from adipocytes and hypoadiponectinemia has been reported to associate with risk of many types of cancers. However, available evidence is controversial. Some studies show that increased adiponectin levels correlate with cancer risk. Therefore, we performed a meta-analysis of the association between circulating adiponectin levels and cancer development. A systematic search of PubMed, EMBASE, Wiley Online Library and Cochrane Library was conducted for eligible studies involving circulating adiponectin and malignancies from inception to August 8, 2015. Standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated by use of a random-effect model. Funnel plot and Egger's linear regression test were conducted to examine the risk of publication bias. 107 studies were included with 19,319 cases and 25,675 controls. The pooled analysis indicated that circulating adiponectin levels were lower in patients with various cancers than in controls, with a pooled SMD of −0.334 μg/ml (95% CI, −0.465 to −0.203, P = 0.000). No evidence of publication bias was observed. Circulating high molecular weight adiponectin levels were also lower in cancer patients than in controls, with a pooled SMD of −0.502 μg/ml (95% CI, −0.957 to −0.047, P = 0.000). This meta-analysis provides further evidence that decreased adiponectin levels is associated with risk of various cancers. Hypoadiponectinemia may represent a useful biomarker for early detection of cancers. PMID:27119501

  16. Circulating adiponectin levels in various malignancies: an updated meta-analysis of 107 studies.

    PubMed

    Wei, Tai; Ye, Peng; Peng, Xin; Wu, Li-Ling; Yu, Guang-Yan

    2016-07-26

    Early detection of cancers is challenging for lack of specific biomarkers. Adiponectin is an adipokine predominantly derived from adipocytes and hypoadiponectinemia has been reported to associate with risk of many types of cancers. However, available evidence is controversial. Some studies show that increased adiponectin levels correlate with cancer risk. Therefore, we performed a meta-analysis of the association between circulating adiponectin levels and cancer development. A systematic search of PubMed, EMBASE, Wiley Online Library and Cochrane Library was conducted for eligible studies involving circulating adiponectin and malignancies from inception to August 8, 2015. Standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated by use of a random-effect model. Funnel plot and Egger's linear regression test were conducted to examine the risk of publication bias. 107 studies were included with 19,319 cases and 25,675 controls. The pooled analysis indicated that circulating adiponectin levels were lower in patients with various cancers than in controls, with a pooled SMD of -0.334 μg/ml (95% CI, -0.465 to -0.203, P = 0.000). No evidence of publication bias was observed. Circulating high molecular weight adiponectin levels were also lower in cancer patients than in controls, with a pooled SMD of -0.502 μg/ml (95% CI, -0.957 to -0.047, P = 0.000). This meta-analysis provides further evidence that decreased adiponectin levels is associated with risk of various cancers. Hypoadiponectinemia may represent a useful biomarker for early detection of cancers.

  17. Adiponectin as a Protective Factor Against the Progression Toward Type 2 Diabetes Mellitus in Postmenopausal Women.

    PubMed

    Darabi, Hossein; Raeisi, Alireza; Kalantarhormozi, Mohammad Reza; Ostovar, Afshin; Assadi, Majid; Asadipooya, Kamyar; Vahdat, Katayoun; Dobaradaran, Sina; Nabipour, Iraj

    2015-08-01

    Serum adiponectin levels have been suggested to be predictors of type 2 diabetes mellitus in diverse populations. However, the relationship between circulating adiponectin levels and the risk of development of type 2 diabetes in postmenopausal women has not been investigated.A total of 382 healthy postmenopausal women who participated in a prospective cohort study were followed for 5.8 years. Type 2 diabetes mellitus was defined according to the criteria set out by the American Diabetes Association. Adiponectin, osteoprotegerin (OPG), and high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA.Of 195 women who did not have diabetes at baseline and who were reexamined in the second phase of the study for diabetic status, 35 subjects (17.9%) developed type 2 diabetes mellitus during the 5.8 years follow-up period. The women with type 2 diabetes had lower adiponectin levels than the healthy postmenopausal women. Multiple regression analysis showed that, after adjustments were made for age, cardiovascular risk factors, OPG, and hs-CRP levels, higher baseline adiponectin levels were associated with a lower relative risk (RR) of having type 2 (RR = 0.07, confidence interval [CI]: 0.01-0.66, P = 0.021).Higher baseline adiponectin levels functioned as a predictor of a lower risk of developing type 2 diabetes mellitus among postmenopausal women during a 5.8 years follow-up study. Therefore, it is suggested that elevated adiponectin levels may offer protection against the development of type 2 diabetes mellitus after the menopause.

  18. Adiponectin, Leptin and Objectively Measured Physical Activity in Adults: A Narrative Review

    PubMed Central

    Nurnazahiah, Ali; Lua, Pei Lin; Shahril, Mohd Razif

    2016-01-01

    The objective of this study was to compile and analyse existing scientific evidences reporting the effects of objectively measured physical activity on the levels of adiponectin and leptin. Articles related to the effects of objectively measured physical activity on the levels of adiponectin and leptin were searched from the Medline and PubMed databases. The search was limited to ‘objectively measured’ physical activity, and studies that did not objectively measure the physical activity were excluded. Only English articles were included in the search and review. A total of 18 articles encompassing 2,026 respondents met the inclusion criteria. The eligible articles included all forms of evidence (e.g., cross-sectional and intervention). Seventeen and 11 studies showed the effects of objectively measured physical activity on adiponectin and leptin, respectively. Five and four cross-sectional studies showed the effects of objectively measured physical activity on adiponectin and leptin, respectively. Two out of five studies showed a weak to moderate positive association between adiponectin and objectively measured physical activity, while three out of four studies showed a weak to moderate inverse association between leptin and objectively measured physical activity. For intervention studies, six out of 12 studies involving adiponectin and five out of seven studies involving leptin showed a significant effect between the proteins and objectively measured physical activity. However, a definitive conclusion could not be drawn due to several methodological flaws in the existing articles and the acute lack of additional research in this area. In conclusion, the existing evidences are encouraging but yet not compelling. Hence, further well-designed large trials are needed before the effectiveness of objectively measured physical activity in elevating adiponectin levels and in decreasing leptin levels could be strongly confirmed. PMID:28090175

  19. Critical Role of AMPK/FoxO3A Axis in Globular Adiponectin-Induced Cell Cycle Arrest and Apoptosis in Cancer Cells.

    PubMed

    Shrestha, Anup; Nepal, Saroj; Kim, Mi Jin; Chang, Jae Hoon; Kim, Sang-Hyun; Jeong, Gil-Saeng; Jeong, Chul-Ho; Park, Gyu Hwan; Jung, Sunghee; Lim, Jaecheong; Cho, Eunha; Lee, Soyoung; Park, Pil-Hoon

    2016-02-01

    Adiponectin predominantly secreted from adipose tissue has exhibited potent anti-proliferative properties in cancer cells via modulating cell cycle and apoptosis. FoxO3A, a Forkhead box O member of the transcription factor, plays a critical role in modulating expression of genes involved in cell death and/or survival. In this study, we investigated the role of FoxO3A signaling in anti-cancer activities of adiponectin. Herein, we have shown that treatment with globular adiponectin (gAcrp) increases p27 but decreases cyclinD1 expression in human hepatoma (HepG2) and breast (MCF-7) cancer cells. Gene ablation of FoxO3A prevented gAcrp-induced increase in p27 and decreased in cyclin D1 expression, and further ameliorated cell cycle arrest by gAcrp, indicating a critical role of FoxO3A in gAcrp-induced cell cycle arrest of cancer cells. Moreover, treatment with gAcrp also induced caspase-3/7 activation and increased Fas ligand (FasL) expression in both HepG2 and MCF-7 cells. Transfection with FoxO3A siRNA inhibited gAcrp-induced caspase-3/7 activation and FasL expression, suggesting that FoxO3A signaling also plays an important role in gAcrp-induced apoptosis of cancer cells. We also found that gene silencing of AMPK prevented gAcrp-induced nuclear translocation of FoxO3A in HepG2 and MCF-7 cells. In addition, suppression of AMPK also blocked gAcrp-induced cell cycle arrest and further attenuated gAcrp-induced caspase-3/7 activation, indicating that AMPK signaling plays a pivotal role in both gAcrp-induced cell cycle arrest and apoptosis via acting as an upstream signaling of FoxO3A. Taken together, our findings demonstrated that AMPK/FoxO3A axis plays a cardinal role in anti-proliferative effect of adiponectin in cancer cells.

  20. Adiponectin enhances osteogenic differentiation in human adipose-derived stem cells by activating the APPL1-AMPK signaling pathway

    SciTech Connect

    Chen, Tong; Wu, Yu-wei; Lu, Hui; Guo, Yuan; Tang, Zhi-hui

    2015-05-29

    Human adipose-derived stem cells (hASCs) are multipotent progenitor cells with multi-lineage differentiation potential including osteogenesis and adipogenesis. While significant progress has been made in understanding the transcriptional control of hASC fate, little is known about how hASC differentiation is regulated by the autocrine loop. The most abundant adipocytokine secreted by adipocytes, adiponectin (APN) plays a pivotal role in glucose metabolism and energy homeostasis. Growing evidence suggests a positive association between APN and bone formation yet little is known regarding the direct effects of APN on hASC osteogenesis. Therefore, this study was designed to investigate the varied osteogenic effects and regulatory mechanisms of APN in the osteogenic commitment of hASCs. We found that APN enhanced the expression of osteoblast-related genes in hASCs, such as osteocalcin, alkaline phosphatase, and runt-related transcription factor-2 (Runx2, also known as CBFa1), in a dose- and time-dependent manner. This was further confirmed by the higher expression levels of alkaline phosphatase and increased formation of mineralization nodules, along with the absence of inhibition of cell proliferation. Importantly, APN at 1 μg/ml was the optimal concentration, resulting in maximum deposition of calcium nodules, and was significant superior to bone morphogenetic protein 2. Mechanistically, we found for the first time that APN increased nuclear translocation of the leucine zipper motif (APPL)-1 as well as AMP-activated protein kinase (AMPK) phosphorylation, which were reversed by pretreatment with APPL1 siRNA. Our results indicate that APN promotes the osteogenic differentiation of hASCs by activating APPL1-AMPK signaling, suggesting that manipulation of APN is a novel therapeutic target for controlling hASC fate. - Highlights: • Adiponectin enhances osteogenic differentiation in human adipose-derived stem cells. • The knock-down of APPL1 block the enhancement of

  1. New targets to alleviate skeletal muscle inflammation: role of microRNAs regulated by adiponectin.

    PubMed

    Boursereau, Raphaël; Abou-Samra, Michel; Lecompte, Sophie; Noel, Laurence; Brichard, Sonia M

    2017-02-27

    Muscle inflammation worsens metabolic disorders as well as devastating myopathies. The hormone adiponectin (ApN) has emerged has a master regulator of inflammation/immunity in several tissues including the skeletal muscle. In this work, we explore whether microRNAs regulated by ApN may represent novel mechanisms for controlling muscle inflammation. By screening arrays, we found miR-711 as a strong candidate for mediating ApN action. Thus, ApN-knockout mice showed decreased muscular expression of miR-711 together with enhanced inflammation/oxidative stress markers, while mice overexpressing ApN showed increased miR-711 levels. Likewise, electrotransfer of the ApN gene in muscle of ApN-knockout mice upregulated miR-711 while reducing inflammation and oxidative stress. Similar data were obtained in murine C2C12 cells or in human primary myotubes treated with ApN. MiR-711 overexpression downregulated several components of the Toll-like receptor-4 (TLR4) pathway, which led to repression of NF-κB activity and downstream pro-inflammatory cytokines. MiR-711 blockade had opposite effects. Moreover, muscle electrotransfer of pre-miR-711 recapitulated in vivo the anti-inflammatory effects observed in vitro. Thus, miR-711, which is upregulated by ApN represses TLR4 signaling, acting therefore as a major mediator of the anti-inflammatory action of ApN. This novel miRNA and its related target genes may open new therapeutic perspectives for controlling muscle inflammation.

  2. New targets to alleviate skeletal muscle inflammation: role of microRNAs regulated by adiponectin

    PubMed Central

    Boursereau, Raphaël; Abou-Samra, Michel; Lecompte, Sophie; Noel, Laurence; Brichard, Sonia M.

    2017-01-01

    Muscle inflammation worsens metabolic disorders as well as devastating myopathies. The hormone adiponectin (ApN) has emerged has a master regulator of inflammation/immunity in several tissues including the skeletal muscle. In this work, we explore whether microRNAs regulated by ApN may represent novel mechanisms for controlling muscle inflammation. By screening arrays, we found miR-711 as a strong candidate for mediating ApN action. Thus, ApN-knockout mice showed decreased muscular expression of miR-711 together with enhanced inflammation/oxidative stress markers, while mice overexpressing ApN showed increased miR-711 levels. Likewise, electrotransfer of the ApN gene in muscle of ApN-knockout mice upregulated miR-711 while reducing inflammation and oxidative stress. Similar data were obtained in murine C2C12 cells or in human primary myotubes treated with ApN. MiR-711 overexpression downregulated several components of the Toll-like receptor-4 (TLR4) pathway, which led to repression of NF-κB activity and downstream pro-inflammatory cytokines. MiR-711 blockade had opposite effects. Moreover, muscle electrotransfer of pre-miR-711 recapitulated in vivo the anti-inflammatory effects observed in vitro. Thus, miR-711, which is upregulated by ApN represses TLR4 signaling, acting therefore as a major mediator of the anti-inflammatory action of ApN. This novel miRNA and its related target genes may open new therapeutic perspectives for controlling muscle inflammation. PMID:28240307

  3. Portal vein and systemic adiponectin concentrations are closely linked with hepatic glucose and lipoprotein kinetics in extremely obese subjects.

    PubMed

    Magkos, Faidon; Fabbrini, Elisa; Patterson, Bruce W; Eagon, J Christopher; Klein, Samuel

    2011-11-01

    Low systemic plasma adiponectin concentrations are associated with abnormalities in hepatic glucose and lipoprotein metabolism in obese people. However, the relationship between the delivery of adiponectin to the liver via the portal vein and hepatic glucose and lipoprotein metabolism is not known. We examined the relationship between hepatic substrate metabolism (glucose rate of appearance into plasma and hepatic very low-density lipoprotein [VLDL]-triglyceride [TG] and VLDL-apolipoprotein B-100 [apoB-100] secretion rates, determined by using stable isotope-labeled tracer techniques) and portal vein adiponectin concentration, in 8 insulin-resistant, extremely obese subjects (body mass index, 65 ± 7 kg/m(2)). Portal vein adiponectin concentration was inversely associated with basal glucose rate of appearance (r = -0.820, P = .013) and VLDL-TG (r = -0.823, P = .012) and VLDL-apoB-100 (r = -0.787, P = .020) secretion rates. Very similar correlations were obtained for radial artery adiponectin as a result of a mirroring relationship between portal and arterial adiponectin concentrations (r = 0.899, P = .002) and the absence of significant arteriovenous concentration differences (P = .570). Insulin resistance, assessed with the homeostasis model assessment score, was also strongly associated with hepatic glucose and lipid metabolic parameters, as well as with adiponectin concentrations in the portal vein and radial artery. These results suggest that adiponectin delivery to the liver, whether via the portal or the systemic circulation, may be an important regulator of basal hepatic glucose, VLDL-TG, and VLDL-apoB-100 production rates in obese people, possibly through direct effects on the liver or changes in hepatic insulin sensitivity. However, portal vein adiponectin does not appear to be superior to arterial adiponectin as a marker of hepatic metabolic dysregulation. Additional studies are needed to elucidate the mechanism(s) responsible for the strong association

  4. The role of adiponectin in human vascular physiology.

    PubMed

    Vaiopoulos, Aristeidis G; Marinou, Kyriakoula; Christodoulides, Constantinos; Koutsilieris, Michael

    2012-03-08

    Adiponectin (ApN) is an adipose tissue-derived hormone which is involved in a wide variety of physiological processes including energy metabolism, inflammation, and vascular physiology via actions on a broad spectrum of target organs including liver, skeletal muscle, and vascular endothelium. Besides possessing insulin sensitizing and anti-inflammatory properties ApN also exerts a pivotal role in vascular protection through activation of multiple intracellular signaling cascades. Enhancement of nitric oxide generation and attenuation of reactive oxygen species production in endothelial cells along with reduced vascular smooth muscle cell proliferation and migration constitute some of ApN's vasoprotective actions. Additionally, recent data indicate that ApN has direct myocardio-protective effects. Decreased plasma ApN levels are implicated in the pathogenesis of the metabolic syndrome and atherosclerosis and may serve as a diagnostic and prognostic biomarker as well as a rational pharmaco-therapeutic target to treat these disorders. This review article summarizes recent work on the cardiovascular actions of ApN.

  5. Cardioprotection of ischemic preconditioning in rats involves upregulating adiponectin.

    PubMed

    Wang, Hui; Wu, Wenjing; Duan, Jun; Ma, Ming; Kong, Wei; Ke, Yuannan; Li, Gang; Zheng, Jingang

    2017-02-20

    It has been reported that ischemic preconditioning (IPC) and adiponectin (APN) are cardioprotective in many cardiovascular disorders. However, whether APN mediates the effect of IPC on myocardial injury has not been elucidated. This study was conducted to investigate whether IPC affects myocardial ischemic injury by increasing APN expression. Male adult rats with cardiac knockdowns of APN and its receptors via intramyocardial small-interfering RNA injection were subjected to IPC and then myocardial infarction (MI) at 24 h post-IPC. Globular APN (gAd) was injected at 10 min before MI. APN mRNA and protein levels in myocardium as well as the plasma APN concentration were markedly high at 6 and 12 h after IPC. IPC ameliorated myocardial injury as evidenced by improved cardiac functions and a reduced infarct size. Compared with the control MI group, rats in the IPC + MI group had elevated levels of left ventricular ejection fraction and fractional shortening, and a smaller MI size (P<0.05). However, the aforementioned protective effects were ameliorated in the absence of APN and APN receptors, followed by inhibition of AMP-activated protein kinase (AMPK) phosphorylation, but reversed by gAd treatment in wild-type rats, and AMPK phosphorylation increased (P<0.05). Overall, our results suggest that the cardioprotective effects of IPC are partially due to upregulation of APN, and provide a further insight into IPC-mediated signaling effects.

  6. Cord blood resistin and adiponectin in term newborns of diabetic mothers

    PubMed Central

    Mohamed, Maha H.; Gad, Ghada I.; Ibrahim, Hala Y.; El Shemi, Mohamed S.; Atef, Shereen H.; Ramadan, Naglaa M.; El Saeid, Shimaa M.

    2010-01-01

    Introduction Adipose tissue can release hormones into the blood stream in response to specific extracellular stimuli or changes in metabolic status. Resistin, an adipose-secreted factor, is primarily involved in the modulation of insulin sensitivity and adipocyte differentiation. Adiponectin, an adipocyte-specific hormone with insulin sensitizing, anti-inflammatory and anti-atherogenic effects, is reduced in obesity and type II diabetes. The aim of the study was to assess the influence of maternal pre-existing diabetes on cord blood resistin and adiponectin at birth in relation to neonatal anthropometric parameters and cord blood insulin levels. Material and methods A total of 60 term newborns were prospectively enrolled and categorized into three groups: 20 were macrosomic infants of pre-gestational diabetic mothers (group I), 20 were non-macrosomic infants of pre-gestational diabetic mothers (group II) and 20 were healthy non-macrosomic infants born to non-diabetic mothers serving as controls (group III). Infants’ anthropometric indices were recorded. Cord blood samples for glucose, insulin, resistin and adiponectin assay, together with maternal glycosylated haemoglobin were obtained. Results Serum insulin was increased while resistin and adiponectin were significantly decreased in infants of diabetic mothers (IDMs) compared to the control group. Serum glucose, insulin, resistin and adiponectin were comparable in group I and II. Cord serum resistin correlated positively with cord blood glucose in IDMs in both macrosomic and non-macrosomic groups. Cord serum insulin correlated positively with triceps skinfold thickness in all studied neonates. Cord serum resistin and adiponectin showed no correlation with neonatal anthropometric indices. Multiple regression analysis demonstrated that insulin, resistin and adiponectin together were highly correlated with birth weight, with adiponectin as the one responsible for this positive correlation. Conclusions Infants of

  7. Plasma Adiponectin Concentration and Its Association with Metabolic Syndrome in Patients with Heart Failure

    PubMed Central

    Won, Hoyoun; Shin, Min-Jeong; Oh, Jaewon; Hong, Namki; Park, Sungha; Lee, Sang-Hak; Jang, Yangsoo; Chung, Namsik

    2012-01-01

    Purpose Plasma adiponectin concentrations are inversely related with metabolic syndrome (MetS), and MetS is associated with increased risk for heart failure (HF). However, the relationship between adiponectin and MetS in HF remains undetermined. Therefore, we tested whether MetS was associated with the degree of plasma adiponectin concentrations in HF patients. Materials and Methods One hundred twenty eight ambulatory HF patients with left ventricular ejection fraction of <50% (80 males, 61.8±11.9 years old) were enrolled for this cross-sectional study. Echocardiographic measurements were performed, and plasma concentrations of adiponectin, lipoproteins, apolipoproteins (apoB, apoA1) and high sensitive C-reactive protein (hsCRP) were measured. Results Adiponectin concentrations in HF patients with MetS (n=43) were significantly lower than those without MetS (n=85) (9.7±7.0 vs. 15.8±10.9 µg/mL, p=0.001). Higher concentrations of apoB (p=0.017), apoB/A1 ratio (p<0.001), blood urea nitrogen (p=0.034), creatinine (p=0.003), and fasting insulin (p=0.004) were observed in HF patients with MetS compared with those without MetS. In HF patients with MetS, adiponectin concentrations were negatively correlated with hsCRP (r=-0.388, p=0.015) and positively correlated with the ratio of early mitral inflow velocity to early diastolic mitral annular velocity, E/E' (r=0.399, p=0.015). There was a significant trend towards decreased adiponectin concentrations with an increasing number of components of MetS (p for trend=0.012). Conclusion Our study demonstrated that adiponectin concentrations decreased in HF patients with MetS, and that relationship between adiponectin, inflammation and abnormal diastolic function, possibly leading to the progression of HF. PMID:22187237

  8. Association between the level of circulating adiponectin and prediabetes: A meta-analysis

    PubMed Central

    Lai, Huasheng; Lin, Nie; Xing, Zhenzhen; Weng, Huanhuan; Zhang, Hua

    2015-01-01

    Aims/Introduction Adiponectin has been proposed to have an essential role in the regulation of insulin sensitivity and metabolism, but previous studies on levels of adiponectin in prediabetes remain inconsistent. The present study aimed to assess the differences of adiponectin levels between prediabetes patients and healthy controls by carrying out a meta-analysis. Materials and Methods We carried out a systematic literature search of PubMed, EMBASE, and other databases for case–control studies and cohort studies measuring adiponectin levels in serum or plasma from prediabetes patients and healthy controls. The pooled weighted mean difference (WMD) and 95% confidence interval (CI) were used to estimate the association between adiponectin levels and prediabetes. Results Three cohort studies and 15 case–control studies with a total of 41,841 participants were included in the meta-analysis. The results showed that circulating adiponectin levels in prediabetes patients were significantly lower than that of healthy controls (WMD –1.694 μg/mL; 95% CI –2.151, –1.237; P < 0.001). Subgroup analysis showed more significant differences between prediabetes patients and healthy controls when the ratio of the homeostatic model assessment of insulin resistance was >2.12 (WMD −2.95 μg/mL; 95% CI –4.103, –1.806; P < 0.001) and average age was >60 years (WMD −2.20 μg/mL; 95% CI –3.207, –1.201; P < 0.001). Additionally, WMD in adiponectin showed a trend of direct correlation in subgroups of homeostatic model assessment of insulin resistance ratio, body mass index and age. Conclusions The present meta-analysis supports adiponectin levels in prediabetes patients being lower than that of healthy controls,indicating that the level of circulating adiponectin decreases before the onset of diabetes. PMID:26221520

  9. Serum Adiponectin Levels, Neuroimaging, and Cognition in the Mayo Clinic Study of Aging

    PubMed Central

    Wennberg, Alexandra M. V.; Gustafson, Deborah; Hagen, Clinton E.; Roberts, Rosebud O.; Knopman, David; Jack, Clifford; Petersen, Ronald C.; Mielke, Michelle M.

    2016-01-01

    BACKGROUND Adiponectin, a protein involved in inflammatory pathways, may impact the development and progression of Alzheimer’s disease (AD). Adiponectin levels have been associated with mild cognitive impairment (MCI) and AD; however, its association with Alzheimer-associated neuroimaging and cognitive outcomes is unknown. OBJECTIVE Determine the cross-sectional association between plasma adiponectin and neuroimaging and cognitive outcomes in an older population-based sample. METHODS Multivariable adjusted regression models were used to investigate the association between plasma adiponectin and hippocampal volume (HVa), PiB-PET, FDG PET, cortical thickness, MCI diagnosis, and neuropsychological test performance. Analyses included 535 non-demented participants aged 70 and older enrolled in the Mayo Clinic Study of Aging. RESULTS Women had higher adiponectin than men (12,631 ng/mL vs. 8,908 ng/mL, P < .001). Among women, higher adiponectin was associated with smaller HVa (B=−0.595; 95% CI −1.19, −0.005), poorer performance in language (B−0.676; 95% CI −1.23, −0.121) and global cognition (B=−0.459; 95% CI −0.915, −0.002), and greater odds of a MCI diagnosis (OR=6.23; 95% CI 1.20, 32.43). In analyses stratified by sex and elevated amyloid (PiB-PET SUVR>1.4), among women with elevated amyloid, higher adiponectin was associated with smaller HVa (B=−0.723; 95% CI −1.43, −0.014), poorer performance in memory (B=−1.02; 95% CI −1.73, −0.312), language (B=−0.896; 95% CI −1.58, −0.212), and global (B=−0.650; 95% CI −1.18, −0.116) cognition, and greater odds of MCI (OR=19.34; 95% CI 2.72, 137.34). CONCLUSION Higher plasma adiponectin was associated with neuroimaging and cognitive outcomes among women. Longitudinal analyses are necessary to determine whether higher adiponectin predicts neurodegeneration and cognitive decline. PMID:27163809

  10. Three-month treatment with pioglitazone reduces circulating C1q-binding adiponectin complex to total-adiponectin ratio, without changes in body mass index, in people with type 2 diabetes.

    PubMed

    Nakatsuji, Hideaki; Kishida, Ken; Kobayashi, Hironori; Funahashi, Tohru; Shimomura, Iichiro

    2013-01-01

    We measured circulating C1q-binding adiponectin (C1q-APN) levels before and after 3-month treatment with pioglitazone in people with type 2 diabetes. The results indicate 3-month treatment with pioglitazone reduces circulating levels of C1q-APN/total-adiponectin ratio without changes in body mass index.

  11. Subetta treatment increases adiponectin secretion by mature human adipocytes in vitro.

    PubMed

    Nicoll, Jim; Gorbunov, Evgeniy A; Tarasov, Sergey A; Epstein, Oleg I

    2013-01-01

    Purpose. To investigate the mechanism of action in peripheral tissues of novel complex drug containing release-active dilutions of antibodies to the beta subunit of the insulin receptor and antibodies to endothelial nitric oxide synthase (Subetta), which has shown efficacy in animal models of diabetes. Methods. Human mature adipocytes were incubated either with Subetta, with one of negative controls (placebo or vehicle), with one of nonspecific controls (release-active dilutions of antibodies to cannabinoid receptor type I or release-active dilutions of rabbit nonimmune serum), or with dimethyl sulfoxide (DMSO) at 37°C in a humidified incubator at 5% CO2 for three days. Rosiglitazone was used as reference drug. Secretion of adiponectin was measured by quantitative enzyme-linked immunosorbent assay (ELISA). Results. Only Subetta significantly stimulates adiponectin production by mature human adipocytes. Nonspecific controls did not significantly affect adiponectin secretion, resulting in adiponectin levels comparable to background values of the negative controls and DMSO. Conclusion. Increasing adiponectin production in absence of insulin by Subetta probably via modulating effect on the beta subunit of the insulin receptor might serve as one of the mechanisms of the antidiabetic effect of this drug. These in vitro results give first insight on possible mechanism of action of Subetta and serve as a background for further studies.

  12. Adiponectin induces A20 expression in adipose tissue to confer metabolic benefit.

    PubMed

    Hand, Laura E; Usan, Paola; Cooper, Garth J S; Xu, Lance Y; Ammori, Basil; Cunningham, Peter S; Aghamohammadzadeh, Reza; Soran, Handrean; Greenstein, Adam; Loudon, Andrew S I; Bechtold, David A; Ray, David W

    2015-01-01

    Obesity is a major risk factor for metabolic disease, with white adipose tissue (WAT) inflammation emerging as a key underlying pathology. We detail that mice lacking Reverbα exhibit enhanced fat storage without the predicted increased WAT inflammation or loss of insulin sensitivity. In contrast to most animal models of obesity and obese human patients, Reverbα(-/-) mice exhibit elevated serum adiponectin levels and increased adiponectin secretion from WAT explants in vitro, highlighting a potential anti-inflammatory role of this adipokine in hypertrophic WAT. Indeed, adiponectin was found to suppress primary macrophage responses to lipopolysaccharide and proinflammatory fatty acids, and this suppression depended on glycogen synthase kinase 3β activation and induction of A20. Attenuated inflammatory responses in Reverbα(-/-) WAT depots were associated with tonic elevation of A20 protein and ex vivo shown to depend on A20. We also demonstrate that adipose A20 expression in obese human subjects exhibits a negative correlation with measures of insulin sensitivity. Furthermore, bariatric surgery-induced weight loss was accompanied by enhanced WAT A20 expression, which is positively correlated with increased serum adiponectin and improved metabolic and inflammatory markers, including C-reactive protein. The findings identify A20 as a mediator of adiponectin anti-inflammatory action in WAT and a potential target for mitigating obesity-related pathology.

  13. Hypoglycemic effects of three Iranian edible plants; jujube, barberry and saffron: Correlation with serum adiponectin level.

    PubMed

    Hemmati, Mina; Asghari, Somaye; Zohoori, Elham; Karamian, Mehdi

    2015-11-01

    One of the most common disorders of the endocrine system is diabetes mellitus. This disease is associated with dyslipidemia. Adiponectin is a protein hormone that secreted by adipocytes and has an important role in regulating of glucose and fatty acid metabolic pathways. This study was designed to investigate the changes in serum level of adiponectin in diabetic rats treated with hydroalcoholic extracts of three medicinal plants; jujube (Ziziphus jujuba), barberry (Berberis vulgaris) and saffron (Crocus sativus) in comparison with quercetin. Streptozotocin -induced diabetic male rats were gavaged with specified doses of the extracts (25 and 100mg/kg) for two weeks. At the end of treatment period, fasting blood specimens were collected. The levels of adiponectin, fasting blood sugar (FBS), total Cholesterol, triglycerides, HDL-C and LDL-C were measured. Statistical analysis showed that serum levels of triglyceride and VLDL decreased significantly (P<0.05) in all treated groups. FBS level in all treated groups, decreased significantly and reach to normoglycemic level (P<0.05). Except Jujube, other plant extracts had no effect on cholesterol. Jujube in two doses (25 and 100mg/kg) could increased significantly HDL-C (P<0.05) with no effect on total cholesterol and LDL-C. Serum adiponectin level increased in all treated groups. These beneficial effects of C. sativus, B. vulgaris and Z. jujube extracts and quercetin in diabetic rats may be associated with increase in adiponectin level.

  14. Pioglitazone increases secretion of high-molecular-weight adiponectin from adipocytes.

    PubMed

    Bodles, Angela M; Banga, Anannya; Rasouli, Neda; Ono, Fumiyo; Kern, Philip A; Owens, Randall J

    2006-11-01

    Adiponectin is an adipocyte-derived serum protein that plays important roles in energy homeostasis, obesity, and insulin sensitivity. Using sucrose gradients and Western blotting of nondenaturing gels, we examined the adiponectin isoforms secreted from human adipose tissue, human and mouse adipocytes, and cell lines in response to pioglitazone added in vitro. The predominant form secreted from adipose tissue in vitro was the high-molecular-weight (HMW) isoform, with small amounts of low-molecular-weight (LMW) forms present. The addition of pioglitazone (1-3 micromM) in vitro increased the secretion of the HMW isoform, with no significant effect on the other isoforms. Human adipose tissue was also examined for changes in adiponectin mRNA levels upon pioglitazone treatment. No difference was detected, suggesting that the effect of pioglitazone is not at the transcriptional level but, rather, at a posttranscriptional phase of the secretory pathway. Additional experiments were conducted to determine whether adiponectin expression was mechanistically similar in other adipose cells. Examination of primary human adipocytes revealed an increase in intracellular HMW isoform with a decline in LMW forms following pioglitazone treatment, with a corresponding increase in the secreted HMW form. Similar results were observed with primary mouse adipocytes, 3T3-F422A cells, and SGBS human adipocyte cells, although differences in the distribution of HMW and LMW isoforms were apparent between cell types. Although there are differences in isoforms between species, in all cases pioglitazone served to increase the secretion of the HMW form of adiponectin.

  15. The regulation of adiponectin receptors in human prostate cancer cell lines

    SciTech Connect

    Mistry, T.; Digby, J.E.; Chen, J.; Desai, K.M.; Randeva, H.S. . E-mail: H.Randeva@warwick.ac.uk

    2006-09-29

    Obesity is a risk factor for prostate cancer, and plasma levels of the adipokine, adiponectin, are low in the former but high in the latter. Adiponectin has been shown to modulate cell proliferation and apoptosis, suggesting that adiponectin and its receptors (Adipo-R1, Adipo-R2) may provide a molecular association between obesity and prostate carcinogenesis. We show for First time, the protein distribution of Adipo-R1 and Adipo-R2 in LNCaP and PC3 cells, and in human prostate tissue. Using real-time RT-PCR we provide novel data demonstrating the differential regulation of Adipo-R1 and Adipo-R2 mRNA expression by testosterone, 5-{alpha} dihydrotestosterone, {beta}-estradiol, tumour necrosis factor-{alpha}, leptin, and adiponectin in LNCaP and PC3 cells. Our findings suggest that adiponectin and its receptors may contribute to the molecular association between obesity and prostate cancer through a complex interaction with other hormones and cytokines that also play important roles in the pathophysiology of obesity and prostate cancer.

  16. Adiponectin stimulates Wnt inhibitory factor-1 expression through epigenetic regulations involving the transcription factor specificity protein 1.

    PubMed

    Liu, Jing; Lam, Janice B B; Chow, Kim H M; Xu, Aimin; Lam, Karen S L; Moon, Randall T; Wang, Yu

    2008-11-01

    Adiponectin (ADN) is an adipokine possessing growth inhibitory activities against various types of cancer cells. Our previous results demonstrated that ADN could impede Wnt/beta-catenin-signaling pathways in MDA-MB-231 human breast carcinoma cells [Wang,Y. et al. (2006) Adiponectin modulates the glycogen synthase kinase-3 beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice. Cancer Res., 66, 11462-11470]. Here, we extended our studies to elucidate the effects of ADN on regulating the expressions of Wnt inhibitory factor-1 (WIF1), a Wnt antagonist frequently silenced in human breast tumors. Our results showed that ADN time dependently stimulated WIF1 gene and protein expressions in MDA-MB-231 cells. Overexpression of WIF1 exerted similar inhibitory effects to those of ADN on cell proliferations, nuclear beta-catenin activities, cyclin D1 expressions and serum-induced phosphorylations of Akt and glycogen synthase kinase-3 beta. Blockage of WIF1 activities significantly attenuated the suppressive effects of ADN on MDA-MB-231 cell growth. Furthermore, our in vivo studies showed that both supplementation of recombinant ADN and adenovirus-mediated overexpression of this adipokine substantially enhanced WIF1 expressions in MDA-MB-231 tumors implanted in nude mice. More interestingly, we found that ADN could alleviate methylation of CpG islands located within the proximal promoter region of WIF1, possibly involving the specificity protein 1 (Sp1) transcription factor and its downstream target DNA methyltransferase 1 (DNMT1). Upon ADN treatment, the protein levels of both Sp1 and DNMT1 were significantly decreased. Using silencing RNA approaches, we confirmed that downregulation of Sp1 resulted in an increased expression of WIF1 and decreased methylation of WIF1 promoter. Taken together, these data suggest that ADN might elicit its antitumor activities at least partially through promoting WIF1 expressions.

  17. Regulation of lipin1 by nutritional status, adiponectin, sex and pituitary function in rat white adipose tissue.

    PubMed

    González, C Ruth; Novelle, Marta G; Caminos, Jorge E; Vázquez, María J; Luque, Raul M; López, Miguel; Nogueiras, Ruben; Diéguez, Carlos

    2012-02-01

    Lipin1 is a member of the lipin protein family that plays an important role in the regulation of lipid metabolism. The endogenous role of lipin1 was demonstrated by the fact that mutations in lipin1 caused lipodystrophy and metabolic disorders. The aim of this study was to assess the influence of nutritional status, pregnancy, insulin-sensitizers and pituitary hormones on lipin1 mRNA levels in adipose tissue of rats. Lipin1 gene expression was induced in conditions of hypoleptinemia (fasting) and leptin resistance (high fat diet), whereas it was decreased by high circulating leptin levels (leptin administration, pregnancy) and in leptin-deficient mice. Lipin1 mRNA levels were also decreased in adiponectin-deficient mice. Lipin1 mRNA levels are influenced by age in female rats, with peak expression at 25th day of life and decreasing thereafter. Consistently, ovariectomy increased lipin1 expression indicating that estrogens modulate lipin1. Finally, lipin1 was also regulated by pituitary hormones, since its expression was modified by thyroid status and growth hormone deficiency. Our observations indicate that: a) gWAT lipin1 mRNA levels are regulated by nutritional status, and leptin plays an important role in this regard, b) lipin1 is modulated by adiponectin, c) lipin1 is influenced by age and sex, and d) alterations in pituitary function modify lipin1 mRNA levels. To dissect the complicated interactions between key regulators of lipid metabolism like lipin1, may be important for the development of new therapies for the treatment and prevention of obesity and its associated disorders.

  18. Carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults in the Framingham Offspring Cohort

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diet may influence circulating adiponectin levels by improving insulin sensitivity. We examined the associations between carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults aged 26–81 y (n= 979 men and 1227 women). Dietary intakes were assessed using a FFQ. Fasting...

  19. Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adiponectin is an adipose-secreted protein that has been linked to changes in insulin sensitivity, high-density lipoprotein cholesterol levels, and inflammatory patterns. Although fenofibrate therapy can raise adiponectin levels, treatment response is heterogeneous and heritable, suggesting a role f...

  20. Study of Adiponectin Level in Diabetic Adolescent Girls in Relation to Glycemic Control and Complication of Diabetes

    PubMed Central

    Dayem, Soha M. Abd El; Nazif, Hayam K.; EI-Kader, Mona Abd; El-Tawil, Maha

    2015-01-01

    AIM: To study the relation between adiponectin level with glycemic control and complication of diabetes. PATIENTS AND METHODS: The study included 40 female adolescent type 1 diabetic patients and 40 healthy volunteers of the same age and sex. Blood sample was taken for assessment of glycosylated hemoglobin, lipid profile and adiponectine. Urine sample was taken for assessment of albumin/creatinine ratio. RESULTS: Diabetic patients had a significantly higher diastolic blood pressure, triglyceride, total cholesterol, LDL and adiponectin than controls. Patients with diabetes complication had a significant lower BMI and HDL. On the other hand, they had higher disease duration, total cholesterol, HbA1, albumin/creatinine ratio and adiponectin. Patients with microalbuminuria had a lower BMI, higher disease duration, diastolic blood pressure and adiponectin. Patients with diabetic retinopathy had higher disease duration, insulin dose, HbA1, microalbuminuria and adiponectin. Adiponectin in diabetic patients had a significant negative correlation with BMI and positive correlation with systolic blood pressure and microlabuminuria. CONCLUSION: Serum adiponectin level is high in adolescent type 1 diabetic girls. It can be used as a predictor of diabetes complications rather than a sensitive biochemical marker for glycemic control. PMID:27275296

  1. Clinical insights from adiponectin analysis in breast cancer patients reveal its anti-inflammatory properties in non-obese women.

    PubMed

    Panis, C; Herrera, A C S A; Aranome, A M F; Victorino, V J; Michelleti, P L; Morimoto, H K; Cecchini, A L; Simão, A N C; Cecchini, R

    2014-01-25

    Adiponectin is a cytokine reported as a determinant of poor prognosis in women with breast cancer. However, because data regarding its role in breast cancer have been obtained primarily from studies employing overweight or obese women, the adiponectin profile in non-obese women is poorly understood. In this study, we determined adiponectin levels in plasma from non-obese women with breast cancer and investigated a possible correlation with systemic inflammatory status. We determined the plasma adiponectin levels as well as biochemical and oxidative stress parameters in 80 women. Our results revealed that plasma adiponectin levels were affected by chemotherapy, estrogen receptor status, and disease progression. Adiponectin was positively correlated with antioxidant levels, without affecting either the metastatic behavior of disease or patient outcome. These findings highlight adiponectin as a novel player in the endocrine signaling that modulates the oxidative inflammatory response in human breast cancer, and contribute to the understanding of the role of adiponectin in pathological conditions in non-obese women.

  2. Association between adipose tissue expression and serum levels of leptin and adiponectin in women with polycystic ovary syndrome.

    PubMed

    Lecke, S B; Morsch, D M; Spritzer, P M

    2013-02-28

    We reviewed emerging evidence linking serum levels and adipose tissue expression of leptin and adiponectin in women with polycystic ovary syndrome (PCOS). Previous data obtained by our group from a sample of overweight/obese PCOS women and a control sample of normal weight controls, both stratified by BMI, were reanalyzed. Circulating levels of leptin and adiponectin were determined by commercially available enzyme-linked immunosorbent assays. Adipose tissue total RNA was reserve-transcripted into complementary DNA samples, which were used as templates for quantitative real-time PCR amplification. Positive correlations were found between serum and mRNA levels for both leptin (r = 0.321; P = 0.005) and adiponectin (r = 0.266; P = 0.024). Determination of leptin and adiponectin serum levels could serve as an indirect method to assess adipocyte production, since leptin and adiponectin are predominantly produced by subcutaneous adipocytes in women.

  3. Disturbed adiponectin – AMPK system in skeletal muscle of patients with metabolic syndrome.

    PubMed

    Van Berendoncks, An M; Stensvold, Dorthe; Garnier, Anne; Fortin, Dominique; Sente, Tahnee; Vrints, Christiaan J; Arild, Slørdahl Stig; Ventura-Clapier, Renee; Wisløff, Ulrik; Conraads, Viviane M

    2015-02-01

    Patients with metabolic syndrome are characterized by low circulating adiponectin levels and reduced adiponectin sensitivity in skeletal muscles. Through binding on its main skeletal muscle receptor AdipoR1, adiponectin activates AMP-activated protein kinase (AMPK), a key player in energy homeostasis. Fourteen metabolic syndrome patients and seven healthy control subjects were included. Blood samples were taken to determine insulin resistance, adiponectin, lipoproteins, and C-reactive protein. Muscle biopsies (m. vastus lateralis) were obtained to assess mRNA expression of AdipoR1 and both AMPKα1 and AMPKα2 subunits, as well as downstream targets in lipid and glucose metabolism. Skeletal muscle mRNA expression of AMPKα1 and AMPKα2 was lower in metabolic syndrome patients (100 ± 6 vs. 122 ± 8 AU, p = 0.030 and 64 ± 4 vs. 85 ± 9 AU, p = 0.044, respectively), whereas the expression of AdipoR1 was upregulated (138 ± 9 vs. 105 ± 7, p = 0.012). AMPKα1 and AdipoR1 correlated positively in both the control (r = 0.964, p < 0.001) and the metabolic syndrome group (r = 0.600, p = 0.023). However, this relation was shifted upwards in metabolic syndrome patients, indicating increased AdipoR1mRNA expression for a similar AMPKα1 expression. Previously, a blunted stimulatory effect of adiponectin on AMPK activation has been shown in metabolic syndrome patients. The present data suggest that the disturbed interaction of adiponectin with AMPK is located downstream of the AdipoR1 receptor.

  4. Adiponectin, leptin and IL-1 β in elderly diabetic patients with mild cognitive impairment.

    PubMed

    Gorska-Ciebiada, Malgorzata; Saryusz-Wolska, Malgorzata; Borkowska, Anna; Ciebiada, Maciej; Loba, Jerzy

    2016-04-01

    The aim of the study was to determine the serum levels of adiponectin, leptin and IL-1 β in elderly diabetic patients with and without mild cognitive impairment (MCI) and to examine the associations of these markers with clinical and cognitive parameters. A biochemical evaluation was performed of 62 seniors with type 2 diabetes (T2DM) and MCI, and 132 seniors with T2DM but without MCI (controls). Serum leptin and IL-1 β levels were higher and adiponectin concentration was lower in MCI patients than controls. In MCI subjects, adiponectin level was negatively correlated with leptin, IL-1 β levels and BMI. Leptin concentration was correlated with IL-1 β level. Univariate logistic regression models revealed that the factors which increased the likelihood of diagnosis of MCI in elderly patients with T2DM were higher levels of HbA1c, leptin, IL-1 β and triglycerides, as well as lower levels of adiponectin and HDL cholesterol. Similarly, previous CVD, hypertension, hyperlipidemia, retinopathy, nephropathy, hypoglycemia, longer duration of diabetes, increased number of co-morbidities, older age, fewer years of formal education were found to be associated with MCI. The multivariable model indicated fewer years of formal education, previous CVD, hypertension, increased number of co-morbidities, higher HbA1c and IL-1 β levels and lower adiponectin level. Elderly diabetic patients with MCI have higher levels of leptin and IL-1 β and lower levels of adiponectin. Further prospective studies are needed to determine the role of these markers in the progression to dementia.

  5. Adiponectin Receptors Form Homomers and Heteromers Exhibiting Distinct Ligand Binding and Intracellular Signaling Properties*

    PubMed Central

    Almabouada, Farid; Diaz-Ruiz, Alberto; Rabanal-Ruiz, Yoana; Peinado, Juan R.; Vazquez-Martinez, Rafael; Malagon, Maria M.

    2013-01-01

    Adiponectin binds to two widely expressed receptors (AdipoR1 and AdipoR2) that contain seven transmembrane domains but, unlike G-protein coupled receptors, present an extracellular C terminus and a cytosolic N terminus. Recently, AdipoR1 was found to associate in high order complexes. However, it is still unknown whether AdipoR2 may also form homomers or heteromers with AdipoR1 or if such interactions may be functionally relevant. Herein, we have analyzed the oligomerization pattern of AdipoRs by FRET and immunoprecipitation and evaluated both the internalization of AdipoRs in response to various adiponectin isoforms and the effect of adiponectin binding to different AdipoR combinations on AMP-activated protein kinase phosphorylation and peroxisome proliferator-activated receptor α activation. Transfection of HEK293AD cells with AdipoR1 and AdipoR2 showed that both receptors colocalize at both the plasma membrane and the endoplasmic reticulum. Co-transfection with the different AdipoR pairs yielded high FRET efficiencies in non-stimulated cells, which indicates that AdipoR1 and AdipoR2 form homo- and heteromeric complexes under resting conditions. Live FRET imaging suggested that both homo- and heteromeric AdipoR complexes dissociate in response to adiponectin, but heteromers separate faster than homomers. Finally, phosphorylation of AMP-activated protein kinase in response to adiponectin was delayed in cells wherein heteromer formation was favored. In sum, our findings indicate that AdipoR1 and AdipoR2 form homo- and heteromers that present unique interaction behaviors and signaling properties. This raises the possibility that the pleiotropic, tissue-dependent functions of adiponectin depend on the expression levels of AdipoR1 and AdipoR2 and, therefore, on the steady-state proportion of homo- and heteromeric complexes. PMID:23255609

  6. Serum Adiponectin Level and Clinical, Metabolic, and Hormonal Markers in Patients with Polycystic Ovary Syndrome

    PubMed Central

    Yildiz, Yunus; Ozaksit, Gülnur; Serdar Unlu, Bekir; Ozgu, Emre; Energin, Hasan; Kaba, Metin; Ugur, Mustafa

    2014-01-01

    Background: To investigate the relationship between adiponectin, metabolic and hor- monal parameters, and insulin resistance in patients with non-treated polycystic ovary syndrome. Materials and Methods: In this cross-sectional observational study, 81 patients admitted to out-patient clinic with complaints of menstrual irregularity, hirsutism and obesity were enrolled. Serum adiponectin, biochemical and hormonal parameters, and 75 gram oral glu- cose tolerance test (OGTT) were measured. Spearman’s correlation coefficient was used for statistical analysis. Results: We observed inverse correlations between serum adiponectin level and body mass index, homeostasis model assessment insulin-resistance score, insulin level, fast- ing glucose level, and prolactin level (p=0.001, p=0.02, p=0.04, p=0.02, and p=0.005, respectively). No significant correlations were found between serum adiponectin level and age, height, weight, Ferriman-Gallwey score, 2 hours OGTT test value and free tes- tosterone level (p=0.3, p=0.6, p=0.2, p=0.8, p=0.9, and p=0.01, respectively). Conclusion: The present study demonstrated that in polycystic ovary syndrome patients, when serum adiponectin level decreased, degree of insulin resistance increased. Our find- ings indicate that serum adiponectin level is likely to be an adequate marker for deter- mination of the degree of insulin resistance, and may be a predictor of diseases, such as type 2 diabetes mellitus (T2DM) and metabolic syndrome, which develop on the basis of insulin resistance. PMID:24520503

  7. Optimization of adiponectin-derived peptides for inhibition of cancer cell growth and signaling.

    PubMed

    Otvos, Laszlo; Kovalszky, Ilona; Olah, Julia; Coroniti, Roberta; Knappe, Daniel; Nollmann, Friederike I; Hoffmann, Ralf; Wade, John D; Lovas, Sandor; Surmacz, Eva

    2015-05-01

    Adiponectin, an adipose tissue-excreted adipokine plays protective roles in metabolic and cardiovascular diseases and exerts anti-cancer activities, partially by interfering with leptin-induced signaling. Previously we identified the active site in the adiponectin protein, and generated both a nanomolar monomeric agonist of the adiponectin receptor (10-mer ADP355) and an antagonist (8-mer ADP400) to modulate various adiponectin receptor-mediated cellular functions. As physiologically circulating adiponectin forms multimeric complexes, we also generated an agonist dimer with improved biodistribution and in vitro efficacy. In the current report, we attempted to optimize the monomeric agonist structure. Neither extension of the peptide up to 14-mer analogs nor reinstallation of native residues in permissible positions enhanced significantly the activity profile. The only substitutions that resulted in 5-10-fold improved agonistic activity were the replacement of turn-forming Gly4 and Tyr7 residues with Pro and Hyp, respectively, yielding the more active native β-sheet structure. All peptides retained good stability in human serum exhibiting half-lives >2 h. The cellular efficacy and stability rankings among the peptides followed expected structure-activity relationship trends. To investigate whether simultaneous activation of adiponectin pathways and inhibition of leptin-induced signals can result in cytostatic and anti-oncogenic signal transduction processes, we developed a chimera of the leptin receptor antagonist peptide Allo-aca (placed to the N-terminus) and ADP355 (at the C-terminus). The in vitro anti-tumor activity and intracellular signaling of the chimera were dominated by the more active Allo-aca component. The ADP355 part, however, reversed unfavorable in vivo metabolic effects of the leptin receptor antagonist.

  8. In humans the adiponectin receptor R2 is expressed predominantly in adipose tissue and linked to the adipose tissue expression of MMIF-1.

    PubMed

    Kos, K; Wong, S P Y; Huda, M S B; Cakir, M; Jernas, M; Carlsson, L; Kerrigan, D; Wilding, J P H; Pinkney, J H

    2010-04-01

    In this study, the regional adipose tissue-adiponectin (AT-ADN) and adiponectin receptor (R1 and R2) expression and their relation with metabolic parameters, circulating and AT-derived cytokine expressions were compared. Paired subcutaneous adipose tissue (SCAT) and visceral adipose tissue (VAT) were taken from 18 lean and 39 obese humans, AT-mRNA expression of adipokines analysed by RT-PCR and corresponding serum levels by enzyme-linked immunosorbent assay (ELISA). R1 and R2 adipocyte expression was compared with 17 other human tissues. ADN-gene expression was lower in VAT than SCAT [mean (SD) 1.54 (1.1) vs. 2.84 (0.87); p < 0.001], and lower in obese subjects (VAT : p = 0.01;SCAT : p < 0.001). SCAT-ADN correlated positively with serum ADN (r = 0.33;p = 0.036) but not VAT-ADN. AT expressions of ADN and macrophage migration inhibiting factor (MMIF), IL18 and cluster of differentiation factor 14 (CD14) in both depots showed inverse correlations. R1 and R2 were expressed ubiquitously and R2 highest in SCAT, and this is much higher (x100) than R1 (x100). R expression was similar in lean and obese subjects and unrelated to the metabolic syndrome, however, receptors correlated with VAT-MMIF (R 1: r = 0.4;p = 0.008;R 2: r = 0.35,p = 0.02) and SCAT-MMIF expression (R 2: r = 0.43;p = 0.004). Unlike ADN, its receptors are expressed in many human tissues. Human R2 expression is not highest in the liver but in AT where it is associated with MMIF expression. The adiponectin-dependent insulin-sensitizing action of thiazolidinediones is thus probably to differ amongst species with weaker effects on the human liver.

  9. Adiponectin Potentially Contributes to the Antidepressive Effects of Baduanjin Qigong Exercise in Women With Chronic Fatigue Syndrome-Like Illness.

    PubMed

    Chan, Jessie S M; Li, Ang; Ng, Siu-Man; Ho, Rainbow T H; Xu, Aimin; Yao, Tzy-Jyun; Wang, Xiao-Min; So, Kwok-Fai; Chan, Cecilia L W

    2017-03-13

    Our recent study demonstrates that adiponectin signaling plays a significant role in mediating physical exercise-exerted effects on hippocampal neurogenesis and antidepression in mice. Whether the findings can be translated to humans remains unknown. This study aimed to investigate the effects of Baduanjin Qigong exercise on adiponectin and to evaluate whether adiponectin is involved in the antidepressive effects of Qigong exercise on chronic fatigue syndrome (CFS)-like illness. This is a randomized, waitlist-controlled trial. One hundred eight female participants were randomly assigned to either Qigong exercise or waitlist groups. Sixteen 1.5-h Qigong lessons were conducted. Outcome measures were taken at three time points. Baseline adiponectin levels were negatively associated with body weight, body mass index, waist circumference, hip circumference, and waist/hip ratio in women with CFS-like illness. Compared with the waitlist control, Qigong exercise significantly reduced anxiety and depression symptoms and significantly raised plasma adiponectin levels (median = 0.8 vs. -0.1, p < 0.05). More interestingly, increases in adiponectin levels following Qigong exercise were associated with decreases in depression scores for the Qigong group (r = -0.38, p = 0.04). Moreover, adjusted linear regression analysis further identified Qigong exercise and change in adiponectin levels as the significant factors accounting for reduction of depression symptoms. Baduanjin Qigong significantly increased adiponectin levels in females with CFS-like illness. Decreases in depression symptoms were associated with increases in adiponectin levels following Qigong exercise, indicating that the potential contribution of adiponectin to Qigong exercise elicited antidepressive effects in human subjects.

  10. Inhibitory role of adiponectin peptide I on rat choroidal neovascularization

    PubMed Central

    Lyzogubov, Valeriy V.; Tytarenko, Ruslana G.; Bora, Nalini S.; Bora, Puran S.

    2013-01-01

    Age-related macular degeneration (AMD) is a leading cause of central blindness in elderly population. Wet type of AMD is characterized by extensive growth of new vessels. One of the effective strategies to treat wet AMD is to limit the choroidal neovascularization (CNV). We studied effect of adiponectin peptide I (APNpI) on new vessel growth in laser-induced rat model of wet AMD and on rat choroidal endothelial cell (CEC) culture. CNV size and vessel density was investigated by microscopy. Immunohistochemical staining (IHC) for Von Willebrand Factor (vWF), APN, APN receptors 1 (AdipoR1), 2 (AdipoR2), VEGF, VEGF receptor 2 (VEGF-R2), proliferating cell nuclear antigen (PCNA) was performed in CNV area. The mRNA expression of VEGF and VEGF-R2 in RPE-choroid was investigated by RT-PCR and real-time PCR. APNpI inhibited area of CNV by 4 fold, number of vWF positive vessels by 99% and area of subretinal tissue by 40%. The expression of VEGF and VEGF-R2 at mRNA and protein levels were decreased after APNpI treatment in vivo. Proliferative index (PCNA) was 5 fold less in laser spots of APNpI treated rats compared to controls. In conclusion, APNpI inhibited formation of new vessels in rat model of CNV by decreasing VEGF, VEGF-R2 expression and cell proliferation. Thus, APNpI may have potential therapeutic use for AMD treatment since it significantly inhibited CNV. PMID:22633972

  11. Tumor expression of adiponectin receptor 2 and lethal prostate cancer

    PubMed Central

    Fiorentino, Michelangelo; Kelly, Rachel; Gerke, Travis; Jordahl, Kristina; Sinnott, Jennifer A.; Giovannucci, Edward L.; Loda, Massimo; Mucci, Lorelei A.; Finn, Stephen

    2015-01-01

    To investigate the role of adiponectin receptor 2 (AdipoR2) in aggressive prostate cancer we used immunohistochemistry to characterize AdipoR2 protein expression in tumor tissue for 866 men with prostate cancer from the Physicians’ Health Study and the Health Professionals Follow-up Study. AdipoR2 tumor expression was not associated with measures of obesity, pathological tumor stage or prostate-specific antigen (PSA) at diagnosis. However, AdipoR2 expression was positively associated with proliferation as measured by Ki-67 expression quartiles (P-trend < 0.0001), with expression of fatty acid synthase (P-trend = 0.001), and with two measures of angiogenesis (P-trend < 0.1). An inverse association was observed with apoptosis as assessed by the TUNEL assay (P-trend = 0.006). Using Cox proportional hazards regression and controlling for age at diagnosis, Gleason score, year of diagnosis category, cohort and baseline BMI, we identified a statistically significant trend for the association between quartile of AdipoR2 expression and lethal prostate cancer (P-trend = 0.02). The hazard ratio for lethal prostate cancer for the two highest quartiles, as compared to the two lowest quartiles, of AdipoR2 expression was 1.9 (95% confidence interval [CI]: 1.2–3.0). Results were similar when additionally controlling for categories of PSA at diagnosis and Ki-67 expression quartiles. These results strengthen the evidence for the role of AdipoR2 in prostate cancer progression. PMID:25863129

  12. Novel immunomodulatory effects of adiponectin on dendritic cell functions.

    PubMed

    Tsang, Julia Yuen Shan; Li, Daxu; Ho, Derek; Peng, Jiao; Xu, Aimin; Lamb, Jonathan; Chen, Yan; Tam, Paul Kwong Hang

    2011-05-01

    Adiponectin (ADN) is an adipocytokine with anti-inflammatory properties. Although it has been reported that ADN can inhibit the immunostimulatory function of monocytes and macrophages, little is known of its effect on dendritic cells (DC). Recent data suggest that ADN can regulate immune responses. DCs are uniquely specialised antigen presenting cells that play a central role in the initiation of immunity and tolerance. In this study, we have investigated the immuno- modulatory effects of ADN on DC functions. We found that ADN has only moderate effect on the differentiation of murine bone marrow (BM) derived DCs but altered the phenotype of DCs. The expression of major histocompatibilty complex class II (MHCII), CD80 and CD86 on ADN conditioned DCs (ADN-DCs) was lower than that on untreated cells. The production of IL-12p40 was also suppressed in ADN-DCs. Interestingly, ADN treated DCs showed an increase in the expression of the inhibitory molecule, programmed death-1 ligand (PDL-1) compared to untreated cells. In vitro co-culture of ADN-DCs with allogeneic T cells led to a decrease in T cell proliferation and reduction of IL-2 production. Concomitant with that, a higher percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) was detected in co-cultures of T cells and ADN-DCs. Blocking PD-1/PDL-1 pathway could partially restore T cell function. These findings suggest that the immunomodulatory effect of ADN on immune responses could be at least partially be mediated by its ability to alter DC function. The PD-1/PDL-1 pathway and the enhancement of Treg expansion are implicated in the immunomodulatory mechanisms.

  13. Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses.

    PubMed

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-09-01

    Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle microvascular recruitment. We demonstrated that a high-fat diet induces vascular adiponectin and insulin resistance but globular adiponectin administration can restore vascular insulin responses and improve insulin's metabolic action via an AMPK- and nitric oxide-dependent mechanism. This suggests that globular adiponectin might have a therapeutic potential for improving insulin resistance and preventing cardiovascular complications in patients with diabetes via modulation of microvascular insulin responses. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague-Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by

  14. Epigenetic Modulation in Periodontitis: Interaction of Adiponectin and JMJD3-IRF4 Axis in Macrophages.

    PubMed

    Xuan, Dongying; Han, Qianqian; Tu, Qisheng; Zhang, Lan; Yu, Liming; Murry, Dana; Tu, Tianchi; Tang, Yin; Lian, Jane B; Stein, Gary S; Valverde, Paloma; Zhang, Jincai; Chen, Jake

    2016-05-01

    Emerging evidence suggests an important role for epigenetic mechanisms in modulating signals during macrophage polarization and inflammation. JMJD3, a JmjC family histone demethylase necessary for M2 polarization is also required for effective induction of multiple M1 genes by lipopolysaccharide (LPS). However, the effects of JMJD3 to inflammation in the context of obesity remains unknown. To address this deficiency, we firstly examined the expression of JMJD3 in macrophage isolated from bone marrow and adipose tissue of diet induced obesity (DIO) mice. The results indicated that JMJD3 was down-regulated in obesity. Adiponectin (APN), a factor secreted by adipose tissue which is down-regulated in obesity, functions to switch macrophage polarization from M1 to M2, thereby attenuating chronic inflammation. Intriguingly, our results indicated that APN contributed to JMJD3 up-regulation, reduced macrophage infiltration in obese adipose tissue, and abolished the up-regulation of JMJD3 in peritoneal macrophages isolated from DIO mice when challenged with Porphyromonas gingivalis LPS (pg.lps). To elucidate the interaction of APN and JMJD3 involved in macrophage transformation in the context of inflammation, we designed the loss and gain-function experiments of APN in vivo with APN(-/-) mice with experimental periodontitis and in vitro with macrophage isolated from APN(-/-) mice. For the first time, we found that APN can help to reduce periodontitis-related bone loss, modulate JMJD3 and IRF4 expression, and macrophage infiltration. Therefore, it can be inferred that APN may contribute to anti-inflammation macrophage polarization by regulating JMJD3 expression, which provides a basis for macrophage-centered epigenetic therapeutic strategies.

  15. Expression of Progesterone Receptor Membrane Component 1 (PGRMC1), Progestin and AdipoQ Receptor 7 (PAQPR7), and Plasminogen Activator Inhibitor 1 RNA-Binding Protein (PAIRBP1) in Glioma Spheroids In Vitro

    PubMed Central

    Hlavaty, Juraj; Ertl, Reinhard; Miller, Ingrid; Gabriel, Cordula

    2016-01-01

    Objective. Some effects of progesterone on glioma cells can be explained through the slow, genomic mediated response via nuclear receptors; the other effects suggest potential role of a fast, nongenomic action mediated by membrane-associated progesterone receptors. Methods. The effects of progesterone treatment on the expression levels of progesterone receptor membrane component 1 (PGRMC1), plasminogen activator inhibitor 1 RNA-binding protein (PAIRBP1), and progestin and adipoQ receptor 7 (PAQR7) on both mRNA and protein levels were investigated in spheroids derived from human glioma cell lines U-87 MG and LN-229. Results. The only significant alteration at the transcript level was the decrease in PGRMC1 mRNA observed in LN-229 spheroids treated with 30 ng/mL of progesterone. No visible alterations at the protein levels were observed using immunohistochemical analysis. Stimulation of U-87 MG spheroids resulted in an increase of PGRMC1 but a decrease of PAIRBP1 protein. Double immunofluorescent detection of PGRMC1 and PAIRBP1 identified the two proteins to be partially colocalized in the cells. Western blot analysis revealed the expected bands for PGRMC1 and PAIRBP1, whereas two bands were detected for PAQR7. Conclusion. The progesterone action is supposed to be mediated via membrane-associated progesterone receptors as the nuclear progesterone receptor was absent in tested spheroids. PMID:27340667

  16. Expression of Progesterone Receptor Membrane Component 1 (PGRMC1), Progestin and AdipoQ Receptor 7 (PAQPR7), and Plasminogen Activator Inhibitor 1 RNA-Binding Protein (PAIRBP1) in Glioma Spheroids In Vitro.

    PubMed

    Hlavaty, Juraj; Ertl, Reinhard; Miller, Ingrid; Gabriel, Cordula

    2016-01-01

    Objective. Some effects of progesterone on glioma cells can be explained through the slow, genomic mediated response via nuclear receptors; the other effects suggest potential role of a fast, nongenomic action mediated by membrane-associated progesterone receptors. Methods. The effects of progesterone treatment on the expression levels of progesterone receptor membrane component 1 (PGRMC1), plasminogen activator inhibitor 1 RNA-binding protein (PAIRBP1), and progestin and adipoQ receptor 7 (PAQR7) on both mRNA and protein levels were investigated in spheroids derived from human glioma cell lines U-87 MG and LN-229. Results. The only significant alteration at the transcript level was the decrease in PGRMC1 mRNA observed in LN-229 spheroids treated with 30 ng/mL of progesterone. No visible alterations at the protein levels were observed using immunohistochemical analysis. Stimulation of U-87 MG spheroids resulted in an increase of PGRMC1 but a decrease of PAIRBP1 protein. Double immunofluorescent detection of PGRMC1 and PAIRBP1 identified the two proteins to be partially colocalized in the cells. Western blot analysis revealed the expected bands for PGRMC1 and PAIRBP1, whereas two bands were detected for PAQR7. Conclusion. The progesterone action is supposed to be mediated via membrane-associated progesterone receptors as the nuclear progesterone receptor was absent in tested spheroids.

  17. Adiponectin concentration is associated with muscle insulin sensitivity, AMPK phosphorylation, and ceramide content in skeletal muscles of men but not women.

    PubMed

    Høeg, Louise D; Sjøberg, Kim A; Lundsgaard, Anne-Marie; Jordy, Andreas B; Hiscock, Natalie; Wojtaszewski, Jørgen F P; Richter, Erik A; Kiens, Bente

    2013-03-01

    Adiponectin is an adipokine that regulates metabolism and increases insulin sensitivity. Mechanisms behind this insulin-sensitizing effect have been investigated in rodents, but little is known in humans, especially in skeletal muscle. Women have higher serum concentrations of adiponectin than men and are generally more insulin sensitive in skeletal muscle than men. We show here that large differences exist between men and women with regard to apparent adiponectin regulation of insulin-stimulated glucose uptake in skeletal muscle. Serum adiponectin was significantly associated with leg glucose uptake in healthy, young, lean men, but the association was absent in women. In addition, serum adiponectin was significantly associated with AMP-activated protein kinase (AMPK) phosphorylation in skeletal muscles of men but not in women. Serum adiponectin was also significantly, negatively associated with skeletal muscle ceramide content in men only, and interestingly, ceramide content was negatively associated with adiponectin receptor 1 (AdipoR1) expression in skeletal muscles of men. Women had lower AdipoR1 expression in skeletal muscle and a lower percentage of glycolytic adiponectin-sensitive type 2 muscle fibers than men. These associations suggest that the insulin-sensitizing effect of adiponectin on human male skeletal muscles may be mediated via AdipoR1 to activation of AMPK, leading to lowering of ceramide content. The lower skeletal muscle AdipoR1 protein expression and lower expression of adiponectin-sensitive type 2 muscle fibers in women than in men may explain the apparent lesser sensitivity to adiponectin in women.

  18. Effect of Extended-Release Niacin/Laropiprant Combination on Plasma Adiponectin and Insulin Resistance in Chinese Patients with Dyslipidaemia

    PubMed Central

    Yang, Ya-Ling; Masuda, Daisaku; Yamashita, Shizuya; Tomlinson, Brian

    2015-01-01

    Objectives. This study examined whether the increase of adiponectin associated with extended-release (ER) niacin/laropiprant combination attenuates the adverse effect of niacin on glucose and insulin resistance in Hong Kong Chinese patients with dyslipidaemia. Methods. Patients (N = 121) were treated with ER niacin/laropiprant 1 g/20 mg for 4 weeks and then the dose was doubled for an additional 8 weeks. Measurements of fasting lipids, glucose, insulin, and adiponectin were performed at baseline and during the study. Results. There were significant (P < 0.001) increases in glucose (9.4 ± 13.1%), insulin (70.2 ± 91.0%), HOMA-IR (87.8 ± 103.9%), and adiponectin (169.3 ± 111.6%). The increase in adiponectin was significantly associated with increase in glucose (r = 0.221, P < 0.05), insulin (r = 0.184, P < 0.05), and HOMA-IR (r = 0.237, P < 0.01) and the association remained significant after adjustment for changes in body weight or body fat mass. Conclusion. Treatment with ER niacin/laropiprant led to a significant increase in adiponectin levels but worsening of glucose levels and insulin resistance, and the increase in adiponectin and insulin resistance were correlated suggesting the increase in adiponectin did not ameliorate the deterioration in insulin resistance. Clinical trial is registered with number on WHO-ICTRP: ChiCTR-ONC-10001038. PMID:26063948

  19. Peroxisome proliferator-activated receptor γ enhances adiponectin secretion via up-regulating DsbA-L expression.

    PubMed

    Jin, Dan; Sun, Jun; Huang, Jing; Yu, Xiaoling; Yu, An; He, Yiduo; Li, Qiang; Yang, Zaiqing

    2015-08-15

    Disulfide-bond A oxidoreductase like-protein (DsbA-L) was identified as a molecular chaperone facilitating the assembly and secretion of adiponectin, an adipokine with multiple beneficial effects. In obesity the level of DsbA-L is reduced with a concomitant decrease of the circulating adiponectin level, especially of the high molecular weight form (HMW). Both rodent and human studies have shown that the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-γ agonists increase adiponectin levels in serum by activating PPARγ, which up-regulates critical endoplasmic reticulum (ER) chaperones thus facilitating protein folding. As shown in the present study, overexpression of PPARγ in human embryonic kidney (HEK) 293 cells elicited the cellular release of HMW adiponectin. PPARγ enhanced expression of DsbA-L by binding directly to peroxisome proliferator response element (PPRE) site within the DsbA-L promoter. Conversely, in differentiated 3T3-L1 cells, PPARγ knockdown resulted in decreased expression of Adiponectin, DsbA-L and ERp44. DsbA-L expression increased after PPARγ agonist treatment and decreased upon treatment with PPARγ antagonist in 3T3-L1 adipocytes. DsbA-L deficiency in differentiated 3T3-L1 cells impaired the secretion of adiponectin. We therefore propose that DsbA-L plays an important role in facilitating HMW adiponectin formation and release from cells under the regulation of PPARγ.

  20. Association of Plasma Adiponectin and Oxidized Low-Density Lipoprotein with Carotid Intima-Media Thickness in Diabetic Nephropathy

    PubMed Central

    Georgoulidou, Anastasia; Roumeliotis, Athanasios; Roumeliotis, Stefanos; Giannakopoulou, Efstathia; Papanas, Nikolaos; Passadakis, Ploumis; Manolopoulos, Vangelis G.; Vargemezis, Vassilis

    2015-01-01

    Aims. We sought to determine the association between levels of adiponectin and oxidized low-density lipoprotein (ox-LDL) in patients with diabetic nephropathy as well as their effect on carotid intima-media thickness (cIMT). Methods. Adiponectin and ox-LDL were determined in 25 diabetic patients without nephropathy and 94 patients at different stages of diabetic nephropathy including subjects on hemodialysis. cIMT was measured using real-time B-mode ultrasonography. Results. Plasma adiponectin levels increased significantly with severity of diabetic nephropathy (P = 0.002), on the contrary to ox-LDL which decreased with disease severity (P < 0.001). cIMT was significantly higher at late stages of diabetic nephropathy compared with early stages (P = 0.022). Adiponectin was a significant negative predictor of ox-LDL levels (β = −5.45, P = 0.023), independently of confounding factors. There was no significant correlation between cIMT and adiponectin or ox-LDL either in the total sample population or according to disease staging. Cluster analysis showed that patients with the highest cIMT values, highest levels of adiponectin, and lowest levels of ox-LDL were included in one cluster and all assigned to stage 5 of diabetic nephropathy. Conclusions. There was no significant association between adiponectin or ox-LDL and cIMT and, therefore, other factors affecting this surrogate marker of cardiovascular disease in diabetic nephropathy should be sought. PMID:26064982

  1. Adiponectin and the mediation of HDL cholesterol change with improved lifestyle: The Look AHEAD Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adipose tissue dysfunction plays a key role in the development of the metabolic abnormalities characteristic of type 2 diabetes (T2DM) and participates actively in lipid metabolism. Adiponectin, found abundantly in circulation and a marker of adipose health, is decreased in obese persons with T2DM. ...

  2. Serum adiponectin and leptin concentrations in HIV-infected children with fat redistribution syndrome.

    PubMed

    Verkauskiene, Rasa; Dollfus, Catherine; Levine, Martine; Faye, Albert; Deghmoun, Samia; Houang, Muriel; Chevenne, Didier; Bresson, Jean-Louis; Blanche, Stéphane; Lévy-Marchal, Claire

    2006-08-01

    Human immunodeficiency virus (HIV)-related lipodystrophy is characterized by adipose tissue redistribution, dyslipidemia, and insulin resistance. We hypothesized that fat redistribution and metabolic abnormalities in HIV-infected children are related to alterations in endocrine function of adipose tissue. A multicenter study was conducted in 130 HIV-infected children. Lipodystrophy definition was based on the central to peripheral skinfold ratio. Fasting adiponectin, leptin, insulin concentrations, glycemia, and lipid profile were measured in all children. Fat redistribution syndrome was apparent in 32 children: 14 with atrophic (LPDA) and 18 with hypertrophic lipodystrophy (LPDH). Mean serum adiponectin levels were significantly decreased in LPDA and LPDH groups compared with the group with no lipodystrophy (LPD-). Fasting insulin concentration was significantly higher in LPDA and LPDH groups versus LPD-. Mean serum leptin concentration was significantly increased only in LPDH compared with LPDA and LPD- groups. Triglyceride levels were significantly increased and high-density lipoprotein (HDL)-cholesterol concentration decreased in the LPDA versus LPD- group. Controlling for puberty stage, gender, percentage of total fat mass, serum lipids, HIV treatment, and disease severity, adiponectin was significantly and inversely associated with central obesity and insulin/glucose ratio. Fat redistribution had no significant effect on leptin concentration, which was directly related to the percentage of body fat, female gender, and insulin/glucose ratio. In conclusion, HIV-infected children with symptoms of fat redistribution have decreased levels of adiponectin, associated with insulin resistance and dyslipidemia.

  3. Evaluation of body weight, insulin resistance, leptin and adiponectin levels in premenopausal women with hyperprolactinemia.

    PubMed

    Atmaca, Aysegul; Bilgici, Birsen; Ecemis, Gulcin Cengiz; Tuncel, Ozgur Korhan

    2013-12-01

    The effects of hyperprolactinemia on metabolic parameters are not clear and a few data evaluating adiponectin levels in prolactinoma and idiopathic hyperprolactinemia exist. The aim of this study was to evaluate the effects of hyperprolactinemia on body weight, insulin resistance, beta cell function, and leptin and adiponectin levels in premenopausal women with hyperprolactinemia. Forty premenopausal women with prolactinoma or idiopathic hyperprolactinemia were compared to 41 age-matched healthy premenopausal women with regard to body weight, body mass index, waist and hip circumferences, waist to hip ratio, fasting plasma glucose, insulin levels, insulin resistance measured by homeostasis model assessment (HOMA)-insulin resistance index, beta cell function measured by HOMA-β index, leptin and adiponectin levels. Plasma insulin levels and HOMA indexes (both insulin resistance and beta indexes) were significantly higher in hyperprolactinemic women. The other parameters were similar between both groups. There was a positive correlation between prolactin levels and fasting plasma glucose in hyperprolactinemic women. The results of this study showed that high prolactin levels may be associated with hyperinsulinemia and insulin resistance in premenopausal women. This effect seems to be independent of body weight, leptin and adiponectin levels. High prolactin levels may directly stimulate insulin secretion from pancreas and directly cause hepatic and whole-body insulin resistance.

  4. Osmotin: a plant sentinel and a possible agonist of mammalian adiponectin

    PubMed Central

    Anil Kumar, S.; Hima Kumari, P.; Shravan Kumar, G.; Mohanalatha, C.; Kavi Kishor, P. B.

    2015-01-01

    Osmotin is a stress responsive antifungal protein belonging to the pathogenesis-related (PR)-5 family that confers tolerance to both biotic and abiotic stresses in plants. Protective efforts of osmotin in plants range from high temperature to cold and salt to drought. It lyses the plasma membrane of the pathogens. It is widely distributed in fruits and vegetables. It is a differentially expressed and developmentally regulated protein that protects the cells from osmotic stress and invading pathogens as well, by structural or metabolic alterations. During stress conditions, osmotin helps in the accumulation of the osmolyte proline, which quenches reactive oxygen species and free radicals. Osmotin expression results in the accumulation of storage reserves and increases the shelf-life of fruits. It binds to a seven-transmembrane-domain receptor-like protein and induces programmed cell death in Saccharomyces cerevisiae through RAS2/cAMP signaling pathway. Adiponectin, produced in adipose tissues of mammals, is an insulin-sensitizing hormone. Strangely, osmotin acts like the mammalian hormone adiponectin in various in vitro and in vivo models. Adiponectin and osmotin, the two receptor binding proteins do not share sequence similarity at the amino acid level, but interestingly they have a similar structural and functional properties. In experimental mice, adiponectin inhibits endothelial cell proliferation and migration, primary tumor growth, and reduces atherosclerosis. This retrospective work examines the vital role of osmotin in plant defense and as a potential targeted therapeutic drug for humans. PMID:25852715

  5. The Balance between Leptin and Adiponectin in the Control of Carcinogenesis- Focus on Mammary Tumorigenesis

    PubMed Central

    Grossmann, Michael E.

    2013-01-01

    A number of studies indicate that a growing list of cancers may be influenced by obesity. In obese individuals these cancers can be more frequent and more aggressive resulting in reduced survival. One of the most prominent and well characterized cancers in this regard is breast cancer. Obesity plays a complex role in breast cancer and is associated with increased inflammation, angiogenesis and alterations in serum levels of potential growth factors such as adiponectin, leptin and estrogen in the serum. Reduced levels of serum adiponectin have been reported in breast cancer patients compared to healthy controls, particularly in postmenopausal women. The role of serum leptin levels in breast cancer appears to be more complex. Some studies have shown leptin to be increased in women with breast cancer but other studies have found leptin to be decreased or unchanged. This may be due to a number of confounding issues. We and others propose that it may be the levels of adiponectin and leptin as well as the balance of adiponectin and leptin that are the critical factors in breast and other obesity related cancer tumorigenesis. PMID:22728769

  6. Does Dietary Iodine Regulate Oxidative Stress and Adiponectin Levels in Human Breast Milk?

    PubMed Central

    Gutiérrez-Repiso, Carolina; Velasco, Inés; Garcia-Escobar, Eva; Garcia-Serrano, Sara; Rodríguez-Pacheco, Francisca; Linares, Francisca; Ruiz de Adana, Maria Soledad; Rubio-Martin, Elehazara; Garrido-Sanchez, Lourdes; Cobos-Bravo, Juan Francisco; Priego-Puga, Tatiana; Rojo-Martinez, Gemma; Soriguer, Federico

    2014-01-01

    Abstract Little is known about the association between iodine and human milk composition. In this study, we investigated the association between iodine and different markers of oxidative stress and obesity-related hormones in human breast milk. This work is composed of two cross-sectional studies (in lactating women and in the general population), one prospective and one in vitro. In the cross-sectional study in lactating women, the breast milk iodine correlated negatively with superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) activities, and with adiponectin levels. An in vitro culture of human adipocytes with 1 μM potassium iodide (KI, dose similar to the human breast milk iodine concentration) produced a significant decrease in adiponectin, GSH-Px, SOD1, and SOD2 mRNA expression. However, after 2 months of treatment with KI in the prospective study, a positive correlation was found between 24-h urinary iodine and serum adiponectin. Our observations lead to the hypothesis that iodine may be a factor directly involved in the regulation of oxidative stress and adiponectin levels in human breast milk. Antioxid. Redox Signal. 20, 847–853. PMID:24001137

  7. Globular adiponectin improves high glucose-suppressed endothelial progenitor cell function through endothelial nitric oxide synthase dependent mechanisms.

    PubMed

    Huang, Po-Hsun; Chen, Jia-Shiong; Tsai, Hsiao-Ya; Chen, Yung-Hsiang; Lin, Feng-Yen; Leu, Hsin-Bang; Wu, Tao-Cheng; Lin, Shing-Jong; Chen, Jaw-Wen

    2011-07-01

    Plasma levels of adiponectin, an adipose-specific protein with putative anti-atherogenic properties, could be down-regulated in obese and diabetic subjects. Recent insights suggest that the injured endothelial monolayer is regenerated by circulating endothelial progenitor cells (EPCs), but high glucose reduces number and functions of EPCs. Here, we tested the hypothesis that globular adiponectin can improve high glucose-suppressed EPC functions by restoration of endothelial nitric oxide synthase (eNOS) activity. Late EPCs isolated from healthy subjects appeared with cobblestone shape at 2-4 weeks. EPCs were incubated with high glucose (25 mM) and treatment with globular adiponectin for functional study. Migration and tube formation assays were used to evaluate the vasculogenetic capacity of EPCs. The activities of eNOS, Akt and concentrations of nitric oxide (NO) were also determined. Administration of globular adiponectin at physiological concentrations promoted EPC migration and tube formation, and dose-dependently upregulated phosphorylation of eNOS, Akt and augmented NO production. Chronic incubation of EPCs in high-glucose medium significantly impaired EPC function and induced cellular senescence, but these suppression effects were reversed by treatment with globular adiponectin. Globular adiponectin reversed high glucose-impaired EPC functions through NO- and p38 MAPK-related mechanisms. In addition, nude mice that received EPCs treated with adiponectin in high glucose medium showed a significant improvement in blood flow than those received normal saline and EPCs incubated in high glucose conditions. The administration of globular adiponectin improved high glucose-impaired EPC functions in vasculogenesis by restoration of eNOS activity. These beneficial effects may provide some novel rational to the vascular protective properties of adiponectin.

  8. The Role of Adiponectin in Breast Cancer: A Meta-Analysis

    PubMed Central

    Liu, Li-Yuan; Wang, Meng; Ma, Zhong-Bing; Yu, Li-Xiang; Zhang, Qiang; Gao, De-Zong; Wang, Fei; Yu, Zhi-Gang

    2013-01-01

    Published results suggests that high adiponectin level may decrease the risk of breast cancer. However, available evidence on breast cancer is conflicting. Therefore a meta-analysis was performed to assess the association between blood adiponectin and breast cancer risk. PubMed database, Web of Science, Elsevier Science, Springer Link and bibliographies of retrieved articles were searched for epidemiological studies published up to March 2013. Meta-analysis was performed on the combined effect values (OR) as well as standardized mean difference (SMD) including 17 studies. Fixed or random effect pooled measure was selected on the basis of homogeneity test among studies. The publication bias was assessed by the Egger’s regression asymmetry test and Begg’s rank correlation test with Begg’s funnel plot. Subgroup analyses and sensitivity analysis were also performed. A total of 13 studies involving 3578 breast cancer cases and 4363 controls contributed to the OR analysis. The high adiponectin level did not significantly affect breast cancer risk (OR=0.902, 95% CI=0.773–1.053). After excluding articles that were the key contributors to between-study heterogeneity, the OR of high adiponectin level was associated with decreased breast cancer risk (OR=0.838, 95% CI=0.744–0.943). There was a significantly association between high adiponectin level and postmenopausal breast cancer women (OR=0.752, 95%CI=0.604-0.936); and it was not associated with premenopausal breast cancer women (OR=0.895, 95%CI=0.638-1.256). The result of pooled measure on SMD was that the high adiponectin level was associated with decreased breast cancer risk (SMD= -0.348, 95% CI= -0.533--0.614) after excluding articles which were the key contributors to between-study heterogeneity. Our findings indicate that high adiponectin level might decrease the risk of postmenopausal breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with

  9. Phycocyanin prevents hypertension and low serum adiponectin level in a rat model of metabolic syndrome.

    PubMed

    Ichimura, Mayuko; Kato, Shigeko; Tsuneyama, Koichi; Matsutake, Sachiko; Kamogawa, Mai; Hirao, Eri; Miyata, Ayako; Mori, Sawako; Yamaguchi, Noriaki; Suruga, Kazuhito; Omagari, Katsuhisa

    2013-05-01

    Endothelial dysfunction is associated with hypertension, atherosclerosis, and metabolic syndrome. Phycocyanin is a pigment found in the blue-green algae, Spirulina, which possesses antihypertensive effect. In this study, we hypothesized that phycocyanin derived from Spirulina exerts antihypertensive actions by improving endothelial dysfunction in metabolic syndrome. Spontaneously hypertensive/NIH-corpulent (SHR/NDmcr-cp) rats were divided into 4 groups then fed a normal diet with or without phycocyanin (2500-, 5000-, or 10,000-mg/kg diet) for 25 weeks. At 34 weeks of age, although systolic blood pressure was not significantly different among groups, phycocyanin-fed groups exhibited a dose-dependent decrease in blood pressure. Serum levels of adiponectin and messenger RNA levels of adiponectin and CCAAT/enhancer-binding protein α in the adipose tissue of rats fed diets containing phycocyanin tended to be higher than those of rats fed a normal diet, but the differences were not statistically significant. Immunohistochemistry analysis showed a significant and positive correlation between aortic endothelial nitric oxide synthase (eNOS) expression levels, a downstream target of the adiponectin receptor, and serum adiponectin levels, although there were no significant differences in eNOS expression among groups. There was also no significant correlation between eNOS expression levels and systolic blood pressure. These results suggest that long-term administration of phycocyanin may ameliorate systemic blood pressure by enhancing eNOS expression in aorta that is stimulated by adiponectin. Phycocyanin may be beneficial for preventing endothelial dysfunction-related diseases in metabolic syndrome.

  10. Direct effects of leptin and adiponectin on peripheral reproductive tissues: a critical review

    PubMed Central

    Kawwass, Jennifer F.; Summer, Ross; Kallen, Caleb B.

    2015-01-01

    Obesity is a risk factor for infertility and adverse reproductive outcomes. Adipose tissue is an important endocrine gland that secretes a host of endocrine factors, called adipokines, which modulate diverse physiologic processes including appetite, metabolism, cardiovascular function, immunity and reproduction. Altered adipokine expression in obese individuals has been implicated in the pathogenesis of a host of health disorders including diabetes and cardiovascular disease. It remains unclear whether adipokines play a significant role in the pathogenesis of adverse reproductive outcomes in obese individuals and, if so, whether the adipokines are acting directly or indirectly on the peripheral reproductive tissues. Many groups have demonstrated that receptors for the adipokines leptin and adiponectin are expressed in peripheral reproductive tissues and that these adipokines are likely, therefore, to exert direct effects on these tissues. Many groups have tested for direct effects of leptin and adiponectin on reproductive tissues including the testis, ovary, uterus, placenta and egg/embryo. The hypothesis that decreased fertility potential or adverse reproductive outcomes may result, at least in part, from defects in adipokine signaling within reproductive tissues has also been tested. Here, we present a critical analysis of published studies with respect to two adipokines, leptin and adiponectin, for which significant data have been generated. Our evaluation reveals significant inconsistencies and methodological limitations regarding the direct effects of these adipokines on peripheral reproductive tissues. We also observe a pervasive failure to account for in vivo data that challenge observations made in vitro. Overall, while leptin and adiponectin may directly modulate peripheral reproductive tissues, existing data suggest that these effects are minor and non-essential to human or mouse reproductive function. Current evidence suggests that direct effects of

  11. Adiponectin is Protective against Oxidative Stress Induced Cytotoxicity in Amyloid-Beta Neurotoxicity

    PubMed Central

    Chan, Koon-Ho; Lam, Karen Siu-Ling; Cheng, On-Yin; Kwan, Jason Shing-Cheong; Ho, Philip Wing-Lok; Cheng, Kenneth King-Yip; Chung, Sookja Kim; Ho, Jessica Wing-Man; Guo, Vivian Yawei; Xu, Almin

    2012-01-01

    Beta-amyloid (Aβ ) neurotoxicity is important in Alzheimer’s disease (AD) pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes (T2DM) which is characterized by insulin resistance. Interestingly, T2DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance). We studied the potential protective effect of adiponectin (an adipokine with insulin-sensitizing, anti-inflammatory and anti-oxidant properties) against Aβ neurotoxicity in human neuroblastoma cells (SH-SY5Y) transfected with the Swedish amyloid precursor protein (Sw-APP) mutant, which overproduced Aβ with abnormal intracellular Aβ accumulation. Cytotoxicity was measured by assay for lactate dehydrogenase (LDH) released upon cell death and lysis. Our results revealed that Sw-APP transfected SH-SY5Y cells expressed both adiponectin receptor 1 and 2, and had increased AMP-activated protein kinase (AMPK) activation and enhanced nuclear factor-kappa B (NF-κB) activation compared to control empty-vector transfected SH-SY5Y cells. Importantly, adiponectin at physiological concentration of 10 µg/ml protected Sw-APP transfected SH-SY5Y cells against cytotoxicity under oxidative stress induced by hydrogen peroxide. This neuroprotective action of adiponectin against Aβ neurotoxicity-induced cytotoxicity under oxidative stress involved 1) AMPK activation mediated via the endosomal adaptor protein APPL1 (adaptor protein with phosphotyrosine binding, pleckstrin homology domains and leucine zipper motif) and possibly 2) suppression of NF-κB activation. This raises the possibility of novel therapies for AD such as adiponectin receptor agonists. PMID:23300647

  12. Fenofibrate administration to arthritic rats increases adiponectin and leptin and prevents oxidative muscle wasting

    PubMed Central

    Castillero, Estíbaliz; Martín, Ana Isabel; Nieto-Bona, Maria Paz; Fernández-Galaz, Carmen; López-Menduiña, María; Villanúa, María Ángeles; López-Calderón, Asunción

    2012-01-01

    Chronic inflammation induces skeletal muscle wasting and cachexia. In arthritic rats, fenofibrate, a peroxisome proliferator-activated receptor α (PPARα (PPARA)) agonist, reduces wasting of gastrocnemius, a predominantly glycolytic muscle, by decreasing atrogenes and myostatin. Considering that fenofibrate increases fatty acid oxidation, the aim of this study was to elucidate whether fenofibrate is able to prevent the effect of arthritis on serum adipokines and on soleus, a type I muscle in which oxidative metabolism is the dominant source of energy. Arthritis was induced by injection of Freund's adjuvant. Four days after the injection, control and arthritic rats were gavaged daily with fenofibrate (300 mg/kg bw) or vehicle over 12 days. Arthritis decreased serum leptin, adiponectin, and insulin (P<0.01) but not resistin levels. In arthritic rats, fenofibrate administration increased serum concentrations of leptin and adiponectin. Arthritis decreased soleus weight, cross-sectional area, fiber size, and its Ppar α mRNA expression. In arthritic rats, fenofibrate increased soleus weight, fiber size, and Ppar α expression and prevented the increase in Murf1 mRNA. Fenofibrate decreased myostatin, whereas it increased MyoD (Myod1) and myogenin expressions in the soleus of control and arthritic rats. These data suggest that in oxidative muscle, fenofibrate treatment is able to prevent arthritis-induced muscle wasting by decreasing Murf1 and myostatin expression and also by increasing the myogenic regulatory factors, MyoD and myogenin. Taking into account the beneficial action of adiponectin on muscle wasting and the correlation between adiponectin and soleus mass, part of the anticachectic action of fenofibrate may be mediated through stimulation of adiponectin secretion. PMID:23781298

  13. Effects of radioiodine administration on serum concentrations of matrix metalloproteinases, adiponectin and thrombospondin-1

    PubMed Central

    2013-01-01

    Background In order to assess safety of radioactive iodine administration in the treatment of thyrotoxicosis, we measured concentrations of matrix metalloproteinase-2 (MMP-2), its main inhibitor – TIMP-2 (tissue inhibitor of MMP-2), matrix metalloproteinase-9 (MMP-9), its main inhibitor – TIMP-1, adiponectin, as well as pro-inflammatory and procancerogenic thrombospondin-1 (TSP-1). Design and patients The study involved 23 patients treated with radioiodine for thyrotoxicosis. Serum concentrations of TSH, free T4, free T3, MMP-2, MMP-9, TIMP-1, TIMP-2, total adiponectin and TSP-1 were measured by immunoassays just before radioiodine administration (visit 1), and subsequently, after 7 days (visit 2), 3 months (visit 3), 6 to 8 months (visit 4) and 15–18 months after radioiodine administration (visit 5). Results There were no acute changes in serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, adiponectin and TSP-1 (visit 1 vs. 2). Subsequently, there was an increase in MMP-2 (from 393±106 ng/ml to 774±424 ng/ml), TIMP-1 (from 177±76 ng/ml to 296±118 ng/ml), and adiponectin (from 16442±9490 ng/ml to 23518±9840 ng/ml), visit 1 to 5, respectively (p < 0.01). Further analysis revealed no significant change in MMP-2/TIMP-2 ratio, but there was a significant decrease in MMP-9/TIMP-1 ratio (p < 0.05), suggestive of possible decrease in free MMP-9 concentrations. Conclusions Our data reveal a significant and sustained increase in serum adiponectin, as well as possible decrease of free MMP-9 concentration after radioiodine administration. In contrast, there was no significant change of TSP-1. This might indicate overall safety of radioiodine treatment of thyrotoxicosis in terms of the risks of subsequent cardiovascular and neoplastic disease. PMID:23919647

  14. Effects of sugar-sweetened beverages on plasma acylation stimulating protein, leptin, and adiponectin: Relationships with metabolic outcomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE: The effects of fructose and glucose consumption on plasma acylation stimulating protein (ASP), adiponectin, and leptin concentrations relative to energy intake, body weight, adiposity, circulating triglycerides, and insulin sensitivity were determined. DESIGN AND METHODS: Thirty two over...

  15. Effects of isotretinoin on body mass index, serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients

    PubMed Central

    Ayvaz, Havva Hilal; Ozturk, Gulfer; Ergin, Can; Akıs, Havva Kaya; Gonul, Muzeyyen; Arzuhal, Ercan

    2016-01-01

    Introduction Isotretinoin has been successfully used for the treatment of acne vulgaris. Aim To investigate the effects of isotretinoin on body mass index (BMI), to determine whether isotretinoin causes any changes in serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients, and to correlate variables. Material and methods Thirty-two patients were included in this study. Oral isotretinoin was begun at a dose of 0.5–0.6 mg/kg and raised to 0.6–0.75 mg/kg. Pretreatment and posttreatment third-month BMI and adiponectin, leptin, and ghrelin serum levels were measured. Results The pre- and posttreatment BMI values were not significantly different. In addition, serum adiponectin and leptin levels were significantly increased following isotretinoin therapy while serum ghrelin levels were not different. Conclusions Isotretinoin may exert its anti-inflammatory activity by increasing leptin and adiponectin levels. PMID:27605902

  16. Correlation of Adiponectin mRNA Abundance and Its Receptors with Quantitative Parameters of Sperm Motility in Rams

    PubMed Central

    Kadivar, Ali; Heidari Khoei, Heidar; Hassanpour, Hossein; Golestanfar, Arefe; Ghanaei, Hamid

    2016-01-01

    Background Adiponectin and its receptors (AdipoR1 and AdipoR2), known as adiponectin system, have some proven roles in the fat and glucose metabolisms. Several studies have shown that adiponectin can be considered as a candidate in linking metabolism to testicular function. In this regard, we evaluated the correlation between sperm mRNA abundance of adiponectin and its receptors, with sperm motility indices in the present study. Materials and Methods In this completely randomized design study, semen samples from 6 adult rams were fractionated on a two layer discontinuous percoll gradient into high and low motile sperm cells, then quantitative parameters of sperm motility were determined by computer-assisted sperm analyzer (CASA). The mRNA abundance levels of Adiponectin, AdipoR1 and AdipoR2 were measured quantitatively using real-time reverse transcriptase polymerase chain reaction (qRT-PCR) in the high and low motile groups. Results Firstly, we showed that adiponectin and its receptors (AdipoR1 and AdipoR2) were transcriptionally expressed in the ram sperm cells. Using Pfaff based method qRT- PCR, these levels of transcription were significantly higher in the high motile rather than low motile samples. This increase was 3.5, 3.6 and 2.5 fold change rate for Adiponectin, AdipoR1 and AdipoR2, respectively. Some of sperm motility indices [curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP), linearity (LIN), wobble (WOB) and straightness (STR)] were also significantly correlated with Adiponectin and AdipoR1 relative expression. The correlation of AdipoR2 was also significant with the mentioned parameters, although this correlation was not comparable with adiponectin and AdipoR1. Conclusion This study revealed the novel association of adiponectin system with sperm motility. The results of our study suggested that adiponectin is one of the possible factors which can be evaluated and studied in male infertility disorders. PMID:27123210

  17. Adiponectin levels predict prediabetes risk: the Pathobiology of Prediabetes in A Biracial Cohort (POP-ABC) study

    PubMed Central

    Jiang, Yunna; Owei, Ibiye; Wan, Jim; Ebenibo, Sotonte; Dagogo-Jack, Samuel

    2016-01-01

    Background Adiponectin levels display ethnic disparities, and are inversely associated with the risk of type 2 diabetes (T2DM). However, the association of adiponectin with prediabetes risk in diverse populations has not been well-studied. Here, we assessed baseline adiponectin levels in relation to incident prediabetes in a longitudinal biracial cohort. Research design and methods The Pathobiology of Prediabetes in A Biracial Cohort study followed non-diabetic offspring of parents with T2DM for the occurrence of prediabetes, defined as impaired fasting glucose and/or impaired glucose tolerance. Assessments at enrollment and during follow-up included a 75 g oral glucose tolerance test, anthropometry, biochemistries (including fasting insulin and adiponectin levels), insulin sensitivity and insulin secretion. Logistic regression was used to evaluate the contribution of adiponectin to risk of progression to prediabetes. Results Among the 333 study participants (mean (SD) age 44.2 (10.6) year), 151(45.3%) were white and 182 (54.8%) were black. During approximately 5.5 (mean 2.62) years of follow-up, 110 participants (33%) progressed to prediabetes (N=100) or T2DM (N=10), and 223 participants (67%) were non-progressors. The mean cohort adiponectin level was 9.41+5.30 μg/mL (range 3.1–45.8 μg/mL); values were higher in women than men (10.3+5.67 μg/mL vs 7.27+3.41 μg/mL, p<0.0001) and in white than black offspring (10.7+5.44 μg/mL vs 8.34+4.95 μg/mL, p<0.0001). Adiponectin levels correlated inversely with adiposity and glycemia, and positively with insulin sensitivity and high-density lipoprotein cholesterol levels. Baseline adiponectin strongly predicted incident prediabetes: the HR for prediabetes per 1 SD (approximately 5 μg/mL) higher baseline adiponectin was 0.48 (95% CI 0.27 to 0.86, p=0.013). Conclusions Among healthy white and black adults with parental history of T2DM, adiponectin level is a powerful risk marker of incident prediabetes

  18. FTO rs 9939609 SNP Is Associated With Adiponectin and Leptin Levels and the Risk of Obesity in a Cohort of Romanian Children Population

    PubMed Central

    Duicu, Carmen; Mărginean, Cristina Oana; Voidăzan, Septimiu; Tripon, Florin; Bănescu, Claudia

    2016-01-01

    Abstract Obesity is a disorder with increasing frequency in children and adolescents, directly linked with various diseases. Variants in the FTO (fat mass and obesity-related) gene have been associated with body mass index and waist and hip circumferences in widespread populations. The aim of this case-control study was to assess if there is any association between FTO gene variants rs9939609, respectively, rs17817449 with anthropometric and metabolic biomarkers (fasting glucose, TC, HDL-cholesterol, LDL-cholesterol, triglycerides) and adipokines (adiponectin and leptin), in Romanian obese children. A total of 387 children, 201 obese and 186 nonobese individuals, were included in this prospective study. Genotyping of the FTO gene polymorphisms for all subjects was performed using the restriction fragment length polymorphism (PCR–RFLP) method. Significant associations were found between FTO rs9939609 single nucleotide polymorphism (SNP) and obesity. AA genotype carriers have a 2.02 times higher risk for obesity compared with AT+TT genotype carriers. Risk allele carriers of rs17817449 SNP had somewhat higher values of weight, body mass index, waist and hip circumference, total cholesterol, triglycerides, adiponectin, and fasting glucose. This study revealed the genetic association between rs9939609 SNP of FTO and obesity in a Romanian population, and to the authors’ knowledge, this is the first study to investigate this association in a Romanian population. This study also established that combined variant genotypes (AA/GG) of FTO rs9939609 /rs17817449 are strongly associated with several measures of adiposity (weight, BMI-SD, mid-upper arm circumference, tricipital skinfold thicknesses) and are also associated with total cholesterol, triglyceride, and LDL-cholesterol levels. PMID:27196486

  19. FTO rs 9939609 SNP Is Associated With Adiponectin and Leptin Levels and the Risk of Obesity in a Cohort of Romanian Children Population.

    PubMed

    Duicu, Carmen; Mărginean, Cristina Oana; Voidăzan, Septimiu; Tripon, Florin; Bănescu, Claudia

    2016-05-01

    Obesity is a disorder with increasing frequency in children and adolescents, directly linked with various diseases. Variants in the FTO (fat mass and obesity-related) gene have been associated with body mass index and waist and hip circumferences in widespread populations.The aim of this case-control study was to assess if there is any association between FTO gene variants rs9939609, respectively, rs17817449 with anthropometric and metabolic biomarkers (fasting glucose, TC, HDL-cholesterol, LDL-cholesterol, triglycerides) and adipokines (adiponectin and leptin), in Romanian obese children.A total of 387 children, 201 obese and 186 nonobese individuals, were included in this prospective study. Genotyping of the FTO gene polymorphisms for all subjects was performed using the restriction fragment length polymorphism (PCR-RFLP) method.Significant associations were found between FTO rs9939609 single nucleotide polymorphism (SNP) and obesity. AA genotype carriers have a 2.02 times higher risk for obesity compared with AT+TT genotype carriers. Risk allele carriers of rs17817449 SNP had somewhat higher values of weight, body mass index, waist and hip circumference, total cholesterol, triglycerides, adiponectin, and fasting glucose.This study revealed the genetic association between rs9939609 SNP of FTO and obesity in a Romanian population, and to the authors' knowledge, this is the first study to investigate this association in a Romanian population. This study also established that combined variant genotypes (AA/GG) of FTO rs9939609 /rs17817449 are strongly associated with several measures of adiposity (weight, BMI-SD, mid-upper arm circumference, tricipital skinfold thicknesses) and are also associated with total cholesterol, triglyceride, and LDL-cholesterol levels.

  20. Activation of autophagy by globular adiponectin attenuates ethanol-induced apoptosis in HepG2 cells: involvement of AMPK/FoxO3A axis.

    PubMed

    Nepal, Saroj; Park, Pil-Hoon

    2013-10-01

    Hepatocellular apoptosis is an important pathological entity of alcoholic liver disease. Previously, we have shown that globular adiponectin (gAcrp) protects liver cells from ethanol-induced apoptosis by modulating an array of signaling pathways. In the present study, we investigated the role of autophagy induction by gAcrp in the suppression of ethanol-induced apoptosis and its potential mechanism(s) in liver cells. Here, we demonstrated that gAcrp significantly restores ethanol-induced suppression of autophagy-related genes, including Beclin-1 and microtubule-associated protein light chain (LC3B) both in primary rat hepatocytes and human hepatoma cell line (HepG2). Globular adiponectin also restored autophagosome formation suppressed by ethanol treatment in HepG2. Furthermore, inhibition of gAcrp-induced autophagic process by knock-down of LC3B prevented protection from ethanol-induced apoptosis. In particular, the autophagic process induced by gAcrp was involved in the suppression of ethanol-induced activation of caspase-8 and expression of Bax. Moreover, knock-down of AMPK by small interfering RNA (siRNA) blocked gAcrp-induced expression of genes related to autophagy, which in turn prevented protection from ethanol-induced apoptosis, suggesting that AMPK plays an important role in the induction of autophagy and protection of liver cells by gAcrp. Finally, we also showed that gAcrp treatment induces translocation of the forkhead box O member protein, FoxO3A, into the nucleus, which may play a role in the induction of autophagy-related genes. Taken together, our data demonstrated that gAcrp protects liver cells from ethanol-induced apoptosis via induction of autophagy. Further, the AMPK-FoxO3A axis plays a cardinal role in gAcrp-induced autophagy and subsequent inhibition of ethanol-induced apoptosis.

  1. Progestin and AdipoQ Receptor 7, Progesterone Membrane Receptor Component 1 (PGRMC1), and PGRMC2 and Their Role in Regulating Progesterone's Ability to Suppress Human Granulosa/Luteal Cells from Entering into the Cell Cycle.

    PubMed

    Sueldo, Carolina; Liu, Xiufang; Peluso, John J

    2015-09-01

    The present studies were designed to determine the role of progesterone receptor membrane component 1 (PGRMC1), PGRMC2, progestin and adipoQ receptor 7 (PAQR7), and progesterone receptor (PGR) in mediating the antimitotic action of progesterone (P4) in human granulosa/luteal cells. For these studies granulosa/luteal cells of 10 women undergoing controlled ovarian hyperstimulation were isolated, maintained in culture, and depleted of PGRMC1, PGRMC2, PAQR7, or PGR by siRNA treatment. The rate of entry into the cell cycle was assessed using the FUCCI cell cycle sensor to determine the percentage of cells in the G1/S stage of the cell cycle. PGRMC1, PGRMC2, PAQR7, and PGR mRNA levels were assessed by real-time PCR and their interactions monitored by in situ proximity ligation assays (PLAs). These studies revealed that PGRMC1, PGRMC2, PAQR7, and PGR were expressed by granulosa/luteal cells from all patients, with PGRMC1 mRNA being most abundant, followed by PAQR7, PGRMC2, and PGR. However, their mRNA levels showed considerable patient variation. P4's ability to suppress entry into the cell cycle was dependent on PGRMC1, PGRMC2, and PAQR7 but not PGR. Moreover, PLAs indicated that PGRMC1, PGRMC2, and PAQR7 formed a complex within the cytoplasm. Based on these studies, it is proposed that these three P4 mediators form a complex within the cytoplasm that is required for P4's action. Moreover, P4's ability to regulate human follicle development may be dependent in part on the expression levels of each of these P4 mediators.

  2. High serum adiponectin predicts incident fractures in elderly men: Osteoporotic fractures in men (MrOS) Sweden.

    PubMed

    Johansson, Helena; Odén, Anders; Lerner, Ulf H; Jutberger, Hans; Lorentzon, Mattias; Barrett-Connor, Elizabeth; Karlsson, Magnus K; Ljunggren, Osten; Smith, Ulf; McCloskey, Eugene; Kanis, John A; Ohlsson, Claes; Mellström, Dan

    2012-06-01

    Adipocytes and osteoblasts share a common progenitor, and there is, therefore, potential for both autocrine and endocrine effects of adiponectin on skeletal metabolism. The aim of the present study was to determine whether high serum adiponectin was associated with an increased risk of fracture in elderly men. We studied the relationship between serum adiponectin and the risk of fracture in 999 elderly men drawn from the general population and recruited to the Osteoporotic Fractures in Men (MrOS) study in Gothenburg, Sweden. Baseline data included general health questionnaires, lifestyle questionnaires, body mass index (BMI), bone mineral density (BMD), serum adiponectin, osteocalcin, and leptin. Men were followed for up to 7.4 years (average, 5.2 years). Poisson regression was used to investigate the relationship between serum adiponectin, other risk variables and the time-to-event hazard function of fracture. Median levels of serum adiponectin at baseline were 10.4 µg/mL (interquartile range, 7.7-14.3). During follow-up, 150 men sustained one or more fractures. The risk of fracture increased in parallel with increasing serum adiponectin (hazard ratio [HR]/SD, 1.46; 95% confidence interval [CI], 1.23-1.72) and persisted after multivariate-adjusted analysis (HR/SD, 1.30; 95% CI, 1.09-1.55). Serum adiponectin shows graded stepwise association with a significant excess risk of fracture in elderly men that was independent of several other risk factors for fracture. Its measurement holds promise as a risk factor for fracture in men.

  3. Globular adiponectin inhibits ethanol-induced apoptosis in HepG2 cells through heme oxygenase-1 induction.

    PubMed

    Nepal, Saroj; Kim, Mi Jin; Subedi, Amit; Lee, Eung-Seok; Yong, Chul Soon; Kim, Jung-Ae; Kang, WonKu; Kwak, Mi-Kyung; Arya, Dharamvir Singh; Park, Pil-Hoon

    2012-10-01

    Hepatocellular apoptosis is an essential pathological feature of alcoholic liver disease. Adiponectin, an adipokine predominantly secreted from adipose tissue, has been shown to play beneficial roles in alcoholic liver disease against various inflammatory and pro-apoptotic molecules. However, the effects of adiponectin on ethanol-induced apoptosis in liver cells are largely unknown. Herein, we investigated the role of globular adiponectin (gAcrp) in the prevention of ethanol-induced apoptosis and further tried to decipher the potential mechanisms involved. In the present study, we demonstrated that gAcrp significantly inhibits both ethanol-induced increase in Fas ligand expression and activation of caspase-3 in human hepatoma cell lines (HepG2 cells), suggesting that gAcrp plays a protective role against ethanol-induced apoptosis in liver cells. This protective effect of gAcrp was mediated through adiponectin receptor R1 (adipoR1). Further, globular adiponectin treatment caused induction of heme oxygenase-1 (HO-1) through, at least in part, nuclear factor (erythroid-derived 2)-like 2, (Nrf2) signaling. Treatment with SnPP, a pharmacological inhibitor of HO-1, and knockdown of HO-1 with small interfering RNA (siRNA) restored caspase-3 activity suppressed by gAcrp, indicating a critical role of HO-1 in mediating the protective role of gAcrp in ethanol-induced apoptosis in liver cells. In addition, carbon monoxide, a byproduct obtained from the catabolism of free heme was found to contribute to the anti-apoptotic effect of adiponectin. In conclusion, these data demonstrated that globular adiponectin prevents ethanol-induced apoptosis in HepG2 cells via HO-1 induction and revealed a novel biological response of globular adiponectin in the protection of liver injury from alcohol consumption.

  4. Effects of Rosuvastatin Alone or in Combination with Omega-3 Fatty Acid on Adiponectin Levels and Cardiometabolic Profile

    PubMed Central

    Al-Kuraishy, Hayder M.; Al-Gareeb, Ali I.

    2016-01-01

    Background: Adiponectin is an important adipocyte-related protein that has been postulated to participate in prevention of the development of metabolic syndrome. The relationship between adiponectin serum levels and risk of coronary artery disease (CAD) has been widely investigated and remains controversial. The aim of the present study was to evaluate the effects of rosuvastatin and/or omega-3 fatty acid on adiponectin serum levels in patients with insulin resistance (IR) and CAD. Patients and Methods: This study involved 87 patients with CADs and IR of different etiology, the patients were divided into three groups; 24 patients on treatment with rosuvastatin, 22 patients on treatment with omega-3 fatty acid, 23 patients on treatment with omega-3 fatty acid and rosuvastatin, 18 patients were not previously or currently treated with either rosuvastatin or omega-3 fatty acid, those regarded as control patients. Anthropometric measures, adiponectin serum levels, and other biochemical parameters were assessed in each treated group. Results: Rosuvastatin therapy leads to a significant elevation in adiponectin serum levels from 4.1 ± 0.99 ng/mL to 6.76 ± 1.03 ng/mL compared to control P < 0.01. Omega-3 fatty acid therapy leads to a significant elevation in adiponectin serum levels from 4.1 ± 0.99 ng/mL to 6.11 ± 1.29 ng/mL compared to control P < 0.01. Rosuvastatin plus omega-3 fatty acid therapy lead to a significant elevation in adiponectin serum levels from 4.1 ± 0.99 ng/mL to 7.99 ± 1.76 ng/mL compared to control P < 0.01. Conclusions: Rosuvastatin and/or omega-3 fatty acid lead to significant cardiometabolic protection through an increment in adiponectin serum levels. PMID:28104968

  5. B-type natriuretic peptide and adiponectin releases in rat model of myocardial damage induced by isoproterenol administration

    PubMed Central

    Hasić, Sabaheta; Hadžović-Džuvo, Almira; Jadrić, Radivoj; Kiseljaković, Emina

    2013-01-01

    B-type natriuretic peptide (BNP) and adiponectin play important role in the cardiovascular homeostasis regulation. We investigated BNP and adiponectin serum levels followed by isoproterenol (ISO) administration to rats and explored the relationship between them. Cardiac troponin I (cTnI) blood level was used as biochemical evidence of myocardial damage development. Adult male Wistar rats (average body weight 273.33±21.63 g) were distributed into groups: control group received saline (n=6) and ISO groups (n=12) treated with ISO (subcutaneous single dose 100 mg/kg of rat body weight). ISO group was divided into two groups according to the time of BNP, adiponectin and cTnI determination: ISO I (n=6; 2 hours after ISO administration); ISO II (n=6; 4 hours after ISO administration). Blood for determination of parameters was taken from rat abdominal aorta. BNP, adiponectin and cTnI were determined by ELISA method. Data were statistically analysed by using SPSS version13 computer program. P value less 0.05 was considered statistically significant. Blood BNP and adiponectin were lower at 2 hours after ISO administration in comparison with control group (p=0.004 for BNP and p=0.174 for adiponectin). Four hours after ISO administration, we have noted significant elevation of both parameters compared to ISO I group (p=0.004 for BNP;p=0.02 for adiponectin). Test of correlation have showed significant relation between their blood levels during experimental period (rho=0.577; p=0.01). BNP and adiponectin are not simple indicators of myocardial damage development. They have possible associated and additive effects in cardiovascular homeostasis regulation. PMID:24289757

  6. Inherent insulin sensitivity is a major determinant of multimeric adiponectin responsiveness to short-term weight loss in extreme obesity.

    PubMed

    Mai, Stefania; Walker, Gillian E; Brunani, Amelia; Guzzaloni, Gabriele; Grossi, Glenda; Oldani, Alberto; Aimaretti, Gianluca; Scacchi, Massimo; Marzullo, Paolo

    2014-07-24

    High molecular weight (HMW-A) adiponectin levels mirror alterations in glucose homeostasis better than medium (MMW-A) and low molecular weight (LMW-A) components. In 25 patients with wide-range extreme obesity (BMI 40-77 kg/m(2)), we aimed to explore if improvements of multimeric adiponectin following 4-wk weight loss reflect baseline OGTT-derived insulin sensitivity (ISIOGTT) and disposition index (DIOGTT). Compared to 40 lean controls, adiponectin oligomers were lower in extreme obesity (p < 0.001) and, within this group, HMW-A levels were higher in insulin-sensitive (p < 0.05) than -resistant patients. In obese patients, short-term weight loss did not change total adiponectin levels and insulin resistance, while the distribution pattern of adiponectin oligomers changed due to significant increment of HMW-A (p < 0.01) and reduction of MMW-A (p < 0.05). By multivariate analysis, final HMW-A levels were significantly related to baseline ISIOGTT and final body weight (adjusted R(2) = 0.41). Our data suggest that HMW adiponectin may reflect baseline insulin sensitivity appropriately in the context of extreme obesity. Especially, we documented that HMW-A is promptly responsive to short-term weight loss prior to changes in insulin resistance, by a magnitude that is proportioned to whole body insulin sensitivity. This may suggest an insulin sensitivity-dependent control operated by HMW-A on metabolic dynamics of patients with extreme obesity.

  7. Adiponectin enhances bone marrow mesenchymal stem cell resistance to flow shear stress through AMP-activated protein kinase signaling

    PubMed Central

    Zhao, Lin; Fan, Chongxi; Zhang, Yu; Yang, Yang; Wang, Dongjin; Deng, Chao; Hu, Wei; Ma, Zhiqiang; Jiang, Shuai; Di, Shouyi; Qin, Zhigang; Lv, Jianjun; Sun, Yang; Yi, Wei

    2016-01-01

    Adiponectin has been demonstrated to protect the cardiovascular system and bone marrow mesenchymal stem cells (BMSCs). However, it is unclear whether adiponectin can protect BMSCs against flow shear stress (FSS). In this study, our aim was to explore the effects of adiponectin on BMSCs and to explore the role of AMP-activated protein kinase (AMPK) signaling in this process. Shear stress significantly inhibits the survival and increases the apoptosis of BMSCs in an intensity-dependent manner. The expression levels of TGF-β, bFGF, VEGF, PDGF, and Bcl2 are simultaneously reduced, and the phosphorylation levels of AMPK and ACC, as well as the expression level of Bax, are increased. Supplementation with adiponectin promotes the survival of BMSCs; reverses the changes in the expression levels of TGF-β, bFGF, VEGF, PDGF, Bcl2, and Bax; and further amplifies the phosphorylation of AMPK and ACC. Furthermore, the protective effects of adiponectin can be partially neutralized by AMPK siRNA. In summary, we have demonstrated for the first time that adiponectin can effectively protect BMSCs from FSS and that this effect depends, at least in part, on the activation of AMPK signaling. PMID:27418435

  8. Effects of L-thyroxine therapy on circulating leptin and adiponectin levels in subclinical hypothyroidism: a prospective study.

    PubMed

    Yildiz, Bulent Okan; Aksoy, Duygu Yazgan; Harmanci, Ayla; Unluturk, Ugur; Cinar, Nese; Isildak, Mehlika; Usman, Aydan; Bayraktar, Miyase

    2013-05-01

    Subclinical hypothyroidism (SCH) is defined by increased thyrotropin (TSH) and normal free thyroxine (fT4) levels. Controversial data are available regarding the effects of SCH on adipose tissue. Adiponectin and leptin are two major adipokines secreted from adipose tissue. We aimed to determine the levels of adiponectin and leptin in women with SCH and potential effects of L-thyroxine therapy on those levels. Forty three women with SCH and 53 age- and BMI-matched healthy euthyroid control women were included. Adiponectin and leptin levels, total cholesterol (TC), triglycerides (TG), HDL-, and LDL cholesterol, fat mass (FM) and fat-free mass (FFM) were determined in all participants. Patients received L-thyroxine treatment for 6 months after which all measurements were repeated. Patients with SCH and controls had similar baseline values for adiponectin, leptin, lipids, FM and FFM. All patients reached euthyroid status after 6 months of replacement therapy. Treatment resulted in an increase in adiponectin (p <0.01) and a decrease in leptin levels (p <0.05). Lipid levels, FM and FFM did not show a significant change. Achievement of euthyroid status by replacement therapy increases adiponectin and decreases leptin levels in women with SCH in this prospective study independent of a change in body fat mass.

  9. Low plasma adiponectin level, white blood cell count and Helicobacter pylori titre independently predict abnormal pancreatic beta-cell function.

    PubMed

    So, Wing-Yee; Tong, Peter C; Ko, Gary T; Ma, Ronald C; Ozaki, Risa; Kong, Alice P; Yang, Xilin; Ho, Chung-Shun; Lam, Christopher C; Chan, Juliana C

    2009-11-01

    Adiponectin is an adipocytokine with insulin sensitizing effect while chronic inflammation damages pancreatic beta-cells leading to reduced insulin response. We aimed to prove the hypothesis that adiponectin levels and inflammatory markers (white blood cell counts [WCC], Helicobacter pylori [HP] titers, high sensitivity C-reactive protein [hs-CRP]) may interact to affect risk of diabetes. We studied 288 Chinese men (age-median: 41.0 years, IQR: 35.3-46.0 years) being recruited from the community in Hong Kong. The mean adiponectin level was 5.39+/-2.81 microg/ml and 40.9% (n=107) had low adiponectin level (<4 microg/ml). On multiple regression analysis, adiponectin was negatively associated with diabetes, HOMA insulin resistance top quartile, plasma glucose (PG) and 2h insulin; and positively associated with HOMA insulin sensitivity index. WCC was independently associated with PG and 15' insulin, and negatively associated with HOMA insulin sensitivity top quartile. HP titre was associated with 30' PG level and diabetes. hs-CRP did not enter the multivariable model. In conclusion, adiponectin, WCC and HP titer are independent predictors for hyperglycemia and reduced insulin sensitivity in Chinese men. These findings may explain the high risk for diabetes in Chinese population despite their relatively low adiposity.

  10. Obesity indices and metabolic markers are related to hs-CRP and adiponectin levels in overweight and obese females.

    PubMed

    Sanip, Zulkefli; Ariffin, Farah Diana; Al-Tahami, Belqes Abdullah Mohammed; Sulaiman, Wan Azman Wan; Rasool, Aida Hanum Ghulam

    2013-01-01

    Obese subjects had increased serum high sensitivity C-reactive protein (hs-CRP), decreased adiponectin levels, and impaired microvascular endothelial function compared to lean subjects. We investigated the relationships of serum hs-CRP, adiponectin and microvascular endothelial function with obesity indices and metabolic markers in overweight and obese female subjects. Anthropometric profile, body fat composition, biochemical analysis, serum hs-CRP and adiponectin levels, and microvascular endothelial function were measured in 91 female subjects. Microvascular endothelial function was determined using laser Doppler fluximetry and the process of iontophoresis. Mean age and body mass index (BMI) of subjects were 34.88 (7.87) years and 32.93 (4.82) kg/m(2). hs-CRP levels were positively correlated with weight, BMI, waist circumference, hip circumference, body fat and visceral fat. Adiponectin levels were positively correlated with insulin sensitivity index (HOMA-%S), and inversely correlated with waist hip ratio, triglyceride, fasting insulin and insulin resistance index (HOMA-IR). No relationship was seen between microvascular endothelial function and obesity indices, and metabolic markers. In overweight and obese female subjects, hs-CRP levels were correlated with obesity indices while adiponectin levels were inversely correlated with obesity indices and metabolic markers. No significant relationship was seen between microvascular endothelial function with obesity indices and metabolic markers including hs-CRP and adiponectin in female overweight and obese subjects.

  11. Association of adiponectin and leptin with relative telomere length in seven independent cohorts including 11,448 participants.

    PubMed

    Broer, Linda; Raschenberger, Julia; Deelen, Joris; Mangino, Massimo; Codd, Veryan; Pietiläinen, Kirsi H; Albrecht, Eva; Amin, Najaf; Beekman, Marian; de Craen, Anton J M; Gieger, Christian; Haun, Margot; Henneman, Peter; Herder, Christian; Hovatta, Iiris; Laser, Annika; Kedenko, Lyudmyla; Koenig, Wolfgang; Kollerits, Barbara; Moilanen, Eeva; Oostra, Ben A; Paulweber, Bernhard; Quaye, Lydia; Rissanen, Aila; Roden, Michael; Surakka, Ida; Valdes, Ana M; Vuolteenaho, Katriina; Thorand, Barbara; van Dijk, Ko Willems; Kaprio, Jaakko; Spector, Tim D; Slagboom, P Eline; Samani, Nilesh J; Kronenberg, Florian; van Duijn, Cornelia M; Ladwig, Karl-Heinz

    2014-09-01

    Oxidative stress and inflammation are major contributors to accelerated age-related relative telomere length (RTL) shortening. Both conditions are strongly linked to leptin and adiponectin, the most prominent adipocyte-derived protein hormones. As high leptin levels and low levels of adiponectin have been implicated in inflammation, one expects adiponectin to be positively associated with RTL while leptin should be negatively associated. Within the ENGAGE consortium, we investigated the association of RTL with adiponectin and leptin in seven independent cohorts with a total of 11,448 participants. We performed partial correlation analysis on Z-transformed RTL and LN-transformed leptin/adiponectin, adjusting for age and sex. In extended models we adjusted for body mass index (BMI) and C-reactive protein (CRP). Adiponectin showed a borderline significant association with RTL. This appeared to be determined by a single study and when the outlier study was removed, this association disappeared. The association between RTL and leptin was highly significant (r = -0.05; p = 1.81 × 10(-7)). Additional adjustment for BMI or CRP did not change the results. Sex-stratified analysis revealed no difference between men and women. Our study suggests that high leptin levels are associated with short RTL.

  12. C-reactive protein inhibits high-molecular-weight adiponectin expression in 3T3-L1 adipocytes via PI3K/Akt pathway.

    PubMed

    Liu, Yuanxin; Liu, Cuiping; Jiang, Chao; Wang, Su; Yang, Qichao; Jiang, Dan; Yuan, Guoyue

    2016-03-25

    Adiponectin, an adipose-specific protein hormone, is secreted from white adipose tissue and involved in glucose and lipid metabolism. It is assembled into low-molecular-weight trimer (LMW), middle-molecular-weight hexameric (MMW) and high-molecular-weight (HMW), among which HMW exhibits higher activity. In this study, we proved that C-reactive protein (CRP), an inflammatory marker, inhibited adiponectin expression, especially HMW in time-and dose-dependent manners. Furthermore, CRP decreased the HMW/total adiponectin ration and reduced adiponectin assembly by increasing ERp44, and decreasing Ero1-α and DsbA-L. CRP activated pAkt, the downstream of PI3K. Inhibition of PI3K or pAkt abolished the effect of CRP. Our study suggested that CRP decreased adiponectin expression and multimerization, while CRP-induced decline in adiponectin might be mediated through the PI3K/Akt pathway.

  13. Normal total and high molecular weight adiponectin levels in adults with cystic fibrosis.

    PubMed

    Ziai, S; Elisha, B; Hammana, I; Tardif, A; Berthiaume, Y; Coderre, L; Rabasa-Lhoret, R

    2011-12-01

    Cystic fibrosis related diabetes (CFRD) is an important complication of CF that increases mortality. Adiponectin, an adipokine secreted from adipose tissue, plays an important role in fatty acid and glucose metabolism. Lower total adiponectin (TA) levels have been linked to the risk of developing type 2 diabetes. However, studies show that the high molecular weight isoform (HMW), thought to be more active than TA, might be a better indicator of insulin sensitivity. Our aim was to determine the association between HMW and insulin sensitivity in CF subjects and determine if other factors might modulate its levels. Thirteen control subjects and 47 CF adults (16 with normal glucose tolerance, 16 prediabetic and 15 with CFRD) underwent an oral glucose tolerance test. Blood samples were taken at time 0, 30, 60, 90 and 120 min. Body mass index, fibrinogen, glucose and insulin, TA and HMW were measured in every subject. Regression analysis was used to determine the association between TA, HMW and glucose (fasting glucose, 2h glucose and glucose AUC) as well as insulin (fasting insulin, insulin AUC, and Stumvoll insulin sensitivity index) parameters. TA and HMW levels were similar between CF patients and controls and were not associated to insulin sensitivity. TA was negatively associated to insulin AUC (p=0.0108) and 2h glucose (p=0.0116) in controls while these relationships were either weakly negative (p=0.0208) or weakly positive (p=0.0105) in CF patients. Also, HMW was negatively associated to insulin (p=0.00301) and glucose AUC (p=0.0546) in controls whereas these associations were positive in CF patients (p=0.0388, p=0.0232 respectively). In conclusion, our exploratory study on HMW adiponectin demonstrated similar levels of TA and HMW between CF patients and controls and different relationships between forms of adiponectin to glucose metabolism and insulin in CF.

  14. Effects of soy protein and isoflavones on insulin resistance and adiponectin in male monkeys.

    PubMed

    Wagner, Janice D; Zhang, Li; Shadoan, Melanie K; Kavanagh, Kylie; Chen, Haiying; Tresnasari, Kristianti; Kaplan, Jay R; Adams, Michael R

    2008-07-01

    Isoflavones may influence insulin action by means of their well-known receptor-mediated estrogenic activity. However, isoflavones also bind to peroxisome proliferator-activated receptors (PPARs) that are strongly associated with insulin action. Soy protein with its isoflavones has previously been shown to improve glycemic control in diabetic postmenopausal women and to improve insulin sensitivity in ovariectomized monkeys. The purpose of the current report was to extend our studies of dietary soy protein to male monkeys and determine effects of the soy isoflavones on insulin resistance. Two studies are reported here. Study one involved 91 male monkeys consuming 3 diets differing only by the source of protein (casein-lactalbumin, soy protein with a low isoflavone concentration, or soy protein with a high isoflavone concentration). Intravenous glucose tolerance tests were done, and plasma adiponectin and lipoprotein concentrations were determined after 25 months of study. Samples of visceral fat were obtained at 31 months for assessment of adiponectin and PPARgamma expression. The second study involved 8 monkeys in a Latin-square design that compared the effects of diets with casein/lactalbumin, soy protein with a high isoflavone concentration, or soy protein that was alcohol-washed to deplete the isoflavones. After 8 weeks of treatment, insulin sensitivity and plasma lipoproteins were assessed. At 10 weeks, a biopsy of the skeletal muscle was performed for determination of insulin receptor, PPARalpha, and PPARgamma content. The major findings were that consumption of isoflavone-containing soy protein dose-dependently increased insulin responses to the glucose challenge and decreased plasma adiponectin, whereas isoflavone-depleted soy protein decreased body weight and had no effect on plasma adiponectin concentrations. Muscle PPARalpha and gamma expression was also increased with the isoflavone-depleted soy relative to either casein or soy protein containing the

  15. Adiponectin in eutrophic and obese children as a biomarker to predict metabolic syndrome and each of its components

    PubMed Central

    2013-01-01

    Background Obesity is associated with the rise of noncommunicable diseases worldwide. The pathophysiology behind this disease involves the increase of adipose tissue, being inversely related to adiponectin, but directly related to insulin resistance and metabolic syndrome (MetS). Therefore, this study aimed to determine the relationship between adiponectin levels with each component of MetS in eutrophic and obese Mexican children. Methods A cross sectional study was conducted in 190 school-age children classified as obese and 196 classified as eutrophic. Adiponectin, glucose, insulin, high density lipoprotein cholesterol (HDL-C) and triglycerides were determined from a fasting blood sample. Height, weight, waist circumference, systolic and diastolic blood pressures (BP) were measured; MetS was evaluated with the IDF definition. The study groups were divided according to tertiles of adiponectin, using the higher concentration as a reference. Linear regression analysis was used to assess the association between adiponectin and components of the MetS. Finally, stepwise forward multiple logistic regression analysis controlling for age, gender, basal HOMA-IR values and BMI was performed to determine the odds ratio of developing MetS according to adiponectin tertiles. Results Anthropometric and metabolic measurements were statistically different between eutrophic and obese children with and without MetS (P <0.001). The prevalence of MetS in obese populations was 13%. Adiponectin concentrations were 15.5 ± 6.1, 12.0 ± 4.8, 12.4 ± 4.9 and 9.4 ± 2.8 μg/mL for eutrophic and obese subjects, obese without MetS, and obese with MetS, respectively (P <0.001). Obese children with low values of adiponectin exhibited a higher frequency of MetS components: abdominal obesity, 49%; high systolic BP, 3%; high diastolic BP, 2%; impaired fasting glucose, 17%; hypertriglyceridemia, 31%; and low HDL-C values, 42%. Adjusted odds ratio of presenting MetS according to

  16. Gender differences in the association of visceral and subcutaneous adiposity with adiponectin in African Americans: the Jackson Heart Study

    PubMed Central

    2013-01-01

    Background Adiponectin, paradoxically reduced in obesity and with lower levels in African Americans (AA), modulates several cardiometabolic risk factors. Because abdominal visceral adipose tissue (VAT), known to be reduced in AA, and subcutaneous adipose tissue (SAT) compartments may confer differential metabolic risk profiles, we investigated the associations of VAT and SAT with serum adiponectin, separately by gender, with the hypothesis that VAT is more strongly inversely associated with adiponectin than SAT. Methods Participants from the Jackson Heart Study, an ongoing cohort of AA (n = 2,799; 64% women; mean age, 55 ± 11 years) underwent computer tomography assessment of SAT and VAT volumes, and had stored serum specimens analyzed for adiponectin levels. These levels were examined by gender in relation to increments of VAT and SAT. Results Compared to women, men had significantly lower mean levels of adiponectin (3.9 ± 3.0 μg/mL vs. 6.0 ± 4.4 μg/mL; p < 0.01) and mean volume of SAT (1,721 ± 803 cm3 vs. 2,668 ± 968 cm3; p < 0.01) but significantly higher mean volume of VAT (884 ± 416 cm3 vs. 801 ± 363 cm3; p < 0.01). Among women, a one standard deviation increment in VAT was inversely associated with adiponectin (β = − 0.13; p < 0.0001) after controlling for age, systolic blood pressure, fasting plasma glucose, high-density lipoprotein cholesterol, triglycerides, education, pack-years of smoking and daily intake of alcohol. The statistically significant inverse association of VAT and adiponectin persisted after additionally adjusting for SAT, body mass index (BMI) and waist circumference (WC), suggesting that VAT provides significant information above and beyond BMI and WC. Among men, after the same multivariable adjustment, there was a direct association of SAT and adiponectin (β = 0.18; p = 0.002) that persisted when controlling for BMI and WC, supporting a beneficial effect of

  17. Feeding a Modified Fish Diet to Bottlenose Dolphins Leads to an Increase in Serum Adiponectin and Sphingolipids

    PubMed Central

    Sobolesky, Philip M.; Harrell, Tyler S.; Parry, Celeste; Venn-Watson, Stephanie; Janech, Michael G.

    2016-01-01

    Feeding a modified fish diet has been suggested to improve insulin sensitivity in bottlenose dolphins; however, insulin sensitivity was not directly measured. Since demonstrating an improvement in insulin sensitivity is technically difficult in dolphins, we postulated that directional changes in the hormone axis: fibroblast growth factor 21 (FGF21)/Adiponectin/Ceramide (Cer), could provide further support to this hypothesis. We measured 2-h post-prandial serum FGF21, total adiponectin, percent unmodified adiponectin, ceramide, and sphingosine levels from dolphins fed a diet rich in heptadecanoic acid (C17:0) over 24 weeks. Serum FGF21 was quantified by ELISA with an observed range of 129–1599 pg/ml, but did not significantly change over the 24-week study period. Total adiponectin levels (mean ± SD) significantly increased from 776 ± 400 pmol/ml at week 0 to 1196 ± 467 pmol/ml at week 24. The percent unmodified adiponectin levels (mean ± SD) decreased from 23.8 ± 6.0% at week 0 to 15.2 ± 5.2% at week 24. Interestingly, although FGF21 levels did not change, there was a good correlation between FGF21 and total adiponectin (ρ = 0.788, P < 0.001). We quantified the abundances of serum ceramides and sphingosines (SPH) because adiponectin has a defined role in sphingolipid metabolism through adiponectin receptor-mediated activation of ceramidases. The most abundant ceramide in dolphin sera was Cer 24:1 comprising 49% of the ceramides measured. Significant reductions were observed in the unsaturated Cer 18:1, Cer 20:1, and Cer 24:1, whereas significant increases were observed in saturated Cer 22:0, Cer 24:0, and Cer 26:0. However, total serum ceramides did not change. Significant elevations were detected for total sphingosine, dihydrosphingosine, sphingosine-1-phosphate, and dihydrosphingosine-1-phosphate. Proteomic analysis of the serum proteins revealed few changes in serum proteins over the study period. In conclusion

  18. Ratiometric Measurements of Adiponectin by Mass Spectrometry in Bottlenose Dolphins (Tursiops truncatus) with Iron Overload Reveal an Association with Insulin Resistance and Glucagon

    PubMed Central

    Neely, Benjamin A.; Carlin, Kevin P.; Arthur, John M.; McFee, Wayne E.; Janech, Michael G.

    2013-01-01

    High molecular weight (HMW) adiponectin levels are reduced in humans with type 2 diabetes and insulin resistance. Similar to humans with insulin resistance, managed bottlenose dolphins (Tursiops truncatus) diagnosed with hemochromatosis (iron overload) have higher levels of 2 h post-prandial plasma insulin than healthy controls. A parallel reaction monitoring assay for dolphin serum adiponectin was developed based on tryptic peptides identified by mass spectrometry. Using identified post-translational modifications, a differential measurement was constructed. Total and unmodified adiponectin levels were measured in sera from dolphins with (n = 4) and without (n = 5) iron overload. This measurement yielded total adiponectin levels as well as site specific percent unmodified adiponectin that may inversely correlate with HMW adiponectin. Differences in insulin levels between iron overload cases and controls were observed 2 h post-prandial, but not during the fasting state. Thus, post-prandial as well as fasting serum adiponectin levels were measured to determine whether adiponectin and insulin would follow similar patterns. There was no difference in total adiponectin or percent unmodified adiponectin from case or control fasting animals. There was no difference in post-prandial total adiponectin levels between case and control dolphins (mean ± SD) at 763 ± 298 and 727 ± 291 pmol/ml, respectively (p = 0.91); however, percent unmodified adiponectin was significantly higher in post-prandial cases compared to controls (30.0 ± 6.3 versus 17.0 ± 6.6%, respectively; p = 0.016). Interestingly, both total and percent unmodified adiponectin were correlated with glucagon levels in controls (r = 0.999, p  < 0.001), but not in cases, which is possibly a reflection of insulin resistance. Although total adiponectin levels were not significantly different, the elevated percent unmodified adiponectin follows a trend similar to

  19. Cardioprotective effect of intermittent fasting is associated with an elevation of adiponectin levels in rats.

    PubMed

    Wan, Ruiqian; Ahmet, Ismayil; Brown, Martin; Cheng, Aiwu; Kamimura, Naomi; Talan, Mark; Mattson, Mark P

    2010-05-01

    It has been reported that dietary energy restriction, including intermittent fasting (IF), can protect heart and brain cells against injury and improve functional outcome in animal models of myocardial infarction (MI) and stroke. Here we report that IF improves glycemic control and protects the myocardium against ischemia-induced cell damage and inflammation in rats. Echocardiographic analysis of heart structural and functional variables revealed that IF attenuates the growth-related increase in posterior ventricular wall thickness, end systolic and diastolic volumes, and reduces the ejection fraction. The size of the ischemic infarct 24 h following permanent ligation of a coronary artery was significantly smaller, and markers of inflammation (infiltration of leukocytes in the area at risk and plasma IL-6 levels) were less, in IF rats compared to rats on the control diet. IF resulted in increased levels of circulating adiponectin prior to and after MI. Because recent studies have shown that adiponectin can protect the heart against ischemic injury, our findings suggest a potential role for adiponectin as a mediator of the cardioprotective effect of IF.

  20. Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin.

    PubMed

    Yau, Suk Yu; Li, Ang; Hoo, Ruby L C; Ching, Yick Pang; Christie, Brian R; Lee, Tatia M C; Xu, Aimin; So, Kwok-Fai

    2014-11-04

    Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood-brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression.

  1. Activation of autophagy by globular adiponectin is required for muscle differentiation.

    PubMed

    Gamberi, Tania; Modesti, Alessandra; Magherini, Francesca; D'Souza, Donna M; Hawke, Thomas; Fiaschi, Tania

    2016-04-01

    Regulated autophagy is a critical component for a healthy skeletal muscle mass, such that dysregulation of the autophagic processes correlates with severe myopathies. Thus, defining the biological molecules involved in the autophagic processes within skeletal muscle is of great importance. Here we demonstrate that globular adiponectin (gAd) activates autophagy in skeletal muscle myoblasts via an AMPK-dependent mechanism. Activation of autophagy through gAd promotes myoblast survival and apoptosis inhibition during serum starvation and the gAd-activated autophagy orchestrates the myogenic properties of the hormone. Consistent with this conclusion, inhibition of gAd-activated autophagy by both a pharmacological (chloroquine) or siRNA approach greatly inhibited muscle differentiation, as demonstrated by reductions in myosin heavy chain expression and myotube formation. Further support for the role of adiponectin in autophagy comes from the skeletal muscles of adiponectin KO mice which display decreased LC3 II expression and a myopathic phenotype (heterogeneous fiber sizes, numerous central nuclei). Overall, these findings demonstrate that gAd activates autophagy in myoblasts and that gAd-activated autophagy drives the myogenic properties of this hormone.

  2. Ghrelin, leptin, adiponectin, and resistin levels in sleep apnea syndrome: Role of obesity

    PubMed Central

    Ursavas, Ahmet; Ilcol, Yesim Ozarda; Nalci, Nazan; Karadag, Mehmet; Ege, Ercument

    2010-01-01

    AIM: The aim of this study was to investigate the relationship among plasma leptin, ghrelin, adiponectin, resistin levels, and obstructive sleep apnea syndrome (OSAS). METHODS: Fifty-five consecutive newly diagnosed OSAS patients and 15 age-matched nonapneic controls were enrolled in this study. After sleep study between 8:00 AM and 9:00 AM on the morning, venous blood was obtained in the fasting state to measure ghrelin and adipokines. RESULTS: Serum ghrelin levels of OSAS group were significantly (P < 0.05) higher than those of the control group. No significant difference was noted in the levels of leptin, adiponectin, and resistin in OSAS group when compared to controls. There was a significant positive correlation between ghrelin and apnea–hypopnea index (AHI) (r = 0.237, P < 0.05) or the Epworth sleepiness scale (ESS) (r = 0.28, P < 0.05). There was also a significant positive correlation between leptin and body mass index (r = 0.592, P < 0.0001). No significant correlation was observed between leptin, adiponectin, resistin, and any polysomnographic parameters. CONCLUSION: Our findings demonstrated that serum ghrelin levels were higher in OSAS patients than those of control group and correlated with AHI and ESS. Further studies are needed to clarify the complex relation among OSAS, obesity, adipokines, and ghrelin. PMID:20835311

  3. Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin

    PubMed Central

    Yau, Suk Yu; Li, Ang; Hoo, Ruby L. C.; Ching, Yick Pang; Christie, Brian R.; Lee, Tatia M. C.; Xu, Aimin; So, Kwok-Fai

    2014-01-01

    Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood–brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression. PMID:25331877

  4. Plasma insulin, leptin, adiponectin, resistin, ghrelin, and melatonin in nonalcoholic steatohepatitis patients treated with melatonin.

    PubMed

    Gonciarz, Maciej; Bielański, Wladyslaw; Partyka, Robert; Brzozowski, Tomasz; Konturek, Piotr C; Eszyk, Jerzy; Celiński, Krzysztof; Reiter, Russel J; Konturek, Stanislaw J

    2013-03-01

    Insulin resistance, oxidative stress, and an abnormal production of adipokines and cytokines are implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH). Recently, we reported a significant improvement in plasma liver enzymes among patients with NASH treated with melatonin. In this study, we investigated the effect of melatonin, administered at a dose of 10 mg/day for 28 days to 16 patients with histologically proven NASH on insulin resistance (HOMA-IR), on the plasma levels of adiponectin, leptin, ghrelin, and resistin. Additionally, plasma levels of aminotransferases and gamma glutamyltranspeptidase as well as plasma concentrations of melatonin were evaluated. Median baseline values of HOMA-IR, leptin (ng/mL), and resistin (pg/mL) in patients with NASH were significantly higher in comparison with controls: 4.90 versus 1.60, 10.70 versus 4.30, and 152 versus 91, respectively. Median adiponectin level (μg/mL) was decreased in patients compared to controls: 6.40 versus 16.25; no significant difference in ghrelin levels between patients and controls was found. After melatonin treatment, the median value of HOMA-IR was significantly reduced by 60% as compared to baseline values, whereas adiponectin, leptin, and ghrelin plasma levels rose significantly by 119%, 33%, and 20%, respectively; the difference between pre-/posttreatment in plasma resistin levels was not significant. These findings make melatonin a suitable candidate for testing in patients with NASH in the large controlled clinical trials.

  5. Ethnicity Modifies the Relationships of Insulin Resistance, Inflammation, and Adiponectin With Obesity in a Multiethnic Asian Population

    PubMed Central

    Khoo, Chin Meng; Sairazi, Sarina; Taslim, Siska; Gardner, Daphne; Wu, Yi; Lee, Jeannette; van Dam, Rob M.; Shyong Tai, E.

    2011-01-01

    OBJECTIVE The development of obesity-related metabolic disorders varies with ethnicity. We examined whether ethnicity modifies the relationship between BMI and three metabolic pathways (insulin resistance, inflammation, and adiponectin) that are involved in the pathogenesis of diabetes and cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS We analyzed data from 4,804 Chinese, Malay, and Asian-Indian residents of Singapore with complete data on insulin resistance (IR), C-reactive protein (CRP), and total adiponectin levels. Linear regression models with an interaction term ethnicity*BMI were used to evaluate whether ethnicity modifies the association between BMI and IR, CRP, and adiponectin. RESULTS In both uni- and multivariate analyses, BMI was directly associated with IR and CRP and inversely with adiponectin across all ethnic groups. When compared with Chinese and Malays, Asian-Indians had higher IR and CRP and lower adiponectin levels. The associations between BMI and its metabolic pathways were significantly stronger in Chinese than in other ethnic groups. The increase in IR and CRP and the decrease in adiponectin for each unit increase in BMI were greater in Chinese than in other ethnic groups. The findings were similar when waist circumference was used in the analyses instead of BMI. CONCLUSIONS The impact of BMI on IR, CRP, and adiponectin appears greater in Chinese as compared with other major Asian ethnic groups. This may partly explain the rapid increase in the prevalence of diabetes and CVD in Chinese populations and highlights the importance of weight management in Asian ethnic groups despite the apparently low levels of obesity. PMID:21464462

  6. Visceral Fat Area and Serum Adiponectin Level Predict the Development of Metabolic Syndrome in a Community-Based Asymptomatic Population

    PubMed Central

    Cho, Jae-Young; Lee, Seung Hun; Park, Jae Hyoung; Hong, Soon Jun; Yu, Cheol Woong; Lim, Do-Sun

    2017-01-01

    Background Although it has been demonstrated that visceral adipose tissue content and serum levels of adiponectin are associated with metabolic syndrome, their predictive potential for the development of metabolic syndrome remains to be elucidated. Methods We studied 1,130 participants of the Seoul Metabolic Syndrome cohort. A total of 337 subjects without metabolic syndrome underwent the follow-up evaluation and finally analyzed. Visceral fat area (VFA) was measured using dual bioelectrical impedance analysis. We compared the 1-year incidence rate of metabolic syndrome among four different groups: Group 1 (high adiponectin level and low VFA), Group 2 (low adiponectin level and low VFA), Group 3 (high adiponectin level and high VFA) and Group 4 (low adiponectin level and high VFA). Results Median follow-up duration was 17 months. Cut-off points of adiponectin level and VFA for metabolic syndrome were 7.34 ng/ml and 84 cm2 for men, and 12.55 and 58 cm2 ng/ml for women, respectively. The incidence of metabolic syndrome was the highest in Group 4 (Group 1; 16.47%, Group 2; 22.08%, Group 3; 25%, and Group 4; 46.15%, p<0.001). Adjusted logistic regression analyses for metabolic syndrome prediction demonstrated that Group 4 exhibited the highest odds ratio compared with Group 1 (4.918 [2.05–11.795]), which was predominantly affected by waist circumference and serum triglyceride levels. Notably, triglyceride/high-density lipoprotein cholesterol (TG/HDL) ratio was significantly higher in Group 4 (p = 0.017). Conclusion Incidence rate of metabolic syndrome was the highest in subjects with low serum adiponectin levels and high visceral fat area. Higher TG/HDL ratio in these subjects suggested insulin resistance may contribute to the development of metabolic syndrome. PMID:28046037

  7. Chronic effects of centrally administered adiponectin on appetite, metabolism and blood pressure regulation in normotensive and hypertensive rats.

    PubMed

    Bassi, Mirian; do Carmo, Jussara M; Hall, John E; da Silva, Alexandre A

    2012-09-01

    Acute studies suggest that adiponectin may reduce sympathetic activity and blood pressure (BP) via actions on the central nervous system (CNS). However, the chronic effects of adiponectin on energy expenditure and cardiovascular function are still poorly understood. We tested if chronic intracerebroventricular (ICV) infusion of adiponectin (1 or 7μg/day) in Sprague-Dawley rats fed a high fat diet (HFD) for 8 weeks and at the high dose (7μg/day) in spontaneously hypertensive rats (SHRs), a hypertensive model associated with sympathetic overactivity, evoked chronic reductions in BP and heart rate (HR). We also determined if chronic ICV adiponectin infusion alters appetite, whole body oxygen consumption (VO(2)), and insulin and leptin levels. Neither dose of adiponectin infused for 7 days significantly altered BP or HR in the HFD group (115±2 to 112±2mmHg and 384±6 to 379±6bpm at 1μg/day; 109±3 to 111±3mmHg and 366±5 and 367±5bpm at 7μg/day). The higher dose slightly reduced food intake (14±1 to 11±1g/day), whereas VO(2), insulin and leptin levels were not affected by the treatment. In SHRs, ICV adiponectin infusion reduced appetite (22±2 to 12±2g/day) and insulin levels (∼55%), but did not alter BP (162±4 to 164±3mmHg) or HR (312±5 to 322±8bpm). These results suggest that adiponectin, acting via its direct actions on the CNS, has a small effect to reduce appetite and insulin levels, but it has no long-term action to reduce BP or HR, or to alter whole body metabolic rate.

  8. CHRONIC EFFECTS OF CENTRALLY ADMINISTERED ADIPONECTIN ON APPETITE, METABOLISM AND BLOOD PRESSURE REGULATION IN NORMOTENSIVE AND HYPERTENSIVE RATS

    PubMed Central

    Bassi, Mirian; do Carmo, Jussara M.; Hall, John E.; da Silva, Alexandre A.

    2012-01-01

    Acute studies suggest that adiponectin may reduce sympathetic activity and blood pressure (BP) via actions on the central nervous system (CNS). However, the chronic effects of adiponectin on energy expenditure and cardiovascular function are still poorly understood. We tested if chronic intracerebroventricular (ICV) infusion of adiponectin (1 or 7 µg/day) in Sprague-Dawley rats fed a high fat diet (HFD) for 8 weeks and at the high dose (7 µg/day) in spontaneously hypertensive rats (SHR), a hypertensive model associated with sympathetic overactivity, evoked chronic reductions in BP and heart rate (HR). We also determined if chronic ICV adiponectin infusion alters appetite, whole body oxygen consumption (VO2), and insulin and leptin levels. Neither dose of adiponectin infused for 7 days significantly altered BP or HR in the HFD group (115±2 to 112±2 mmHg and 384±6 to 379±6 bpm at 1 µg/day; 109±3 to 111±3 mmHg and 366±5 and 367±5 bpm at 7µg/day). The higher dose slightly reduced food intake (14±1 to 11±1 g/day), whereas VO2, insulin and leptin levels were not affected by the treatment. In SHRs, ICV adiponectin infusion reduced appetite (22±2 to 12±2 g/day) and insulin levels (~55%), but did not alter BP (162±4 to 164±3 mmHg) or HR (312±5 to 322±8 bpm). These results suggest that adiponectin, acting via its direct actions on the CNS, has a small effect to reduce appetite and insulin levels, but it has no long-term action to reduce BP or HR, or to alter whole body metabolic rate. PMID:22749987

  9. Adiponectin and AMP kinase activator stimulate proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells

    PubMed Central

    Kanazawa, Ippei; Yamaguchi, Toru; Yano, Shozo; Yamauchi, Mika; Yamamoto, Masahiro; Sugimoto, Toshitsugu

    2007-01-01

    Background Adiponectin is a key mediator of the metabolic syndrome that is caused by visceral fat accumulation. Adiponectin and its receptors are known to be expressed in osteoblasts, but their actions with regard to bone metabolism are still unclear. In this study, we investigated the effects of adiponectin on the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells. Results Adiponectin receptor type 1 (AdipoR1) mRNA was detected in the cells by RT-PCR. The adenosine monophosphate-activated protein kinase (AMP kinase) was phosphorylated by both adiponectin and a pharmacological AMP kinase activator, 5-amino-imidazole-4-carboxamide-riboside (AICAR), in the cells. AdipoR1 small interfering RNA (siRNA) transfection potently knocked down the receptor mRNA, and the effect of this knockdown persisted for as long as 10 days after the transfection. The transfected cells showed decreased expressions of type I collagen and osteocalcin mRNA, as determined by real-time PCR, and reduced ALP activity and mineralization, as determined by von Kossa and Alizarin red stainings. In contrast, AMP kinase activation by AICAR (0.01–0.5 mM) in wild-type MC3T3-E1 cells augmented their proliferation, differentiation, and mineralization. BrdU assay showed that the addition of adiponectin (0.01–1.0 μg/ml) also promoted their proliferation. Osterix, but not Runx-2, appeared to be involved in these processes because AdipoR1 siRNA transfection and AICAR treatments suppressed and enhanced osterix mRNA expression, respectively. Conclusion Taken together, this study suggests that adiponectin stimulates the proliferation, differentiation, and mineralization of osteoblasts via the AdipoR1 and AMP kinase signaling pathways in autocrine and/or paracrine fashions. PMID:18047638

  10. Chlorogenic Acid Improves Late Diabetes through Adiponectin Receptor Signaling Pathways in db/db Mice

    PubMed Central

    Jin, Shasha; Chang, Cuiqing; Zhang, Lantao; Liu, Yang; Huang, Xianren; Chen, Zhimin

    2015-01-01

    The aim of this study was to examine the effects of chlorogenic acid (CGA) on glucose and lipid metabolism in late diabetic db/db mice, as well as on adiponectin receptors and their signaling molecules, to provide evidence for CGA in the prevention of type 2 diabetes. We randomly divided 16 female db/db mice into db/db-CGA and db/db-control (CON) groups equally; db/m mice were used as control mice. The mice in both the db/db-CGA and db/m-CGA groups were administered 80 mg/kg/d CGA by lavage for 12 weeks, whereas the mice in both CON groups were given equal volumes of phosphate-buffered saline (PBS) by lavage. At the end of the intervention, we assessed body fat and the parameters of glucose and lipid metabolism in the plasma, liver and skeletal muscle tissues as well as the levels of aldose reductase (AR) and transforming growth factor-β1 (TGF-β1) in the kidneys and measured adiponectin receptors and the protein expression of their signaling molecules in liver and muscle tissues. After 12 weeks of intervention, compared with the db/db-CON group, the percentage of body fat, fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) in the db/db-CGA group were all significantly decreased; TGF-β1 protein expression and AR activity in the kidney were both decreased; and the adiponectin level in visceral adipose was increased. The protein expression of adiponectin receptors (ADPNRs), the phosphorylation of AMP-activated protein kinase (AMPK) in the liver and muscle, and the mRNA and protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) in the liver were all significantly greater. CGA could lower the levels of fasting plasma glucose and HbA1c during late diabetes and improve kidney fibrosis to some extent through the modulation of adiponectin receptor signaling pathways in db/db mice. PMID:25849026

  11. Expression levels of seven candidate genes in human peripheral blood mononuclear cells and their association with preeclampsia

    PubMed Central

    Garza-Veloz, I.; Carrillo-Sanchez, K.; Martinez-Gaytan, V.; Cortes-Flores, R.; Ochoa-Torres, M. A.; Guerrero, G. G.; Rodriguez-Sanchez, I. P.; Cancela-Murrieta, C. O.; Zamudio-Osuna, M.; Badillo-Almaraz, J. I.; Castruita-De la Rosa, C.

    2014-01-01

    Objective To evaluate the peripheral blood mononuclear cell (PBMC) expression levels of hemeoxygenase 1 (HMOX-1), superoxide dismutase 1 (SOD-1), vascular endothelial growth factor A (VEGF-A), transforming growth factor beta 1 (TGF-β1), interleukin (IL)-6, IL-15 and AdipoQ genes to study their association with preeclampsia (PE). Methods A total of 177 pregnant women were recruited: 108 cases and 69 controls. Quantification of gene expression was measured by quantitative real-time polymerase chain reaction (PCR) using TaqMan probes. Results Underexpression of VEGF-A and TGF-β1 was a constant in most of the cases (80.91% and 76.36%, respectively) and their expression was associated with onset and/or severity of disease (p values < 0.05). IL-6, IL-15 and AdipoQ, showed low or no expression in PBMC samples evaluated. Conclusion PBMC underexpression of VEGF-A and TGF-β1 is a hallmark of PE in the study population. PMID:24295154

  12. The Impact of Full-Length, Trimeric and Globular Adiponectin on Lipolysis in Subcutaneous and Visceral Adipocytes of Obese and Non-Obese Women.

    PubMed

    Wedellova, Zuzana; Kovacova, Zuzana; Tencerova, Michaela; Vedral, Tomas; Rossmeislova, Lenka; Siklova-Vitkova, Michaela; Stich, Vladimir; Polak, Jan

    2013-01-01

    Contribution of individual adiponectin isoforms to lipolysis regulation remains unknown. We investigated the impact of full-length, trimeric and globular adiponectin isoforms on spontaneous lipolysis in subcutaneous abdominal (SCAAT) and visceral adipose tissues (VAT) of obese and non-obese subjects. Furthermore, we explored the role of AMPK (5'-AMP-activated protein kinase) in adiponectin-dependent lipolysis regulation and expression of adiponectin receptors type 1 and 2 (AdipoR1 and AdipoR2) in SCAAT and VAT. Primary adipocytes isolated from SCAAT and VAT of obese and non-obese women were incubated with 20 µg/ml of: A) full-length adiponectin (physiological mixture of all adiponectin isoforms), B) trimeric adiponectin isoform or C) globular adiponectin isoform. Glycerol released into media was used as a marker of lipolysis. While full-length adiponectin inhibited lipolysis by 22% in non-obese SCAAT, globular isoform inhibited lipolysis by 27% in obese SCAAT. No effect of either isoform was detected in non-obese VAT, however trimeric isoform inhibited lipolysis by 21% in obese VAT (all p<0.05). Trimeric isoform induced Thr172 p-AMPK in differentiated preadipocytes from a non-obese donor, while globular isoform induced Ser79 p-ACC by 32% (p<0.05) and Ser565 p-HSL by 52% (p = 0.08) in differentiated preadipocytes from an obese donor. AdipoR2 expression was 17% and 37% higher than AdipoR1 in SCAAT of obese and non-obese groups and by 23% higher in VAT of obese subjects (all p<0.05). In conclusion, the anti-lipolytic effect of adiponectin isoforms is modified with obesity: while full-length adiponectin exerts anti-lipolytic action in non-obese SCAAT, globular and trimeric isoforms show anti-lipolytic activity in obese SCAAT and VAT, respectively.

  13. Serum adiponectin in HIV-1 and hepatitis C virus mono- and co-infected Kenyan injection drug users

    PubMed Central

    Ndombi, Eric M; Budambula, Valentine; Webale, Mark K; Musumba, Francis O; Wesongah, Jesca O; Mibei, Erick; Ahmed, Aabid A; Lihana, Raphael; Were, Tom

    2015-01-01

    Adiponectin is an important marker of anthropometric profiles of adipose tissue. However, association of adiponectin and adiposity in HIV mono- and co-infected and hepatitis (HCV) injection drug users (IDUs) has not been elucidated. Therefore, the relationship of total adiponectin levels with anthropometric indices of adiposity was examined in HIV mono-infected (anti-retroviral treatment, ART-naive, n=16 and -experienced, n=34); HCV mono-infected, n=36; HIV and HCV co-infected (ART-naive, n=5 and -experienced, n=13); uninfected, n=19 IDUs; and healthy controls, n=16 from coastal Kenya. Anthropometric indices of adiposity were recorded and total circulating adiponectin levels were measured in serum samples using enzyme-linked immunosorbent assay. Adiponectin levels differed significantly amongst the study groups (P<0.0001). Post-hoc analyses revealed decreased levels in HIV mono-infected ART-naive IDUs in comparison to uninfected IDUs (P<0.05) and healthy controls (P<0.05). However, adiponectin levels were elevated in HCV mono-infected IDUs relative to HIV mono-infected ART-naive (P<0.001) and -experienced (P<0.001) as well as HIV and HCV co-infected ART-naive (P<0.05) IDUs. Furthermore, adiponectin correlated with weight (ρ=0.687; P=0.003) and BMI (ρ=0.598; P=0.014) in HIV mono-infected ART-naive IDUs; waist circumference (ρ=−0.626; P<0.0001), hip (ρ=−0.561; P=0.001) circumference, and bust-to-waist ratio (ρ=0.561; P=0.001) in HIV mono-infected ART-experienced IDUs; waist girth (ρ=0.375; P=0.024) in HCV mono-infected IDUs; and waist-to-hip ratio (ρ=−0.872; P=0.048) in HIV and HCV co-infected ART-naive IDUs. Altogether, these results suggest suppression of adiponectin production in treatment-naive HIV mono-infected IDUs and that circulating adiponectin is a useful surrogate marker of altered adiposity in treatment-naive and -experienced HIV and HCV mono- and co-infected IDUs. PMID:26306727

  14. Cut-Off Value of Total Adiponectin for Managing Risk of Developing Metabolic Syndrome in Male Japanese Workers

    PubMed Central

    Hata, Akiko; Yonemoto, Koji; Shikama, Yosuke; Aki, Nanako; Kosugi, Chisato; Tamura, Ayako; Ichihara, Takako; Minagawa, Takako; Kuwamura, Yumi; Miyoshi, Masashi; Nakao, Takayuki; Funaki, Makoto

    2015-01-01

    Aim To determine the optimal cut-off value of serum total adiponectin for managing the risk of developing metabolic syndrome (MetS) in male Japanese workers. Methods A total of 365 subjects without MetS aged 20–60 years were followed up prospectively for a mean of 3.1 years. The accelerated failure-time model was used to estimate time ratio (TR) and cut-off value for developing MetS. Results During follow-up, 45 subjects developed MetS. Age-adjusted TR significantly declined with decreasing total adiponectin level (≤ 4.9, 5.0–6.6, 6.7–8.8 and ≥ 8.9 μg/ml, P for trend = 0.003). In multivariate analyses, TR of MetS was 0.12 (95% CI 0.02–0.78; P = 0.03) in subjects with total adiponectin level of 5.0–6.6 μg/ml, and 0.15 (95% CI 0.02–0.97; P = 0.047) in subjects with total adiponectin level ≤ 4.9 μg/ml compared with those with total adiponectin level ≥ 8.9 μg/ml. The accelerated failure-time model showed that the optimal cut-off value of total adiponectin for managing the risk of developing MetS was 6.2 μg/ml. In the multivariate-adjusted model, the mean time to the development of MetS was 78% shorter for total adiponectin level ≤ 6.2 μg/ml compared with > 6.2 μg/ml (TR 0.22, 95% CI: 0.08–0.64, P = 0.005). Conclusion Our findings suggest that the cut-off value for managing the risk of developing MetS is 6.2 μg/ml in male Japanese workers. Subjects with total adiponectin level ≤ 6.2 μg/ml developed MetS more rapidly than did those with total adiponectin level > 6.2 μg/ml. PMID:25705909

  15. Adiponectin Regulates the Polarization and Function of Microglia via PPAR-γ Signaling Under Amyloid β Toxicity

    PubMed Central

    Song, Juhyun; Choi, Seong-Min; Kim, Byeong C.

    2017-01-01

    Alzheimer’s disease (AD), characterized by the abnormal accumulation of amyloid beta (Aβ), is gradually increasing globally. Given that AD is considered a neuroinflammatory disease, recent studies have focused on the cellular mechanisms in brain inflammatory conditions that underlie AD neuropathology. Microglia are macrophage cells in the central nervous system (CNS) that are activated in response to Aβ condition. The function of microglia contributes to the neuroinflammation in AD brain, suggesting that microglia regulate the production of inflammatory mediators and contribute to the regeneration of damaged tissues. Adiponectin, an adipokine derived from adipose tissue, has been known to regulate inflammation and control macrophages during oxidative stress conditions. In present study, we investigated whether adiponectin influences the polarization and function of microglia under Aβ toxicity by examining alterations of BV2 microglia function and polarization by Acrp30 (a globular form of adiponectin) treatment using reverse transcription PCR, western blotting and immunofluorescence staining. Acrp30 promoted the induction of the M2 phenotype, and regulated the inflammatory responses through peroxisome proliferator-activated receptor (PPAR)-γ signaling under Aβ toxicity. In addition, Acrp30 boosted the capacity of Aβ scavenging in microglia. Taken together, we suggest that adiponectin may control the function of microglia by promoting anti-inflammatory responses through PPAR- γ signaling. Hence, we conclude that adiponectin may act as a critical controller of microglia function in the AD brain. PMID:28326017

  16. Associations between perinatal factors and adiponectin and leptin in 9-year-old Mexican-American children

    PubMed Central

    Volberg, Vitaly; Harley, Kim G.; Aguilar, Raul S.; Rosas, Lisa G.; Huen, Karen; Yousefi, Paul; Davé, Veronica; Phan, Nguyet; Lustig, Robert H.; Eskenazi, Brenda; Holland, Nina

    2012-01-01

    Objectives To 1) determine whether perinatal factors (including maternal anthropometry and nutrition and early life growth measures) are associated with adiponectin and leptin levels in 9-year-old children, and 2) assess relationships between adiponectin, leptin and concurrent lipid profile in these children. Methods We measured plasma adiponectin and leptin for 146 mother - 9-year-old child pairs from the ongoing longitudinal birth cohort followed by the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS). Data on perinatal factors, including sociodemographics, maternal anthropometry and nutrition, and early life child growth were collected during pregnancy, birth and 6-month visits. Results Greater rate of weight and length gain during the first 6 months of life were associated with lower adiponectin in 9-year-olds (β=−2.0, P=0.04; β=−8.2, P=0.02, respectively) adjusting for child BMI. We found no associations between child adipokine levels and either maternal calorie, protein, total fat, saturated fat, fiber, sugar-sweetened beverage consumption during pregnancy or children’s concurrent sugar-sweetened beverage and fast food intake. Lipid profile in 9-year-old children closely reflected adiponectin but not leptin levels after adjustment for child BMI. Additionally, we report that child adipokine levels were closely related to their mothers’ levels at the 9-year-visit. Conclusion Overall, our results support the hypothesis that early life factors may contribute to altered adipokine levels in children. PMID:23325579

  17. Adiponectin inhibits neutrophil apoptosis via activation of AMP kinase, PKB and ERK 1/2 MAP kinase.

    PubMed

    Rossi, Alessandra; Lord, Janet M

    2013-12-01

    Neutrophils are abundant, short-lived leukocytes that play a key role in the immune defense against microbial infections. These cells die by apoptosis following activation and uptake of microbes and will also enter apoptosis spontaneously at the end of their lifespan if they do not encounter a pathogen. Adiponectin exerts anti-inflammatory effects on neutrophil antimicrobial functions, but whether this abundant adipokine influences neutrophil apoptosis is unknown. Here we report that adiponectin in the physiological range (1-10 μg/ml) reduced apoptosis in resting neutrophils, decreasing caspase-3 cleavage and maintaining Mcl-1 expression by stabilizing this anti-apoptotic protein. We show that adiponectin induced phosphorylation of AMP-activated kinase (AMPK), protein kinase B (PKB), extracellular signal-regulated kinase (ERK 1/2) and p38 mitogen activated protein kinase (MAPK). Pharmacological inhibition of AMPK, PKB and ERK 1/2 ablated the pro-survival effects of adiponectin and treatment of neutrophils with an AMPK specific activator (AICAR) and AMPK inhibitor (compound C) respectively decreased and increased apoptosis. Finally, activation of AMPK by AICAR or adiponectin also decreased ceramide accumulation in the neutrophil cell membrane, a process involved in the early stages of spontaneous apoptosis, giving another possible mechanism downstream of AMPK activation for the inhibition of neutrophil apoptosis.

  18. Adiponectin levels in south Indian children with type 1 diabetes mellitus and nondiabetic children and its correlation with anthropometry and glycemic control.

    PubMed

    Solomon, J Ritchie Sharon; Varadarajan, Poovazhagi; Varadarajan, V Poovazhagi

    2013-09-01

    Studies have reported high adiponectin levels in children with type 1 diabetes mellitus (T1DM). Adiponectin has been found to have anti-atherogenic action and other protective functions. We wanted to estimate adiponectin level in south Indian T1DM children and compare it with that of non-diabetic children and study its correlation with anthropometry and glycemic status. Sixty children with T1DM and forty non-diabetic children of age less than 15 years were analysed. Mean adiponectin level was higher in T1DM group than in non diabetic group (p < 0.001) irrespective of the age group or sex. Negative correlation was observed between SFT- triceps and adiponectin in diabetic and control group. Multiple regression coefficient analysis of various parameters showed SFT- triceps as a statistically significant predictor of adiponectin level (p = 0.001). We conclude that, children with T1DM had higher adiponectin level than non-diabetic children. Low SFT- triceps measuremet may be a predictor of higher adiponectin level.

  19. Pro-insulin, C peptide, glucagon, adiponectin, TNF alpha, AMPK: neglected players in type 2 diabetes mellitus.

    PubMed

    Lele, R D

    2010-01-01

    This article emphasizes (1) the utility of routine measurement of pro-insulin to insulin ratio as a specific marker of insulin resistance and predictor of future T2DM, HT and CAD, (2) routine C-Peptide estimation to determine which T2DM needs insulin and to monitor the effect of newer drugs which promote beta cell regeneration, (3) routine estimation of adiponectin and TNF alpha and monitor response to thiozolidine drugs which increases adiponectin and decreases TNF alpha production by adipocytes, (4) crucial role of AMPK--Cellular energy sensor in mediating the beneficial effects of exercise as well as drugs (adiponectin, metformin) in T2DM, (5) Availability of glucogon suppressors will eliminate the need for giving insulin to T2 DM with normal C Pepetide levels which inevitably causes undesirable weight gain & hypoglycemia.

  20. Citrus auraptene acts as an agonist for PPARs and enhances adiponectin production and MCP-1 reduction in 3T3-L1 adipocytes

    SciTech Connect

    Kuroyanagi, Kayo; Kang, Min-Sook; Goto, Tsuyoshi; Hirai, Shizuka; Ohyama, Kana; Kusudo, Tatsuya; Yu, Rina; Yano, Masamichi; Sasaki, Takao; Takahashi, Nobuyuki; Kawada, Teruo

    2008-02-01

    Citrus fruit compounds have many health-enhancing effects. In this study, using a luciferase ligand assay system, we showed that citrus auraptene activates peroxisome proliferator-activated receptor (PPAR)-{alpha} and PPAR{gamma}. Auraptene induced up-regulation of adiponectin expression and increased the ratio of the amount of high-molecular-weight multimers of adiponectin to the total adiponectin. In contrast, auraptene suppressed monocyte chemoattractant protein (MCP)-1 expression in 3T3-L1 adipocytes. Experiments using PPAR{gamma} antagonist demonstrated that these effects on regulation of adiponectin and MCP-1 expression were caused by PPAR{gamma} activations. The results indicate that auraptene activates PPAR{gamma} in adipocytes to control adipocytekines such as adiponectin and MCP-1 and suggest that the consumption of citrus fruits, which contain auraptene can lead to a partial prevention of lipid and glucose metabolism abnormalities.

  1. In contrast to matrix metalloproteinases, serum adiponectin concentrations increase after radioiodine treatment of thyrotoxicosis

    PubMed Central

    2012-01-01

    Background Matrix metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), remodel extracellular matrix under physiological and pathological conditions and are implicated in pathogenesis of cardiovascular diseases, cancer and in chronic inflammation. We have endeavoured to assess whether concentrations of MMPs, TIMPs, and anti-inflammatory adiponectin are altered by pharmacological treatment of acute thyrotoxicosis or by radioiodine therapy (RIT). Material and methods We measured serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, and adiponectin, TSH, free T4 (FT4) and free T3 (FT3) in 15 patients (4 males), age (years) 51.8±15.3 (mean±SD) with hyperthyroidism treated with thiamazole (Group 1) and in 20 subjects (2 males), treated for thyrotoxicosis with radioiodine, age 52.3±12.4 (Group 2), where blood samples were taken before RIT, visit 1 (V1), seven days post RIT, visit 2 (V2), and two to three months post RIT, visit 3 (V3). Results In Group 1 there was no significant change in concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2 or adiponectin, despite a fall in FT4 and FT3 (8.74±4.79 pg/ml vs 3.54±2.40 pg/ml, for FT3, and 4.48 ±2.21 ng/ml vs 1.02±1.07 ng/ml, for FT4, p<0.001). In Group 2 RIT did not cause any acute change in serum MMP-2, MMP-9, TIMP-1 and TIMP-2 or adiponectin (V1 vs V2). However, there was a significant increase in serum adiponectin [from 15201±8860 ng/ml (V1) to 19373±8657 ng/ml (at V3), p<0.05], and TIMP-2 at V3 [from 129±45 ng/ml (V1) to 149±38 ng/ml (V3), p<0.01]. There was no significant change MMP-2, MMP-9 and TIMP-1 between V1 and V3. There was a decrease in FT4 and FT3 from 24.4±15.4 pmol/l (V1) to 14.7±10.6 pmol/l (V3), and from 10.0±5.65 (V1) to 6.1±4.8 pmol/l (V2), p<0.01, for FT4 and FT3, respectively. Conclusions Radioiodine therapy of thyrotoxicosis does not alter serum MMP-2, MMP-9 or TIMP-1 concentrations either acutely or after about three months of observation. An increase in serum adiponectin

  2. Profile of leptin, adiponectin, and body fat in patients with hyperprolactinemia: Response to treatment with cabergoline

    PubMed Central

    Pala, Nazir Ahmad; Laway, Bashir Ahmad; Misgar, Raiz Ahmad; Shah, Zaffar Amin; Gojwari, Tariq A.; Dar, Tariq A.

    2016-01-01

    Introduction: Though hypoadiponectinemia and leptin resistance have been proposed as potential factors for weight gain in patients with hyperprolactinemia (HPL), the effects of HPL and cabergoline on these adipocyte-derived hormones are not clear. Aims of this study were (i) to assess the alterations of body fat, leptin, and adiponectin in patients with HPL (ii) effect of cabergoline treatment on these parameters. Methods: Nineteen consecutive patients with prolactinoma (median prolactin [PRL] 118.6 (interquartile range: 105.3) μg/L) and 20 controls were studied in a nonrandomized matched prospective design. The controls were age, gender, and body mass index (BMI) matched. Anthropometric data, metabolic variables, leptin, and adiponectin were studied at baseline and 3 and 6 months after cabergoline treatment. Results: Patients with prolactinoma had increased level of fasting plasma glucose (P < 0.001) as compared to age-, gender-, and BMI-matched healthy controls. Estradiol concentration of controls was higher than that of patients (P = 0.018). Patients with prolactinoma had higher levels of leptin (P = 0.027) as compared to healthy controls without a significant difference in adiponectin levels. There was a significant decrease of body weight at 3 months (P = 0.029), with a further decline at 6 months (P < 0.001) of cabergoline therapy. Furthermore, there was a significant decrement of BMI (P < 0.001), waist circumference (P = 0.003), waist-hip ratio (P = 0.03), total body fat (P = 0.003), plasma glucose (P < 0.001), leptin levels (P = 0.013), and an increase in estradiol concentration (P = 0.03) at 6 months of cabergoline treatment. Conclusion: Patients with prolactinoma have adverse metabolic profile compared to matched controls. Normalization of PRL with cabergoline corrects all the metabolic abnormalities. PMID:27042412

  3. Enhanced nutrition improves growth and increases blood adiponectin concentrations in very low birth weight infants

    PubMed Central

    Blakstad, Elin W.; Moltu, Sissel J.; Nakstad, Britt; Veierød, Marit B.; Strømmen, Kenneth; Júlíusson, Pétur B.; Almaas, Astrid N.; Rønnestad, Arild E.; Brække, Kristin; Drevon, Christian A.; Iversen, Per O.

    2016-01-01

    Background Adequate nutrient supply is essential for optimal postnatal growth in very low birth weight (VLBW, birth weight<1,500 g) infants. Early growth may influence the risk of metabolic syndrome later in life. Objective To evaluate growth and blood metabolic markers (adiponectin, leptin, and insulin-like growth factor-1 (IGF-1)) in VLBW infants participating in a randomized nutritional intervention study. Design Fifty VLBW infants were randomized to an enhanced nutrient supply or a standard nutrient supply. Thirty-seven infants were evaluated with growth measurements until 2 years corrected age (CA). Metabolic markers were measured at birth and 5 months CA. Results Weight gain and head growth were different in the two groups from birth to 2 years CA (weight gain: pinteraction=0.006; head growth: pinteraction=0.002). The intervention group improved their growth z-scores after birth, whereas the control group had a pronounced decline, followed by an increase and caught up with the intervention group after discharge. At 5 months CA, adiponectin concentrations were higher in the intervention group and correlated with weight gain before term (r=0.35) and nutrient supply (0.35≤r≤0.45). Leptin concentrations correlated with weight gain after term and IGF-1 concentrations with length growth before and after term and head growth after term (0.36≤r≤0.53). Conclusion Enhanced nutrient supply improved early postnatal growth and may have prevented rapid catch-up growth later in infancy. Adiponectin concentration at 5 months CA was higher in the intervention group and correlated positively with early weight gain and nutrient supply. Early nutrition and growth may affect metabolic markers in infancy. Clinical Trial Registration (ClinicalTrials.gov) no.: NCT01103219 PMID:27914187

  4. Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes

    SciTech Connect

    Chen Baoying; Lam, Karen S.L.; Wang Yu; Wu Donghai; Lam, Michael C.; Shen Jiangang; Wong Laiching; Hoo, Ruby L.C.; Zhang Jialiang; Xu Aimin . E-mail: amxu@hkucc.hku.hk

    2006-03-10

    Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease. However, the mechanism that mediates the aberrant production of these two adipokines in obesity remains poorly understood. In this study, we investigated the effects of hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient hypoxia markedly suppressed adiponectin mRNA expression and its protein secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1{alpha} (HIF-1{alpha}), mimicked the hypoxia-mediated modulations of these two adipokines. Hypoxia caused a modest elevation of ROS in adipocytes. However, ablation of intracellular ROS by antioxidants failed to alleviate hypoxia-induced aberrant production of adiponectin and PAI-1. On the other hand, the antioxidants could reverse hydrogen peroxide (H{sub 2}O{sub 2})-induced dysregulation of adiponectin and PAI-1 production. H{sub 2}O{sub 2} treatment decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPAR{gamma}) and CCAAT/enhancer binding protein (C/EBP{alpha}), but had no effect on HIF-1{alpha}, whereas hypoxia stabilized HIF-1{alpha} and decreased expression of C/EBP{alpha}, but not PPAR{gamma}. Taken together, these data suggest that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression in adipocytes via distinct signaling pathways. These effects may contribute to hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes, and cardiovascular diseases.

  5. Relationship between epicardial adipose tissue, coronary artery disease and adiponectin in a Mexican population

    PubMed Central

    2014-01-01

    Background The amount of epicardial adipose tissue (EAT) around the heart has been identified as an independent predictor of coronary artery disease (CAD), potentially through local release of inflammatory cytokines. Ethnic differences have been observed, but no studies have investigated this relationship in the Mexican population. The objective of the present study was to evaluate whether a relationship exist between EAT thickness assessed via echocardiography with CAD and adiponectin levels in a Mexican population. Methods We studied 153 consecutive patients who underwent coronary angiography and transthoracic echocardiography (TTE). EAT thickness on the free wall of the right ventricle was measured at the end of systole from parasternal long and short axis views of three consecutive cardiac cycles. Coronary angiograms were analyzed for the presence, extent and severity of CAD. Serum adiponectin, lipids, glucose, C-reactive protein and fibrinogen were determined. Results EAT thickness was greater in patients with CAD than in those without CAD from both parasternal long (5.39 ± 1.75 mm vs 4.00 ± 1.67 mm p < 0.0001) and short-axis views (5.23 ± 1.67 vs 4.12 ± 1.77, p = 0.001). EAT thickness measured from parasternal long and short-axis showed a statistically significant positive correlation with age (r = 0.354, p < 0.001; r = 0.286, p < 0.001 respectively), and waist circumference (r = 0.189, p = 0.019; r = 0.217, p = 0.007 respectively). A significant negative correlation between EAT thickness from the parasternal long axis with cholesterol-HDL was observed (r = -0.163, p = 0.045). No significant correlation was found between epicardial fat thickness and serum adiponectin or with the severity of CAD. Conclusions EAT thickness was greater in patients with CAD. However, no correlation was observed with the severity of the disease or with serum adiponectin levels. EAT thickness measured by

  6. Adiponectin, orexin A and orexin B concentrations in the serum and uterine luminal fluid during early pregnancy of pigs.

    PubMed

    Smolinska, Nina; Kiezun, Marta; Dobrzyn, Kamil; Szeszko, Karol; Maleszka, Anna; Kaminski, Tadeusz

    2017-03-01

    Adiponectin is the most abundant adipose-released protein that circulates in human plasma at high concentrations. The neuropeptides orexin A (OXA, hypocretin-1) and orexin B (OXB, hypocretin-2) are derived from a common precursor peptide, prepro-orexin and are produced mainly by neurons located in the lateral hypothalamus. It has been demonstrated that the peptides such as adiponectin and orexins have an important role in the regulation of energy metabolism and neuroendocrine functions. These hormones appear to be implicated in both normal and disturbed pregnancy. The objectives of this study were to determine adiponectin and orexin concentrations in the plasma and uterine luminal fluid (ULF) of pigs during early gestation and to explore the relationships between hormone concentrations and stages of pregnancy. The greatest plasma concentrations of adiponectin were observed on days 15-16 and 27-28 of pregnancy, and the least concentrations were on days 30-32 of gestation and on days 10-11 of the oestrous cycle. In ULF, adiponectin concentrations were greater on days 15-16 of pregnancy and on days 10-11 of the oestrous cycle than on days 10-11 and days 12-13 of pregnancy. The greatest OXA concentrations in the blood plasma were noted on days 10-16 of gestation, and the least OXA concentrations were on days 27-32 of pregnancy and on days 10-11 of the oestrous cycle. Orexin A concentrations in ULF were greater on days 10-11 of the cycle than throughout pregnancy. Serum OXB concentrations were greatest on days 10-11 and 30-32 of pregnancy, and least on days 12-28 of gestation. The greatest OXB concentrations in ULF were on days 10-13 of gestation, and the least OXB concentrations were on days 15-16 of pregnancy. This is first study to demonstrate the presence of adiponectin and orexins in the serum and ULF during early pregnancy of pigs as well as the relationships between adiponectin and orexin concentrations and the stage of pregnancy. The fluctuations in adiponectin

  7. Globular adiponectin elicits neuroprotection by inhibiting NADPH oxidase-mediated oxidative damage in ischemic stroke.

    PubMed

    Song, W; Huo, T; Guo, F; Wang, H; Wei, H; Yang, Q; Dong, H; Wang, Q; Xiong, L

    2013-09-17

    Recent studies indicate that adiponectin can attenuate cerebral ischemic lesions via its functional area located in the C-terminal globular domain, which is called globular adiponectin (gAD). However, the mechanisms underlying this action remain unclear. In this study, we investigated the antioxidant properties of gAD during cerebral ischemia. Adult male C57BL/6 mice received an intracerebral injection of gAD with or without tetrabromocinnamic acid (TBCA, a NADPH oxidase activator). Mice were subjected to middle cerebral artery occlusion (MCAO) after gAD injection. Infarct volume, neurological function, the activity of antioxidant enzymes (superoxide dismutase [SOD], catalase), the content of malondialdehyde (MDA), and the expression of Bax, Bcl-2, cleaved caspase-3 and NADPH oxidase 2 (NOX2) were examined at 24h after MCAO. Infarct volume was attenuated in gAD-transduced mice when compared with mice in the MCAO group, with significant improvement in neurological function. In addition, neuronal apoptosis was attenuated, along with the expression of Bax/Bcl-2 and cleaved caspase 3. Furthermore, the activities of SOD and catalase increased, and the content of MDA reduced. However, TBCA blocked the effect of gAD on cerebral protection and its antioxidant abilities. Taken together, these results demonstrate that the neuroprotective action of gAD may result from the promotion of antioxidant capacity by inhibiting the NOX2 signaling system.

  8. Globular adiponectin controls insulin-mediated vasoreactivity in muscle through AMPKα2.

    PubMed

    de Boer, Michiel P; Meijer, Rick I; Richter, Erik A; van Nieuw Amerongen, Geerten P; Sipkema, Pieter; van Poelgeest, Erik M; Aman, Jurjan; Kokhuis, Tom J A; Koolwijk, Pieter; van Hinsbergh, Victor W M; Smulders, Yvo M; Serné, Erik H; Eringa, Etto C

    2016-03-01

    Decreased tissue perfusion increases the risk of developing insulin resistance and cardiovascular disease in obesity, and decreased levels of globular adiponectin (gAdn) have been proposed to contribute to this risk. We hypothesized that gAdn controls insulin's vasoactive effects through AMP-activated protein kinase (AMPK), specifically its α2 subunit, and studied the mechanisms involved. In healthy volunteers, we found that decreased plasma gAdn levels in obese subjects associate with insulin resistance and reduced capillary perfusion during hyperinsulinemia. In cultured human microvascular endothelial cells (HMEC), gAdn increased AMPK activity. In isolated muscle resistance arteries gAdn uncovered insulin-induced vasodilation by selectively inhibiting insulin-induced activation of ERK1/2, and the AMPK inhibitor compound C as well as genetic deletion of AMPKα2 blunted insulin-induced vasodilation. In HMEC deletion of AMPKα2 abolished insulin-induced Ser(1177) phosphorylation of eNOS. In mice we confirmed that AMPKα2 deficiency decreases insulin sensitivity, and this was accompanied by decreased muscle microvascular blood volume during hyperinsulinemia in vivo. This impairment was accompanied by a decrease in arterial Ser(1177) phosphorylation of eNOS, which closely related to AMPK activity. In conclusion, globular adiponectin controls muscle perfusion during hyperinsulinemia through AMPKα2, which determines the balance between NO and ET-1 activity in muscle resistance arteries. Our findings provide a novel mechanism linking reduced gAdn-AMPK signaling to insulin resistance and impaired organ perfusion.

  9. Chronic Kidney Disease, Obesity, and Hypertension: The Role of Leptin and Adiponectin

    PubMed Central

    Tesauro, M.; Mascali, A.; Franzese, O.; Cipriani, S.; Cardillo, C.; Di Daniele, N.

    2012-01-01

    Chronic kidney disease is a major public health problem and characterized by a progressive loss in renal function over a period of months or years as defined by structural or functional abnormalities of the kidney. Several elements contribute to determine a progression of the kidney injury, inducing a worsening of renal damage and accelerating the decline of renal function: obesity and hypertension are two known factors of kidney progression. Remarkable improvements have been recently achieved in the study of the endocrine features of the adipose tissue and have been able to produce hormone-like peptides named adipokines or adipocytokines. Among these adipocytokines, which represent a link between obesity, hypertension, and chronic nephropathy, leptins and adiponectin appear to play an important role. Leptin not only is a prohypertension element (renal progression factor) through the activation sympathetic nervous, but also is able to induce prosclerotic effects directly on the kidney. In contrast, a decline of adiponectin levels has been shown to be related to a picture of hypertension: an endothelial dysfunction has been described as the main pathogenic mechanism responsible for this phenomenon. PMID:23320148

  10. Temporal Changes in Gene Expression Profile during Mature Adipocyte Dedifferentiation

    PubMed Central

    Côté, Julie Anne; Guénard, Frédéric; Lessard, Julie; Lapointe, Marc; Biron, Simon

    2017-01-01

    Objective. To characterize changes in gene expression profile during human mature adipocyte dedifferentiation in ceiling culture. Methods. Subcutaneous (SC) and omental (OM) adipose tissue samples were obtained from 4 participants paired for age and BMI. Isolated adipocytes were dedifferentiated in ceiling culture. Gene expression analysis at days 0, 4, 7, and 12 of the cultures was performed using Affymetrix Human Gene 2.0 STvi arrays. Hierarchical clustering according to similarity of expression changes was used to identify overrepresented functions. Results. Four clusters gathered genes with similar expression between day 4 to day 7 but decreasing expression from day 7 to day 12. Most of these genes coded for proteins involved in adipocyte functions (LIPE, PLIN1, DGAT2, PNPLA2, ADIPOQ, CEBPA, LPL, FABP4, SCD, INSR, and LEP). Expression of several genes coding for proteins implicated in cellular proliferation and growth or cell cycle increased significantly from day 7 to day 12 (WNT5A, KITLG, and FGF5). Genes coding for extracellular matrix proteins were differentially expressed between days 0, 4, 7, and 12 (COL1A1, COL1A2, and COL6A3, MMP1, and TGFB1). Conclusion. Dedifferentiation is associated with downregulation of transcripts encoding proteins involved in mature adipocyte functions and upregulation of genes involved in matrix remodeling, cellular development, and cell cycle.

  11. Adiponectin, Leptin, and Chemerin in Elderly Patients with Type 2 Diabetes Mellitus: A Close Linkage with Obesity and Length of the Disease

    PubMed Central

    Brandão Proença, Jorge; Neuparth, Maria João

    2014-01-01

    Obesity, insulin resistance, and aging are closely associated and adipokines seem to have a crucial role in their pathophysiology. We aim to study the relationship between aging and chemerin, adiponectin, and leptin levels in type 2 diabetes mellitus (T2DM). Age correlated positively with chemerin and leptin and inversely with adiponectin. Body mass index (BMI) correlated positively with leptin (in males) and chemerin and inversely with adiponectin. The patients with ≥65 years (n = 34) showed significantly higher leptin and chemerin and lower adiponectin levels than middle-aged (38–64 years) patients (n = 39) and controls (n = 20). After statistical adjustment for length of disease, there was a loss of significance, between T2DM groups, for adiponectin and, in female, for leptin. In the older group, BMI correlated with adiponectin and with leptin, but not with chemerin. Adiponectin and leptin levels in elderly T2DM patients seem to be closely linked to obesity and to length of the disease. In elderly T2DM patients, chemerin concentrations are increased and seem to be independent of length of disease and BMI, suggesting that adipocyte dysfunction is enhanced with aging. The understanding of the glucose homeostasis impairment in the elderly is mandatory in order to achieve ways to improve their quality of life and longevity. PMID:25105135

  12. Serum Zinc and Adiponectin Levels in Patients with Polycystic Ovary Syndrome, Adjusted for Anthropometric, Biochemical, Dietary Intake, and Physical Activity Measures.

    PubMed

    Mazloomi, Sahar; Alizadeh, Narges; Aminzare, Majid; Niroomand, Soudabeh; Mousavi, Seyedeh Neda

    2017-02-03

    Previous studies have shown that serum zinc and adiponectin levels are associated with insulin resistance in the polycystic ovary syndrome (PCOS) patients. But there is no study to evaluate serum zinc and adiponectin levels as predictor markers of PCOS, adjusted for anthropometric, biochemical, dietary intake, and physical activity measures. Ninety-one new PCOS cases (based on the Rotterdam criteria) and 85 healthy control women participated and individually matched based on age. Food intake of all participants obtained by the food frequency and physical activity level was assessed by the International Physical Activity Questionnaires. Serum glucose, lipid profile, androgens, insulin, adiponectin, and zinc concentrations were measured at the fasting state. Weight, BMI, waist circumference, and body fat, as well as serum levels of DHEAS, insulin, TG, LDL cholesterol (LDL.C), homeostasis model assessment of insulin resistance (HOMA-IR), and LH/FSH ratio, were significantly higher in the PCOS compared with those of the healthy control women. Serum levels of zinc and adiponectin were significantly lower in the PCOS than those of the healthy control women. Results of the logistic regression model showed significant effects of adiponectin, zinc, and LH/FSH ratio on the PCOS, adjusted for anthropometric and biochemical measures (p < 0.05). In the present study, serum level of zinc had significant correlation with adiponectin in the PCOS patients, and serum levels of zinc, adiponectin, and LH/FSH ratio had significant effects on the PCOS occurrence.

  13. Dietary Supplementation with ω-3 PUFA Increases Adiponectin and Attenuates Ventricular Remodeling and Dysfunction with Pressure Overload

    PubMed Central

    Duda, Monika K.; O'Shea, Karen M.; Lei, Biao; Barrows, Brian R.; Azimzadeh, Agnes M.; McElfresh, Tracy E.; Hoit, Brian D.; Kop, Willem J.; Stanley, William C.

    2009-01-01

    Objective Epidemiological studies suggest that consumption of ω-3 polyunsaturated fatty acids (ω-3 PUFA) decreases the risk of heart failure. We assessed the effects of dietary supplementation with ω-3 PUFA from fish oil on the response of the left ventricle (LV) to arterial pressure overload. Methods Male Wistar rats were fed a standard chow or a ω-3 PUFA-supplemented diet. After 1 week rats underwent abdominal aortic banding or sham surgery (n=9-12/group). LV function was assessed by echocardiography after 8 weeks. In addition, we studied the effect of ω-3 PUFA on the cardioprotective adipocyte-derived hormone adiponectin, which may alter the pro-growth serine-threonine kinase Akt. Results Banding increased LV mass to a greater extent with the standard chow (31%) than with ω-3 PUFA (18%). LV end diastolic and systolic volumes were increased by 19% and 105% with standard chow, respectively, but were unchanged with ω-3 PUFA. The expression of adiponectin was up-regulated in adipose tissue, and the plasma adiponectin concentration was significantly elevated. Treatment with ω-3 PUFA increased total Akt protein expression in the heart, but decreased the fraction of Akt in the active phosphorylated form, and thus did not alter the amount of active phospho-Akt. Conclusion Dietary supplementation with ω-3 PUFA attenuated pressure overload-induced LV dysfunction, which was associated with elevated plasma adiponectin. PMID:17643403

  14. Body Composition and Circulating High-Molecular-Weight Adiponectin and IGF-I in Infants Born Small for Gestational Age

    PubMed Central

    de Zegher, Francis; Sebastiani, Giorgia; Diaz, Marta; Sánchez-Infantes, David; Lopez-Bermejo, Abel; Ibáñez, Lourdes

    2012-01-01

    Prenatal growth restraint, if followed by postnatal overweight, confers risk for adult disease including diabetes. The mechanisms whereby neonatal nutrition may modulate such risk are poorly understood. We studied the effects of nutrition (breast-feeding [BRF] vs. formula-feeding [FOF]) on weight partitioning and endocrine state (as judged by high-molecular-weight [HMW] adiponectin and IGF-I) of infants born small for gestational age (SGA). Body composition (by absorptiometry), HMW adiponectin, and IGF-I were assessed at birth and 4 months in BRF infants born appropriate for gestational age (AGA; n = 72) and SGA infants receiving BRF (n = 46) or FOF (n = 56), the latter being randomized to receive a standard (FOF1) or protein-rich formula (FOF2). Compared with AGA-BRF infants, the catchup growth of SGA infants was confined to lean mass, independently of nutrition. Compared with AGA-BRF infants, SGA-BRF infants had normal HMW adiponectin and IGF-I levels at 4 months, whereas SGA-FOF infants had elevated levels of HMW adiponectin (particularly SGA-FOF1) and IGF-I (particularly SGA-FOF2). In conclusion, neonatal nutrition seems to influence endocrinology more readily than body composition of SGA infants. Follow-up will disclose whether the endocrine abnormalities in SGA-FOF infants can serve as early markers of an unfavorable metabolic course and whether they may contribute to design early interventions that prevent subsequent disease, including diabetes. PMID:22648385

  15. Serum Adiponectin and Leptin Concentrations in Relation to Body Fat Distribution, Hematological Indices and Lipid Profile in Humans.

    PubMed

    Lubkowska, Anna; Radecka, Aleksandra; Bryczkowska, Iwona; Rotter, Iwona; Laszczyńska, Maria; Dudzińska, Wioleta

    2015-09-14

    The purpose of the study was to evaluate the relationship between serum adiponectin and leptin concentrations and body composition, hematological indices and lipid profile parameters in adults. The study involved 95 volunteers (BMI from 23.3 to 53 kg/m²). Anthropometric parameters were measured: body weight and height, waist and hip circumference, waist-to-hip ratio, body fat mass (BMF), subcutaneous and visceral fat mass (SFM, VFM), lean body mass (LBM), skeletal muscle mass (SMM). In serum we determined adiponectin and leptin concentrations, extracellular hemoglobin, total bilirubin, as well as lipid metabolism (TCh, HDL-Ch, LDL-Ch, TG). Mean adipokine levels were significantly higher in women (p ≤ 0.01), adiponectin significantly negatively correlated with body height and weight, systolic blood pressure and absolute LBM and SMM values. The same relation was observed for erythroid system indicators and lipid indicators. A positive correlation was exceptionally found between adiponectin and HDL-Ch. LEP negatively correlated with some percentage rates (%LBM, %SMM). Only in women, we observed a positive correlation between LEP and body weight, BMI and WHR. Studies on ADPN and the ADPN/LEP ratio as a valuable complementary diagnostic element in the prediction and prevention of cardiovascular diseases need to be continued.

  16. Lipidomic analysis of the liver identifies changes of major and minor lipid species in adiponectin deficient mice

    PubMed Central

    Wanninger, Josef; Liebisch, Gerhard; Schmitz, Gerd; Bauer, Sabrina; Eisinger, Kristina; Neumeier, Markus; Ouchi, Noriyuki; Walsh, Kenneth; Buechler, Christa

    2014-01-01

    Adiponectin protects from hepatic fat storage but adiponectin deficient mice (APN−/−) fed a standard chow do not develop liver steatosis. This indicates that other pathways might be activated to compensate for adiponectin deficiency. An unbiased and comprehensive screen was performed to identify hepatic alterations of lipid classes in these mice. APN−/− mice had decreased hepatic cholesteryl esters while active SREBP2 and systemic total cholesterol were not altered. Upregulation of cytochromes for bile acid synthesis suggests enhanced biliary cholesterol excretion. Analysis of 37 individual fatty acid species showed reduced stearate whereas total fatty acids were not altered. Total amount of triglycerides and phospholipids were equally abundant. A selective increase of monounsaturated phosphatidylcholine and phosphatidylethanolamine which positively correlate with hepatic and systemic triglycerides with the latter being elevated in APN−/− mice, was identified. Stearoyl-CoA desaturase 1 (SCD1) is involved in the synthesis of monounsaturated fatty acids and despite higher mRNA expression enzyme activity was not enhanced. Glucosylceramide postulated to contribute to liver damage was decreased. This study demonstrates that adiponectin deficiency is associated with hepatic changes in lipid classes in mice fed a standard chow which may protect from liver steatosis. PMID:22465357

  17. Effect of L-arginine supplementation on insulin resistance and serum adiponectin concentration in rats with fat diet

    PubMed Central

    Miczke, Anna; Suliburska, Joanna; Pupek-Musialik, Danuta; Ostrowska, Lucyna; Jabłecka, Anna; Krejpcio, Zbigniew; Skrypnik, Damian; Bogdański, Paweł

    2015-01-01

    Object: The purpose of this study was to determine whether supplementation with L-arginine, a substrate used in the production of nitric oxide, had an effect on adiponectin concentration in rats fed a high-fat diet. The influence of L-arginine on insulin resistance was also evaluated. Materials and methods: The experiment was performed using 36 Wistar rats divided into three groups: group 1 was fed a standard diet, group 2 a high-fat (HF) diet, group 3 a HF diet supplemented with L-arginine. After 42 days, serum levels of lipids, glucose, insulin, NO, and adiponectin were measured. Insulin resistance (IR) was estimated by the Homeostasis Model Assessment (HOMA). Results: Body mass was equal in all 3 groups, at the beginning as well as at the end of the study, however, in group 2 the amount of visceral fat was greater after 42 days. In group 3, there was a tendency for visceral fat to decrease. An increase in cholesterol, triglycerides, insulin and HOMA-IR, as well as a decrease in NO and adiponectin were seen in group 2, while in group 3, L-arginine supplementation ameliorated these disturbances. Conclusions: Our study shows that L-arginine supplementation in rats fed a HF diet is associated with an increase in insulin sensitivity. Our findings suggest that the underlying mechanism could be at least partially related to an increase in adiponectin concentration. PMID:26379826

  18. The Effect of Vegan Protein-Based Diets on Metabolic Parameters, Expressions of Adiponectin and Its Receptors in Wistar Rats.

    PubMed

    Chen, Jie-Hua; Song, Jia; Chen, Yan; Ding, Qiang; Peng, Anfang; Mao, Limei

    2016-10-18

    Vegan protein-based diet has attracted increasing interest in the prevention of metabolic syndrome (MetS). Meanwhile, adiponectin has become a highly potential molecular target in the prevention of MetS. Our study will identify a potential vegan protein diet for the prevention of MetS using rat models. Thirty-six Wistar rats were randomly assigned into three groups and given diets containing one of the following proteins for 12 weeks: casein (CAS, control diet), soy protein (SOY), and gluten-soy mixed protein (GSM). Changes in metabolic parameters as well as the expressions of adiponectin and its receptors were identified. Compared to CAS diet, both SOY and GSM diets led to decreases in blood total cholesterol and triglycerides, but only GSM diet led to an increase in HDL-cholesterol; no marked difference was observed in blood glucose in all three groups; HOMA-IR was found lower only in SOY group. Among groups, the order of serum adiponectin level was found as GSM > SOY > CAS. Similar order pattern was also observed in expression of adiponectin in adipose tissue and AdipoR1 mRNA in skeletal muscle. Our results suggested for the first time that, besides SOY diet, GSM diet could also be a possible substitute of animal protein to prevent MetS.

  19. The Effect of Vegan Protein-Based Diets on Metabolic Parameters, Expressions of Adiponectin and Its Receptors in Wistar Rats

    PubMed Central

    Chen, Jie-Hua; Song, Jia; Chen, Yan; Ding, Qiang; Peng, Anfang; Mao, Limei

    2016-01-01

    Vegan protein-based diet has attracted increasing interest in the prevention of metabolic syndrome (MetS). Meanwhile, adiponectin has become a highly potential molecular target in the prevention of MetS. Our study will identify a potential vegan protein diet for the prevention of MetS using rat models. Thirty-six Wistar rats were randomly assigned into three groups and given diets containing one of the following proteins for 12 weeks: casein (CAS, control diet), soy protein (SOY), and gluten-soy mixed protein (GSM). Changes in metabolic parameters as well as the expressions of adiponectin and its receptors were identified. Compared to CAS diet, both SOY and GSM diets led to decreases in blood total cholesterol and triglycerides, but only GSM diet led to an increase in HDL-cholesterol; no marked difference was observed in blood glucose in all three groups; HOMA-IR was found lower only in SOY group. Among groups, the order of serum adiponectin level was found as GSM > SOY > CAS. Similar order pattern was also observed in expression of adiponectin in adipose tissue and AdipoR1 mRNA in skeletal muscle. Our results suggested for the first time that, besides SOY diet, GSM diet could also be a possible substitute of animal protein to prevent MetS. PMID:27763537

  20. A common variant in the CLDN7/ELP5 locus predicts adiponectin change with lifestyle intervention and improved fitness in obese individuals with diabetes

    PubMed Central

    Papandonatos, George D.; McCaffery, Jeanne M.; Peter, Inga; Pajewski, Nicholas M.; Erar, Bahar; Allred, Nicholette D.; Balasubramanyam, Ashok; Bowden, Donald W.; Brautbar, Ariel; Pi-Sunyer, F. Xavier; Ballantyne, Christie M.; Huggins, Gordon S.

    2015-01-01

    Overweight/obese individuals with Type 2 diabetes have low adiponectin levels, which may improve with lifestyle changes. We investigated whether genetic variants associated with adiponectin levels in genome-wide association studies (GWAS) would also be related with adiponectin changes in response to an intensive lifestyle intervention (ILI), potentially through mechanisms altering the adipose microenvironment via weight loss and/or improved cardiorespiratory fitness. Look AHEAD was a randomized trial comparing the cardiovascular benefits of ILI-induced weight loss and physical activity compared with diabetes support and education among overweight/obese individuals with Type 2 diabetes. In a subsample of Look AHEAD with adiponectin data and genetic consent (n = 1,351), we evaluated the effects of 24 genetic variants, demonstrated by GWAS to be cross-sectionally associated with adiponectin, on adiponectin change 1-yr postintervention. We explored via mediational analyses whether any differential effects by treatment arm were occurring through weight loss and/or improved fitness. A variant, rs222857, in the CLDN7 locus, potentially associated with epithelial barrier integrity and tight junction physiology, and a putative cis expression quantitative trail locus for elongator acetyltransferase complex subunit 5 (ELP5), predicted adiponectin increases within ILI (log-adiponectin in overall sample per copy: β ± SE = 0.05 ± 0.02, P = 0.008; in non-Hispanic whites: 0.06 ± 0.02, P = 0.009). The favorable effects of rs222857 (minor allele frequency 45.5%) appeared to be mediated by mechanisms associated with improved fitness, and not weight loss. This is the first study to identify a genetic variant that modifies adiponectin response to lifestyle intervention in overweight/obese diabetic individuals. PMID:25759378

  1. The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: A potential mechanism for the “obesity paradox”

    PubMed Central

    Ito, Ryuichi; Narita, Shintaro; Huang, Mingguo; Nara, Taketoshi; Numakura, Kazuyuki; Takayama, Koichiro; Tsuruta, Hiroshi; Maeno, Atsushi; Saito, Mitsuru; Inoue, Takamitsu; Tsuchiya, Norihiko; Satoh, Shigeru; Habuchi, Tomonori

    2017-01-01

    Although obesity increases the risk of renal cell carcinoma (RCC), obese patients with RCC experience longer survival than non-obese patients. However, the mechanism of this “obesity paradox” is unknown. We examined the impact of preoperative BMI, serum total adiponectin (sAd) level, total adiponectin secretion from perinephric adipose tissue, and intratumoral expression of adiponectin receptors on RCC aggressiveness and survival. We also investigated the mechanism underlying enhanced cancer aggressiveness in RCC cells stimulated with exogenous adiponectin. Overweight and obese patients had significantly lower grade cancers than normal patients in all patients and in those without metastasis (p = 0.003 and p = 0.027, respectively). Cancer-specific survival was significantly longer in overweight and obese patients than in normal patients in all patients (p = 0.035). There was a weak inverse correlation between sAd level and BMI in RCC patients (r = −0.344, p = 0.002). Tumor size was slightly correlated with sAd level, and high sAd was significantly associated with poor overall survival rates in patients with non-metastatic RCC (p = 0.035). Adiponectin levels in perinephric adipose tissue and intratumoral AdipoR1/R2 expression were not correlated with RCC aggressiveness or survival. Proliferation significantly increased in 786-O and Caki-2 cells exposed to exogenous adiponectin, whereas cell invasion and migration were unaffected. In addition, exogenous adiponectin significantly inhibited starvation- and metformin-induced apoptosis, and up-regulated p-AMPK and Bcl-xL levels. In summary, low BMI and high adiponectin levels are associated with aggressive cell behaviors and poor survival in surgically-treated RCC patients. The effects of adiponectin on proliferation and apoptosis might underlie the “obesity paradox” of RCC. PMID:28178338

  2. Plasma adiponectin in nonalcoholic fatty liver is related to hepatic insulin resistance and hepatic fat content, not to liver disease severity.

    PubMed

    Bugianesi, Elisabetta; Pagotto, Uberto; Manini, Rita; Vanni, Ester; Gastaldelli, Amalia; de Iasio, Rosaria; Gentilcore, Elena; Natale, Stefania; Cassader, Maurizio; Rizzetto, Mario; Pasquali, Renato; Marchesini, Giulio

    2005-06-01

    Plasma levels of adiponectin are decreased in patients with nonalcoholic fatty liver disease (NAFLD), but the relationship among plasma adiponectin, insulin sensitivity, and histological features is unclear. In 174 NAFLD patients and 42 controls, we examined plasma adiponectin concentrations in relation to 1) lipid profile, indices of insulin resistance, and features of the metabolic syndrome (n = 174); 2) hepatic insulin resistance (clamp technique with tracer infusion) (10 patients); and 3) histological features at liver biopsy (n = 116). When the data from all subjects were combined, plasma adiponectin levels were positively associated with increased age, female gender, and plasma high-density lipoprotein levels, and negatively associated with waist circumference, body mass index, triglycerides, indices of insulin resistance, and aminotransferase levels, and also predicted the presence of the metabolic syndrome. In step-wise regression, increased age, female gender, waist circumference, triglyceride levels, and homeostasis model assessment independently associated with adiponectin (adjusted R(2), 0.329). In NAFLD, adiponectin was only associated with increased age, female gender, and triglycerides (adjusted R(2), 0.245). When the measured histological parameters were included in the model, plasma adiponectin levels were also inversely proportional to the percentage of hepatic fat content (adjusted R(2), 0.221), whereas necroinflammation and fibrosis did not fit in the model. Adiponectin was negatively correlated with insulin-suppressed endogenous glucose production during the clamp (P = 0.011). The results demonstrate that decreased levels of circulating adiponectin in NAFLD are related to hepatic insulin sensitivity and to the amount of hepatic fat content. Hypoadiponectinemia in NAFLD is part of a metabolic disturbance characterized by ectopic fat accumulation in the central compartment.

  3. Methanolic leaf extract of Gymnema sylvestre augments glucose uptake and ameliorates insulin resistance by upregulating glucose transporter-4, peroxisome proliferator-activated receptor-gamma, adiponectin, and leptin levels in vitro

    PubMed Central

    Kumar, Puttanarasaiah Mahesh; Venkataranganna, Marikunte V.; Manjunath, Kirangadur; Viswanatha, Gollapalle L.; Ashok, Godavarthi

    2016-01-01

    Aims: The present study was undertaken to evaluate the effect of methanolic leaf extract of Gymnema sylvestre (MLGS) on glucose transport (GLUT) and insulin resistance in vitro. Materials and Methods: Peroxisome proliferator-activated receptor-gamma (PPAR-γ) and GLUT-4 expression were assessed in L6 myotubes for concluding the GLUT activity, and adiponectin and leptin expression was studied in 3T3 L1 murine adipocyte cell line to determine the effect of MLGS (250-750 μg/ml) on insulin resistance. Results: The findings of the experiments have demonstrated a significant and dose-dependent increase in glucose uptake in all the tested concentrations of MLGS, further the glucose uptake activity of MLGS (750 μg/ml) was at par with rosiglitazone (50 μg/ml). Concomitantly, MLGS has shown enhanced GLUT-4 and PPAR-γ gene expressions in L6 myotubes. Furthermore, cycloheximide (CHX) had completely abolished the glucose uptake activity of MLGS when co-incubated, which further confirmed that glucose uptake activity of MLGS was linked to enhanced expression of GLUT-4 and PPAR-γ. In addition, in another experimental set, MLGS showed enhanced expression of adiponectin and leptin, thus confirms the ameliorative effect of MLGS on insulin resistance. Conclusion: These findings suggest that MLGS has an enhanced glucose uptake activity in L6 myotubes, and ameliorate the insulin resistance in 3T3 L1 murine adipocyte cell line in vitro. PMID:27104035

  4. Fasting and postprandial regulation of the intracellular localization of adiponectin and of adipokines secretion by dietary fat in rats

    PubMed Central

    Olivares-García, V; Torre-Villalvazo, I; Velázquez-Villegas, L; Alemán, G; Lara, N; López-Romero, P; Torres, N; Tovar, A R; Díaz-Villaseñor, A

    2015-01-01

    Background/Objective: Dietary fat sources modulate fasting serum concentration of adipokines, particularly adiponectin. However, previous studies utilized obese animals in which adipose tissue function is severely altered. Thus, the present study aimed to assess the postprandial regulation of adipokine secretion in nonobese rats that consumed high-fat diet (HFD) composed of different types of fat for a short time. Methods: The rats were fed a control diet or a HFD containing coconut, safflower or soybean oil (rich in saturated fatty acid, monounsaturated fatty acid or polyunsaturated fatty acid, respectively) for 21 days. The serum concentrations of adiponectin, leptin, retinol, retinol-binding protein-4 (RBP-4), visfatin and resistin were determined at fasting and after refeeding. Adiponectin multimerization and intracellular localization, as well as the expression of endoplasmic reticulum (ER) chaperones and transcriptional regulators, were evaluated in epididymal white adipose tissue. Results: In HFD-fed rats, serum adiponectin was significantly decreased 30 min after refeeding. With coconut oil, all three multimeric forms were reduced; with safflower oil, only the high-molecular-weight (HMW) and medium-molecular-weight (MMW) forms were decreased; and with soybean oil, only the HMW form was diminished. These reductions were due not to modifications in mRNA abundance or adiponectin multimerization but rather to an increment in intracellular localization at the ER and plasma membrane. Thus, when rats consumed a HFD, the type of dietary fat differentially affected the abundance of endoplasmic reticulum resident protein 44 kDa (ERp44), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ (PPARγ) mRNAs, all of which are involved in the post-translational processing of adiponectin required for its secretion. Leptin, RBP-4, resistin and visfatin serum concentrations did not change during fasting, whereas modest alterations were observed after

  5. Adiponectin Provides Additional Information to Conventional Cardiovascular Risk Factors for Assessing the Risk of Atherosclerosis in Both Genders

    PubMed Central

    Yoon, Jin-Ha; Kim, Sung-Kyung; Choi, Ho-June; Choi, Soo-In; Cha, So-Youn; Koh, Sang-Baek

    2013-01-01

    Background This study evaluated the relation between adiponectin and atherosclerosis in both genders, and investigated whether adiponectin provides useful additional information for assessing the risk of atherosclerosis. Methods We measured serum adiponectin levels and other cardiovascular risk factors in 1033 subjects (454 men, 579 women) from the Korean Genomic Rural Cohort study. Carotid intima–media-thickness (CIMT) was used as measure of atherosclerosis. Odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated using multiple logistic regression, and receiver operating characteristic curves (ROC), the category-free net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. Results After adjustment for conventional cardiovascular risk factors, such as age, waist circumference, smoking history, low-density and high-density lipoprotein cholesterol, triglycerides, systolic blood pressure and insulin resistance, the ORs (95%CI) of the third tertile adiponectin group were 0.42 (0.25–0.72) in men and 0.47 (0.29–0.75) in women. The area under the curve (AUC) on the ROC analysis increased significantly by 0.025 in men and 0.022 in women when adiponectin was added to the logistic model of conventional cardiovascular risk factors (AUC in men: 0.655 to 0.680, p = 0.038; AUC in women: 0.654 to 0.676, p = 0.041). The NRI was 0.32 (95%CI: 0.13–0.50, p<0.001), and the IDI was 0.03 (95%CI: 0.01–0.04, p<0.001) for men. For women, the category-free NRI was 0.18 (95%CI: 0.02–0.34, p = 0.031) and the IDI was 0.003 (95%CI: −0.002–0.008, p = 0.189). Conclusion Adiponectin and atherosclerosis were significantly related in both genders, and these relationships were independent of conventional cardiovascular risk factors. Furthermore, adiponectin provided additional information to conventional cardiovascular risk factors regarding the risk of atherosclerosis. PMID:24116054

  6. Circulating levels of adiponectin, resistin, and visfatin after mud-bath therapy in patients with bilateral knee osteoarthritis

    NASA Astrophysics Data System (ADS)

    Fioravanti, Antonella; Giannitti, Chiara; Cheleschi, Sara; Simpatico, Antonella; Pascarelli, Nicola Antonio; Galeazzi, Mauro

    2015-11-01

    Adipocytokines, including adiponectin, resistin, and visfatin may play an important role in the pathophysiology of osteoarthritis (OA). Spa therapy is one of the most commonly used non-pharmacological approaches for OA, but its mechanisms of action are not completely known. The aim of the present study was to assess whether a cycle of mud-bath therapy (MBT) influences the serum levels of adiponectin, resistin, and visfatin in patients with knee OA. As part of a prospective randomized, single blind-controlled trial evaluating the efficacy of MBT in knee OA, we included in this study 95 outpatients. One group ( n = 49) received a cycle of MBT at the spa center of Chianciano Terme (Italy) in addition to the usual treatment, and one group (control group; n = 46) continued their regular care routine alone. Patients were assessed at basal time and at the end of the study (15 days) for clinical and biochemical parameters. Clinical assessments included spontaneous pain on a visual analog scale (VAS) score and the Western Ontario and McMaster Universities index (WOMAC) subscores for knee OA evaluated as total pain score (W-TPS), total stiffness score (W-TSS), and total physical function score (W-TPFS). Adiponectin, resistin and visfatin serum levels were assessed by enzyme immunoassay methods. At the end of the mud-bath therapy, serum adiponectin levels showed a significant decrease ( p < 0.001), while no significant modifications were found in the control group at day 15. Serum resistin showed a significant decrease ( p < 0.0001) in the MBT group at the end of the study and a significant increase in the control patients ( p < 0.001). No significant modifications of visfatin were found in MBT. Furthermore, we tested the relationships between demographic and clinical parameters and adipocytokine concentrations measured in the MBT group at basal and at the end of the study. In conclusion, the present study shows that a cycle of MBT can modify serum levels of adiponectin and

  7. Associations of Adiponectin and Leptin with Incident Coronary Heart Disease and Ischemic Stroke in African Americans: The Jackson Heart Study

    PubMed Central

    Bidulescu, Aurelian; Liu, Jiankang; Chen, Zhimin; Hickson, DeMarc A.; Musani, Solomon K.; Samdarshi, Tandaw E.; Fox, Ervin R.; Taylor, Herman A.; Gibbons, Gary H.

    2013-01-01

    Background: Because the predictive significance of previously reported racial differences in leptin and adiponectin levels remains unclear, we assessed the prospective association of these adipokines with the risk of cardiovascular disease (CVD) events in African Americans, a population with a high prevalence of cardiometabolic risk factors. Methods: Serum specimens from 4,571 Jackson Heart Study participants without prevalent CVD at baseline examination (2000–2004) were analyzed for adiponectin and leptin levels. Cox proportional hazard regression models were used to estimate the associations of the two adipokines with incident coronary heart disease (CHD) and incident ischemic stroke. Results: During 6.2 years average of follow-up, 98 incident CHD and 87 incident ischemic stroke events were documented. Among study participants (64% women; mean age 54 ± 13 years), the mean (standard deviation, SD) was 6.04 (4.32) μg/mL in women and 4.03 (3.14) μg/mL in men for adiponectin and 37.35 (23.90) ng/mL in women and 11.03 (10.05) ng/mL in men for leptin. After multivariable adjustment that included age, body mass index, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, insulin resistance by homeostasis model assessment for insulin resistance, systolic blood pressure, hypertension medication, smoking, and physical activity, adiponectin was directly associated in women with incident stroke, HR = 1.41 (1.04–1.91) per one SD increase (p = 0.03), but not in men (p = 0.42). It was not associated with incident CHD in women or men. Leptin was not associated with incident CHD or incident stroke. Conclusion: In the largest community-based African American cohort, adiponectin was associated among women with a higher risk of incident stroke. Whether adiponectin harbors harmful properties, or it is produced in response to vascular inflammation to counter the atherosclerotic process, or the putative “adiponectin resistance

  8. Different forms of adiponectin reduce the apoptotic and damaging effect of cigarette smoke extract on human bronchial epithelial cells

    PubMed Central

    Cheng, Meng-Yu; Liu, Hu; Zhang, Tie-Mei; Xu, Jian-Ying

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is a common respiratory disease, in which adiponectin may serve an important role. The present study investigated the role of adiponectin in the apoptotic and damaging effect of cigarette smoke extract (CSE) on human bronchial epithelial cells (16HBECs). An MTT assay showed that CSE significantly inhibited the proliferation of 16HBECs (F=1808.88, P<0.01). The 16HBECs were treated with different concentrations of high molecular weight (HMW) adiponectin and globular domain (gAd) adiponectin and it was observed that HMW and gAd dose-dependently inhibited the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-8, and the generation of 4-hydroxy-nonenal and reactive oxygen species (ROS) in 16HBECs, thereby blocking the upregulating effect of CSE on these factors. However, the inhibitory effect of gAd on TNF-α and IL-8 expression was stronger compared with that of HMW, but the suppressing effect of HMW on ROS production was superior compared with that of gAd. Further testing of apoptosis indicated that CSE and HMW promoted the apoptosis of 16HBECs. However, such effects of HMW declined with an increase in concentration. In contrast, gAd showed an inhibitory effect on apoptosis and inhibited the occurrence of CSE-induced apoptosis in a dose-dependent manner. Therefore, the present study demonstrated that different forms of adiponectin may have different mechanisms of action, suggesting that further exploration of their effects may open a new avenue for the treatment of COPD. PMID:28105143

  9. No effect of modest selenium supplementation on insulin resistance in UK pregnant women, as assessed by plasma adiponectin concentration.

    PubMed

    Mao, Jinyuan; Bath, Sarah C; Vanderlelie, Jessica J; Perkins, Anthony V; Redman, Christopher W G; Rayman, Margaret P

    2016-01-14

    Concern has been expressed recently that Se may increase the risk of type 2 diabetes, but this has not been tested in a randomised-controlled trial (RCT) in pregnant women. We took advantage of having stored plasma samples from the Se in Pregnancy Intervention (SPRINT) RCT of Se supplementation in pregnancy to test the effect of Se supplementation on a marker of insulin resistance in UK pregnant women. Because our blood samples were not fasted, we measured plasma adiponectin concentration, a recognised marker of insulin resistance that gives valid measurements in non-fasted samples, as diurnal variability is minor and there is no noticeable effect of food intake. In SPRINT, 230 primiparous UK women were randomised to treatment with Se (60 μg/d) or placebo from 12 weeks of gestation until delivery. We hypothesised that supplementation with Se at a nutritional level would not exacerbate the fall in adiponectin concentration that occurs in normal pregnancy, indicating the lack of an adverse effect on insulin resistance. Indeed, there was no significant difference between the two groups in the change in adiponectin from 12 to 35 weeks (P=0·938), nor when the analysis was restricted to the bottom or top quartiles of baseline whole-blood Se (P=0·515 and 0·858, respectively). Cross-sectionally, adiponectin concentration was not associated with any parameter of Se status, either at 12 or 35 weeks. It is reassuring that a nutritional dose of Se had no adverse effect on the concentration of adiponectin, a biomarker of insulin resistance, in pregnant women of modest Se status.

  10. Role of adiponectin in the metabolic effects of cannabinoid type 1 receptor blockade in mice with diet-induced obesity

    PubMed Central

    Godlewski, Grzegorz; Earley, Brian J.; Zhou, Liang; Jourdan, Tony; Szanda, Gergö; Cinar, Resat; Kunos, George

    2013-01-01

    The adipocyte-derived hormone adiponectin promotes fatty acid oxidation and improves insulin sensitivity and thus plays a key role in the regulation of lipid and glucose metabolism and energy homeostasis. Chronic cannabinoid type 1 (CB1) receptor blockade also increases lipid oxidation and improves insulin sensitivity in obese individuals or animals, resulting in reduced cardiometabolic risk. Chronic CB1 blockade reverses the obesity-related decline in serum adiponectin levels, which has been proposed to account for the metabolic effects of CB1 antagonists. Here, we investigated the metabolic actions of the CB1 inverse agonist rimonabant in high-fat diet (HFD)-induced obese adiponectin knockout (Adipo−/−) mice and their wild-type littermate controls (Adipo+/+). HFD-induced obesity and its hormonal/metabolic consequences were indistinguishable in the two strains. Daily treatment of obese mice with rimonabant for 7 days resulted in significant and comparable reductions in body weight, serum leptin, free fatty acid, cholesterol, and triglyceride levels in the two strains. Rimonabant treatment improved glucose homeostasis and insulin sensitivity to the same extent in Adipo+/+ and Adipo−/− mice, whereas it reversed the HFD-induced hepatic steatosis, fibrosis, and hepatocellular damage only in the former. The adiponectin-dependent, antisteatotic effect of rimonabant was mediated by reduced uptake and increased β-oxidation of fatty acids in the liver. We conclude that reversal of the HFD-induced hepatic steatosis and fibrosis by chronic CB1 blockade, but not the parallel reduction in adiposity and improved glycemic control, is mediated by adiponectin. PMID:24381003

  11. Increased plasma isoprostane is associated with visceral fat, high molecular weight adiponectin, and metabolic complications in obese children.

    PubMed

    Araki, Shunsuke; Dobashi, Kazushige; Yamamoto, Yukiyo; Asayama, Kohtaro; Kusuhara, Koichi

    2010-08-01

    Oxidative stress is considered to be increased in obese subjects. However, the association of oxidative stress with visceral adiposity and adiponectin level is not fully understood in children. Forty-four obese Japanese children and adolescents, 28 boys and 16 girls, with median age of 9.9 years [5.2-13.8 years], and the 28 age-matched non-obese healthy controls, 15 boys and 13 girls, were enrolled in this study. The median BMI Z scores were +2.21 [1.31-4.38] for the obese subjects and -0.72 [-2.11-1.31] for the control. Plasma concentrations of 8-epi-prostaglandin F₂α (isoprostane), a marker of oxidative stress, and adiponectin fractions were assayed using ELISA. 8-epi-PGF₂α levels were significantly higher in the obese group (37.1 [4.7-112.7], median and the range) than in the control (11.5 [4.5-27.3]). In a univariate analysis, concentrations of 8-epi-PGF₂α positively correlated with visceral adipose tissue area measured by computed tomography, waist circumference, serum triglycerides, alanine aminotransferase, insulin levels, and the homeostasis of minimal assessment of insulin resistance and inversely correlated with high-density-lipoprotein cholesterol and high-molecular weight (HMW) adiponectin. Total-, medium-, or low-molecular weight adiponectin fraction did not show a significant correlation with 8-epi-PGF₂α Forty of 44 obese children had one or more metabolic complications. The 8-epi-PGF[Formula: see text] levels also elevated with increasing numbers of obesity-related complications. These results suggest that oxidative stress is enhanced in relation to visceral fat accumulation and decreasing HMW adiponectin level in childhood obesity. Oxidative stress may be associated with the development of obesity-related complications.

  12. An acute intake of a walnut-enriched meal improves postprandial adiponectin response in healthy young adults.

    PubMed

    Lozano, Aquiles; Perez-Martinez, Pablo; Marin, Carmen; Tinahones, Francisco J; Delgado-Lista, Javier; Cruz-Teno, Cristina; Gomez-Luna, Purificacion; Rodriguez-Cantalejo, Fernando; Perez-Jimenez, Francisco; Lopez-Miranda, Jose

    2013-12-01

    A deficit in adiponectin plays an important causal role in insulin resistance and metabolic syndrome. We hypothesized that as seen during the fasting state, the intake of a walnut-enriched meal increased postprandial adiponectin. Twenty-one healthy white men followed a 4-week baseline diet and then consumed 3 fat-loaded meals that included 1 g fat/kg body weight (65% fat) according to a randomized crossover design: olive oil-enriched meal (22% saturated fatty acids [SFA], 38% monounsaturated fatty acids [MUFA], 4% polyunsaturated fatty acids [PUFA]), butter-enriched meal (35% SFA, 22% MUFA, 4% PUFA), and walnut-enriched meal (20% SFA, 24% MUFA, 16% PUFA, and 4% α-linolenic acid). Leptin, resistin, adiponectin, and free fatty acids were determined at 0, 3, 6, and 8.5 hours after the fat load. After the walnut-enriched meal, plasma adiponectin concentrations were higher at 3 and 6 hours (P = .011, P = .046, respectively) compared with the butter-enriched meal and higher at 6 hours compared with the olive oil-enriched meal (P = .036). Free fatty acid levels decreased from baseline at 3 hours after the walnut-enriched meal (P = .001). No differences were observed between the 3 meals for leptin and resistin responses. Our data confirmed a beneficial profile in the postprandial response to walnuts, source of omega-3 PUFA with an increased postprandial adiponectin and lower postprandial free fatty acid responses. These findings suggest that the postprandial state is important for understanding the possible cardioprotective effects associated with omega-3 PUFA dietary fat.

  13. Smoking Habits and Neuropeptides: Adiponectin, Brain-derived Neurotrophic Factor, and Leptin Levels

    PubMed Central

    Won, Yong Lim; Ko, Kyung Sun; Roh, Ji won

    2014-01-01

    This study aimed to identify changes in the level of neuropeptides among current smokers, former smokers, and individuals who had never smoked, and how smoking habits affect obesity and metabolic syndrome (MetS). Neuropeptide levels, anthropometric parameters, and metabolic syndrome diagnostic indices were determined among male workers; 117 of these had never smoked, whereas 58 and 198 were former and current smokers, respectively. The total sample comprised 373 male workers. The results obtained from anthropometric measurements showed that current smokers attained significantly lower body weight, body mass index, waist circumference, and abdominal fat thickness values than former smokers and those who had never smoked. Current smokers’ eating habits proved worse than those of non-smokers and individuals who had never smoked. The level of brain-derived neurotrophic factor (BDNF) in the neuropeptides in the case of former smokers was 23.6 ± 9.2 pg/ml, higher than that of current smokers (20.4 ± 6.1) and individuals who had never smoked (22.4 ± 5.8) (F = 6.520, p = 0.002). The level of adiponectin among former smokers was somewhat lower than that of current smokers, whereas leptin levels were higher among former smokers than current smokers; these results were not statistically significant. A relationship was found between adiponectin and triglyceride among non-smokers (odds ratio = 0.660, β value = −0.416, p < 0.01) and smokers (odds ratio = 0.827, β value = −0.190, p < 0.05). Further, waist circumference among non-smokers (odds ratio = 1.622, β value = 0.483, p < 0.001) and smokers (odds ratio = 1.895, β value = 0.639, p < 0.001) was associated with leptin. It was concluded that cigarette smoking leads to an imbalance of energy expenditure and appetite by changing the concentration of neuropeptides such as adiponectin, BDNF, leptin, and hsCRP, and influences food intake, body weight, the body mass index, blood pressure, and abdominal fat, which are

  14. Experimental Hyperthyroidism Decreases Gene Expression and Serum Levels of Adipokines in Obesity

    PubMed Central

    Luvizotto, Renata de Azevedo Melo; do Nascimento, André Ferreira; de Síbio, Maria Teresa; Olímpio, Regiane Marques Castro; Conde, Sandro José; Lima-Leopoldo, Ana Paula; Leopoldo, André Soares; Cicogna, Antonio Carlos; Nogueira, Célia Regina

    2012-01-01

    Aims. To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. Main Methods. Male Wistar rats were randomly divided into two groups: control (C)—fed with commercial chow ad libitum—and obese (OB)—fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25 μg triiodothyronine (T3)/100 BW (OT). The T3 dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. Results. T3 treatment was effective, increasing fT3 levels and decreasing fT4 and TSH serum concentration. Administration of T3 promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. Conclusions. Our results suggest that T3 modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T3 and adipokines in obesity. PMID:22645452

  15. LOW 24-HOUR ADIPONECTIN AND HIGH NOCTURNAL LEPTIN CONCENTRATIONS IN A CASE CONTROL STUDY OF COMMUNITY-DWELLING PREMENOPAUSAL WOMEN WITH MAJOR DEPRESSION The P.O.W.E.R. Study

    PubMed Central

    Cizza, Giovanni; Nguyen, Vi T.; Eskandari, Farideh; Duan, Zhigang; Wright, Elizabeth C.; Reynolds, James C.; Ahima, Rexford S.; Blackman, Marc R.

    2012-01-01

    Objective Major depressive disorder (MDD) is associated with immune system dysfunction and disruption of multiple circadian systems. Adiponectin is an adipocytokine with anti-inflammatory and anti-atherogenic effects. Circulating concentrations are inversely related to adiposity and risks of metabolic syndrome and diabetes mellitus. Our goals were to: A) establish whether premenopausal women with MDD exhibit decreased plasma adiponectin concentrations and/or disruption of circadian adiponectin rhythmicity; B) assess whether there is a relationship between adiponectin and MDD; C) explore the temporal relationships among adiponectin, leptin, ACTH and cortisol secretion. Method Case-control study of community-dwelling premenopausal women with MDD and age- and BMI-matched-control subjects (N=23/group). Main outcome measures were circulating concentrations of adiponectin, leptin, ACTH, and cortisol measured hourly for 24h. Results Women with MDD had approximately 30% lower mean 24h concentrations of adiponectin than did control subjects. Adiponectin was inversely related to depression severity and total duration of disease, suggesting a causal link. In contrast, nocturnal leptin concentrations were higher in the MDD versus control groups. Leptin was inversely related to cortisol and adiponectin both in subjects with depression and in control subjects. In cross-correlation analyses, the relationship between ACTH and cortisol was stronger in women with MDD than in control subjects, consistent with HPA-axis activation in MDD. Conclusions Reduced daily adiponectin production may increase the risk of diabetes mellitus, and elevated leptin may contribute to osteoporosis, in premenopausal women with MDD. PMID:20492842

  16. Globular Adiponectin Causes Tolerance to LPS-Induced TNF-α Expression via Autophagy Induction in RAW 264.7 Macrophages: Involvement of SIRT1/FoxO3A Axis.

    PubMed

    Pun, Nirmala Tilija; Subedi, Amit; Kim, Mi Jin; Park, Pil-Hoon

    2015-01-01

    Adiponectin, an adipokine predominantly produced from adipose tissue, exhibited potent anti-inflammatory properties. In particular, it inhibits production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In the present study, we investigated the role of autophagy induction in the suppression of Lipopolysaccharide (LPS) -induced TNF-α expression by globular adiponectin (gAcrp) and its potential mechanisms. Herein, we found that gAcrp treatment increased expression of genes related with autophagy, including Atg5 and microtubule-associated protein light chain (LC3B), induced autophagosome formation and autophagy flux in RAW 264.7 macrophages. Similar results were observed in primary macrophages isolated peritoneum of mice. Interestingly, inhibition of autophagy by pretreatment with Bafilomycin A1 or knocking down of LC3B gene restored suppression of TNF-α expression, tumor necrosis factor receptor- associated factor 6 (TRAF6) expression and p38MAPK phosphorylation by gAcrp, implying a critical role of autophagy induction in the development of tolerance to LPS-induced TNF-α expression by gAcrp. We also found that knocking-down of FoxO3A, a forkhead box O member of transcription factor, blocked gAcrp-induced expression of LC3II and Atg5. Moreover, gene silencing of Silent information regulator 1 (SIRT1) blocked both gAcrp-induced nuclear translocation of FoxO3A and LC3II expression. Finally, pretreatment with ROS inhibitors, prevented gAcrp-induced SIRT1 expression and further generated inhibitory effects on gAcrp-induced autophagy, indicating a role of ROS production in gAcrp-induced SIRT1 expression and subsequent autophagy induction. Taken together, these findings indicate that globular adiponectin suppresses LPS-induced TNF-α expression, at least in part, via autophagy activation. Furthermore, SIRT1-FoxO3A

  17. Genes

    MedlinePlus

    ... Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Genes URL of this page: //medlineplus.gov/ency/article/ ...

  18. Manganese supplementation increases adiponectin and lowers ICAM-1 and creatinine blood levels in Zucker type 2 diabetic rats, and downregulates ICAM-1 by upregulating adiponectin multimerization protein (DsbA-L) in endothelial cells.

    PubMed

    Burlet, Elodie; Jain, Sushil K

    2017-01-13

    Blood and tissue levels of manganese (Mn) are lower in type 2 diabetic and atherosclerosis patients compared with healthy subjects. Adiponectin has anti-diabetic and anti-atherogenic properties. Impairment in Disulfide bond A-like protein (DsbA-L) is associated with low adiponectin levels and diabetes. This study investigates the hypothesis that the beneficial effects of Mn supplementation are mediated by adiponectin and DsbA-L. At 6 weeks of age, Male Zucker diabetic fatty rats (ZDF) were randomly divided into two groups: diabetic controls and Mn-supplemented diabetic rats. Each rat was supplemented with Mn (D+Mn, 16 mg/kg BW) or water (placebo, D+P) daily for 7 weeks by oral gavage. For cell culture studies, Human Umbilical Vein Endothelial Cells (HUVEC) or 3T3L1 adipocytes were pretreated with Mn (0-10 µM MnCl2) for 24 h, followed by high glucose (HG, 25 mM) or normal glucose (5 mM) exposure for another 24 h. Mn supplementation resulted in higher adiponectin (p = 0.01), and lower ICAM-1 (p = 0.04) and lower creatinine (p = 0.04) blood levels compared to those in control ZDF rats. Mn-supplemented rats also caused reduced oxidative stress (ROS) and NADPH oxidase, and higher DsbA-L expression in the liver (p = 0.03) of ZDF rats compared to those in livers of control rats; however, Fe levels in liver were lower but not significant (p = 0.08). Similarly, treatment with high glucose (25 mM) caused a decrease in DsbA-L, which was prevented by Mn supplementation in HUVEC and adipocytes. Mechanistic studies with DsbA-L siRNA showed that the beneficial effects of Mn supplementation on ROS, NOX4, and ICAM-1 expression were abolished in DsbA-L knock-down HUVEC. These studies demonstrate that DsbA-L-linked adiponectin mediates the beneficial effects observed with Mn supplementation and provides evidence for a novel mechanism by which Mn supplementation can increase adiponectin and reduce the biomarkers of endothelial dysfunction in diabetes.

  19. Role of adiponectin and some other factors linking type 2 diabetes mellitus and obesity

    PubMed Central

    Chakraborti, Chandra Kanti

    2015-01-01

    Because of the intimate association of obesity with type 2 diabetes mellitus (T2DM), during the last two decades, extensive research work is being conducted to find out whether the coexistence of the two is a simple association or there is a positive correlating link between the two. In this article, an attempt has been made to collect and analyse the recent developments in this field and to arrive at a conclusion on the subject. The possible role of several important factors (obtained from adipocytes/not of adipocyte origin) in linking the two has been discussed in detail. Some of the agents, specifically adiponectin, are beneficial (i.e., reduce the incidence of both), while others are harmful (i.e., increase their incidence). From the analysis, it appears that obesity and T2DM are intimately linked. PMID:26557957

  20. Reduced circulating oxytocin and High-Molecular-Weight adiponectin are risk factors for metabolic syndrome.

    PubMed

    Yuan, Guoyue; Qian, Weiyun; Pan, Ruirong; Jia, Jue; Jiang, Dan; Yang, Qichao; Wang, Su; Liu, Yuanxin; Yu, Shuqin; Hu, Hao; Sun, Wenjun; Ye, Jingjing; Mao, Chaoming; Zhuang, Ruo; Zhou, Libin

    2016-07-30

    The neurohypophysial hormone, oxytocin, is involved in the regulation of energy metabolism. Adiponectin (APN) is an adipose tissue-specific serum protein that inversely associates with metabolic syndrome (MetS). High-molecular-weight adiponectin (HMW APN) is considered the active form. In the present study, we aimed to determine the relationships of oxytocin and HMW APN to MetS and investigate whether or not the combination of oxytocin and HMW APN is associated with further metabolic abnormalities compared to each of them alone. A total of 170 subjects (75 with MetS and 95 non-MetS) were enrolled. Anthropometric parameters, oral glucose tolerance test (OGTT), blood lipids, hs-CRP, oxytocin and HMW APN levels were measured. Compared with non-MetS subjects, serum oxytocin and HMW APN levels were significantly lower in subjects with MetS (P<0.01). We then classified the subjects into three groups: high oxytocin and high HMW APN levels (high score group), low oxytocin and low HMW APN levels (low score group) and others. Participants in low score group showed the worst metabolic profiles and were more likely to have MetS compared to the other two group. In Spearman rank correlation coefficient, the classification by the combination of oxytocin and HMW APN was significantly correlated with a larger number of metabolic risk factors compared with classification by each of them alone. Individuals with low circulating oxytocin levels coupled with low HMW APN levels were at significantly increased risk of MetS. The combination of both markers would be useful for identifying MetS high risk patients.

  1. Adiponectin Inhibits LPS-Induced HMGB1 Release through an AMP Kinase and Heme Oxygenase-1-Dependent Pathway in RAW 264 Macrophage Cells

    PubMed Central

    Kaede, Ryuji; Okamatsu-Ogura, Yuko

    2016-01-01

    High mobility group protein B1 (HMGB1) is a late inflammatory media