Disease relevance of ADIPOQ

• CONCLUSIONS: Previous findings that the ADIPOQ 45T-->G variant contributes to overall fatness and abdominal obesity are confirmed [1].
• RESULTS: The patients' fat showed higher values of apoptosis (P=0.005), fibrosis (P<0.05), vessel density (P=0.001) and macrophage infiltration (P<0.05) than the controls' fat, together with lower adiponectin and leptin mRNA levels and higher interleukin (IL)-6 and tumour necrosis factor (TNF)alpha mRNA levels [2].
• Serum adiponectin, an adipokine with anti-inflammatory and insulin-sensitising properties, has been shown to be lower in patients with gestational diabetes mellitus, a state of greater insulin resistance than normal pregnancies [3].
• Hypoadiponectinaemia and high risk of type 2 diabetes are associated with adiponectin-encoding (ACDC) gene promoter variants in morbid obesity: evidence for a role of ACDC in diabesity [4].
• Adiponectin, inflammation, and the expression of the metabolic syndrome in obese individuals: the impact of rapid weight loss through caloric restriction [5].

Psychiatry related information on ADIPOQ

• Serum adiponectin and resistin concentrations in patients with restrictive and binge/purge form of anorexia nervosa and bulimia nervosa [6].
• We therefore aimed to investigate the distribution of adiponectin oligomers in human serum in relation to physical activity [7].
• After adjustment for age, BMI, smoking, alcohol consumption, duration of diabetes, and other lifestyle factors, adiponectin was associated with a decreased risk for CHD events [8].
• These findings suggest that abnormal feeding behavior in the patients with eating disorders may reduce circulating adiponectin level, and weight recovery can restore it [9].
• In conclusion, circulating concentrations of leptin, adiponectin and resistin are markedly altered in patients with chronic heroin addiction [10].

High impact information on ADIPOQ

• Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes [11].
• Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30) is a hormone secreted by adipocytes that acts as an antidiabetic and anti-atherogenic adipokine [11].
• Cloning of adiponectin receptors that mediate antidiabetic metabolic effects [11].
• We showed that AdipoR1 and AdipoR2 serve as receptors for globular and full-length adiponectin and mediate increased AMP-activated protein kinase, peroxisome proliferator-activated receptor-alpha ligand activities, and glucose uptake and fatty-acid oxidation by adiponectin [12].
• In fact, obesity-linked down-regulation of adiponectin was a mechanism whereby obesity could cause insulin resistance and diabetes [12].

Chemical compound and disease context of ADIPOQ

• After 4-6 wk of weight loss, there was marked improvement in glucose, insulin, leptin, and triglycerides, whereas adiponectin and TNF-alpha concentrations did not change [5].
• Plasma log-adiponectin levels correlated negatively with diabetes mellitus (DM), body mass index (BMI), log-PAI-1 (r=-0.284, p<0.001), triglyceride (TG), and remnant-like particles cholesterol (RLP-C), and positively with high-density lipoprotein cholesterol (HDL-C) levels [13].
• A case-controlled study was designed to measure plasma adiponectin levels and investigate the effects of rosiglitazone on adiponectin levels in type 2 diabetic patients with proteinuria [14].
• The inverse association between adiponectin and CHD was consistent across strata of aspirin use, family history of myocardial infarction, alcohol consumption, insulin use, duration of diabetes, and levels of HbA(1c), triglycerides, C-reactive protein, and HDL cholesterol [8].
• To determine the role of genetic variation in ACDC in susceptibility to obesity and type 2 diabetes in Pima Indians, we screened the promoter, exons, and exon-intron boundaries of the gene to identify allelic variants [15].

Biological context of ADIPOQ

• AIMS/HYPOTHESIS: The aim of this study was to examine whether genetic variation in ADIPOQ, ADIPOR1 and ADIPOR2 may contribute to increased susceptibility to components of the insulin resistance syndrome (IRS) [16].
• RESULTS: Of the eight SNPs examined in the ADIPOQ gene, rs4632532 and rs182052 exhibited significant associations with BMI (p=0.029 and p=0.032), fasting specific insulin (p=0.023 and p=0.026), sum of skin folds (SS) (p=0.0089 and p=0.0084) and homeostasis model assessment of insulin sensitivity (HOMA-%S) (p=0.015 and p=0.016) [16].
• MATERIALS AND METHODS: We genotyped single-nucleotide polymorphisms (SNPs) in ADIPOQ, ADIPOR1 and ADIPOR2 in Mexican American subjects (N=439) and performed an association analysis of IRS-related traits [16].
• CONCLUSIONS/INTERPRETATION: These results provide evidence for association of SNPs in ADIPOQ and its receptors with multiple IRS-related phenotypes [16].
• Subjects carrying the minor ADIPOQ allele (G allele) who were rare homozygotes (C/C) for the ADIPOR1 SNP had a higher RQ (P = 0.003) and greater overall (P < 0.03) and abdominal (P < 0.05) adiposity than did persons with other genotype combinations [1].

Anatomical context of ADIPOQ

• Recently, we have cloned adiponectin receptors in the skeletal muscle (AdipoR1) and liver (AdipoR2), which appear to comprise a novel cell-surface receptor family [12].
• Obesity decreased expression levels of AdipoR1/R2, thereby reducing adiponectin sensitivity, which finally leads to insulin resistance, the so-called "vicious cycle." Most recently, we showed that osmotin, which is a ligand for the yeast homolog of AdipoR (PHO36), activated AMPK via AdipoR in C2C12 myocytes [12].
• Adiponectin is exclusively secreted by adipose tissue and is abundantly present in the circulation, with important effects on metabolism [17].
• When men and women with a BMI <30 kg/m(2) were compared, women had a twofold higher percent body fat, yet their plasma adiponectin levels were 65% higher (8.6 +/- 1.1 and 14.2 +/- 1.6 micro g/ml in men and women, respectively; P < 0.02) [18].
• Bovine aortic endothelial cells in primary culture loaded with the NO-specific fluorescent dye 4,5-diaminofluorescein diacetate (DAF-2 DA) were treated with lysophosphatidic acid (LPA) (a calcium-releasing agonist) or adiponectin (10 microg/ml bacterially produced full-length adiponectin) [19].

Associations of ADIPOQ with chemical compounds

• Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice [11].
• Conversely, adiponectin and leptin were directly and inversely correlated, respectively, with VLDL apoB catabolism and HDL cholesterol concentration (P < 0.05) [20].
• In univariate regression, plasma adiponectin and leptin concentrations were inversely and directly associated, respectively, with plasma triglyceride; HOMA score; and visceral, subcutaneous, and total ATMs [20].
• Our aim was to study the effects of troglitazone on adiponectin levels in lean, obese, and diabetic subjects [21].
• Our findings show that TZD treatment increased adiponectin levels in all subjects, including normal subjects in which no other effects of TZDs are observed [21].

Physical interactions of ADIPOQ

• Adiponectin specifically bound to HAECs in a saturable manner and inhibited TNF-alpha-induced mRNA expression of monocyte adhesion molecules without affecting the interaction between TNF-alpha and its receptors [22].
• APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function [23].
• Absence of BBB permeation by obestatin and adiponectin was in contrast to the saturable transport of human ghrelin reported previously [24].
• Both types of adiponectin bound to biglycan in a dose-dependent manner [25].
• Notably, a peptide fragment (DQETTTQGPGVLLPLPKGACTGWMA) corresponding to amino acid residues 17-41 of human adiponectin could bind to restricted types of cells and block adiponectin-induced cyclooxygenase-2 gene expression and prostaglandin E(2) production in MS-5 stromal cells [26].

Regulatory relationships of ADIPOQ

• Suppression of AdipoR1 with siRNA abolished the adiponectin-regulated RANKL and OPG mRNA expression in osteoblasts [27].
• Finally, TNF-alpha was found in vitro to inhibit human AT adiponectin mRNA by 80% (P < 0.05) [28].
• Adiponectin suppressed both the phagocytosis of apoptotic cells and the IL-8 production [29].
• Furthermore, both f- and g-adiponectin drastically suppress constitutive STAT3 activation in DU145 and HepG2 cells [30].
• Furthermore, the gastric signal peptide ghrelin is known to suppress adiponectin expression in adipocyte cell culture models [31].

Other interactions of ADIPOQ

• We studied five lean and five obese young men [ages: 24.2 +/- 1.0 (lean) and 21.8 +/- 1.6 (obese) years (difference not significant); body mass indexes: 35.0 +/- 1.3 and 23.0 +/- 0.3 kg/m2 (P = 0.01)], sampled blood every 7 min over 24 h, and measured ghrelin, adiponectin, and leptin in 2,070 samples for a total of 6,210 data points [17].
• Adiponectin has antilipogenic and anti-inflammatory effects, while tumor necrosis factor alpha (TNF-alpha) reduces insulin sensitivity and has proinflammatory effects [32].
• Plasma tumor necrosis factor-alpha, resistin, macrophage chemoattractant protein-1, and adiponectin concentrations were similar in the portal vein and radial artery in obese subjects [33].
• ADIPOR1 is widely expressed in tissues, including muscle, liver, and pancreas, and binds the globular form of adiponectin with high affinity [34].
• Dose-response studies with J774-MacCM revealed that 80 and 100% of J774-MacCM completely suppressed triacylglycerol accumulation as well as the induction of fatty acid synthase, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, and adiponectin [35].

Analytical, diagnostic and therapeutic context of ADIPOQ

• Baseline adiponectin levels were significantly lower in the diabetic than the lean subjects (9.0 +/- 1.7 vs. 16.7 +/- 2.7 micro g/ml, P = 0.03) and rose uniformly in all subjects (12.2 +/- 2.3 vs. 25.7 +/- 2.6 micro g/ml, P < 10(-4)) after treatment, with no significant difference detected among the three groups [21].
• METHODS: Real-time RT-PCR, radioimmunoassay, Western blotting, radioligand binding and immunofluorescent analyses were applied to demonstrate the expression, secretion and functionality of placental adiponectin [3].
• The effects of recombinant adiponectin on osteoclasts formation also were examined in the co-culture systems of osteoblast and peripheral blood monocytes (PBMCs) systems or purified CD14 + PBMCs cultures [27].
• The complex aetiology of Type 2 diabetes, which probably involves a medley of molecular mechanisms, requires dissection out of diabetes-associated subphenotypes, such as the non-obese with increased liver fat or the obese with low plasma adiponectin [36].
• MS+ subjects had significantly lower adiponectin (7.6 +/- 0.6 vs. 10.4 +/- 0.6 microg/ml; P = 0.003) and significantly higher TNF-alpha (3.3 +/- 0.2 vs. 2.8 +/- 0.3 pg/ml; P = 0.004) levels compared with MS- subjects matched for age and body mass index [5].

References