Biomedical subjects

Shinji Kihara

Publications and source records attributed to Shinji Kihara.

18 recordsLinked to original sources

PubMed2003

Association of hypoadiponectinemia with impaired vasoreactivity.

Endothelial dysfunction is a crucial feature in the evolution of atherosclerosis. Adiponectin is an adipocyte-specific plasma protein with antiatherogenic and antidiabetic properties. In the present study, we investigated the relation between adiponectin and endothelium-dependent vasodilation. We analyzed endothelial function in 202 hypertensive patients, including those who were not taking any medication. Forearm blood flow was measured by strain-gauge plethysmography. Plasma adiponectin level was highly correlated with the vasodilator response to reactive hyperemia in the total (r=0.257, P<0.001) and no-medication (r=0.296, P=0.026) groups but not with nitroglycerin-induced hyperemia, indicating that adiponectin affected endothelium-dependent vasodilation. Multiple regression analysis of data from all hypertensive patients revealed that plasma adiponectin level was independently correlated with the vasodilator response to reactive hyperemia. Vascular reactivity was also analyzed in aortic rings from adiponectin-knockout (KO) and wild-type (WT) mice. Adiponectin-KO mice showed obesity, hyperglycemia, and hypertension compared with WT mice after 4 weeks on an atherogenic diet. Endothelium-dependent vasodilation in response to acetylcholine was significantly reduced in adiponectin-KO mice compared with WT mice, although no significant difference was observed in endothelium-independent vasodilation in response to sodium nitroprusside. Our observations suggest that hypoadiponectinemia is associated with impaired endothelium-dependent vasorelaxation and that the measurement of plasma adiponectin level might be helpful as a marker of endothelial dysfunction.

Acetylcholine↗

PubMed2003

Disturbed secretion of mutant adiponectin associated with the metabolic syndrome.

Adiponectin, an adipocyte-derived protein, consists of collagen-like fibrous and complement C1q-like globular domains, and circulates in human plasma in a multimeric form. The protein exhibits anti-diabetic and anti-atherogenic activities. However, adiponectin plasma concentrations are low in obese subjects, and hypoadiponectinemia is associated with the metabolic syndrome, which is a cluster of insulin resistance, type 2 diabetes mellitus, hypertension, and dyslipidemia. We have recently reported a missense mutation in the adiponectin gene, in which isoleucine at position 164 in the globular domain is substituted with threonine (I164T). Subjects with this mutation showed markedly low level of plasma adiponectin and clinical features of the metabolic syndrome. Here, we examined the molecular characteristics of the mutant protein associated with a genetic cause of hypoadiponectinemia. The current study revealed (1) the mutant protein showed an oligomerization state similar to the wild-type as determined by gel filtration chromatography and, (2) the mutant protein exhibited normal insulin-sensitizing activity, but (3) pulse-chase study showed abnormal secretion of the mutant protein from adipose tissues. Our results suggest that I164T mutation is associated with hypoadiponectinemia through disturbed secretion into plasma, which may contribute to the development of the metabolic syndrome.

Adiponectin↗

PubMed2003

Measurement of fasting serum apoB-48 levels in normolipidemic and hyperlipidemic subjects by ELISA.

The present study was designed to evaluate the metabolism of chylomicron and chylomicron remnants by measuring serum apolipoprotein B-48 (apoB-48) levels in 335 normolipidemic and 253 hyperlipidemic subjects using a novel ELISA system. The distribution of fasting serum apoB-48 levels in normolipidemic subjects varied widely, ranging from <1 to >24 microgram/ml (mean, 5.2 +/- 3.8 microgram/ml; median, 3.9 microgram/ml). Serum apoB-48 levels correlated with serum triglyceride (TG) concentrations (r = 0.45, P < 0.001), but not with total cholesterol levels. Serum apoB-48 levels were 7 to 18 times higher in patients with Type I, Type V, and Type III hyperlipidemia, and only slightly higher in patients with Type IIa, Type IIb, and Type IV hyperlipidemia, compared with normolipidemic subjects. The calculated apoB-48/TG ratio was elevated only in patients with dysbetalipoproteinemia (apoE2/2 phenotype). In normolipidemic subjects, oral fat loading resulted in about 2-fold increase in serum apoB-48 levels, with a peak level recorded at 3-4 h postloading, and then returned to the baseline level within 6 h. On the other hand, in patients with dysbetalipoproteinemia, serum apoB-48 levels did not change considerably. Our results indicate that serum apoB-48 is a very useful parameter for evaluating lipoprotein metabolism in exogenous pathways.

Adult↗

PubMed2003

Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue.

BACKGROUND: High-sensitive C-reactive protein (hs-CRP) is a well-known risk factor for coronary artery disease (CAD). Recently, we have demonstrated that adiponectin served as an antiatherogenic plasma protein which was secreted specifically from adipocytes. The present study investigated the association between adiponectin and CRP in the blood stream and adipose tissue. METHODS AND RESULTS: We studied a total of 101 male patients, 71 of whom had angiographically documented coronary atherosclerosis. As a control group, 30 patients with normal coronary angiogram were included. The plasma hs-CRP levels were negatively correlated with the plasma adiponectin levels (r=-0.29, P<0.01). The plasma adiponectin concentrations were significantly lower and the hs-CRP levels were significantly higher in the CAD patients compared with control subjects. The mRNA levels of CRP and adiponectin were analyzed by quantitative real-time polymerase chain reaction method. We found that the CRP mRNA was expressed in human adipose tissue. A significant inverse correlation was observed between the CRP and adiponectin mRNA levels in human adipose tissue (r=-0.89, P<0.01). In addition, the CRP mRNA level of white adipose tissue in adiponectin deficient mice was higher than that of wild-type mice. CONCLUSIONS: The reciprocal association of adiponectin and CRP levels in both human plasma and adipose tissue might participate in the development of atherosclerosis.

Adiponectin↗

PubMed2003

Association of hypoadiponectinemia with coronary artery disease in men.

BACKGROUND: Adiponectin is an adipocyte-derived plasma protein that accumulates in the injured artery and has potential antiatherogenic properties. This study was designed to determine whether a decreased plasma adiponectin level (hypoadiponectinemia) can be independently associated with the prevalence of coronary artery disease (CAD). METHODS AND RESULTS: The consecutive 225 male patients were enrolled from inpatients who underwent coronary angiography. Voluntary blood donors (n=225) matched for age served as controls. Plasma adiponectin levels in the CAD patients were significantly lower than those in the control subjects. Multiple logistic regression analysis including plasma adiponectin level, diabetes mellitus, dyslipidemia, hypertension, smoking habits, and body mass index revealed that hypoadiponectinemia was significantly and independently correlated with CAD (P<0.0088). The entire study population was categorized in quartiles based on the distribution of plasma adiponectin levels. The interquartile cutoff points were 4.0, 5.5, and 7.0 microg/mL. The multivariate-adjusted odds ratios for CAD in the first, second, and third quartiles were 2.051 (95% confidence interval [CI], 1.288 to 4.951), 1.221 (95% CI, 0.684 to 2.186), and 0.749 (95%CI, 0.392 to 1.418), respectively. CONCLUSIONS: Male patients with hypoadiponectinemia (<4.0 microg/mL) had a significant 2-fold increase in CAD prevalence, independent of well-known CAD risk factors.

Adiponectin↗

PubMed2003

Adiponectin is markedly increased in patients with nephrotic syndrome and is related to metabolic risk factors.

BACKGROUND: Adiponectin (ADPN), the gene product of apM1, is the most abundant secretory protein of the adipose tissue in human plasma. Altered regulation (reduced synthesis) of this substance may be relevant to endothelial dysfunction and cardiovascular complications in patients with ESRD. METHODS: We investigated the relationship between plasma ADPN, glomerular filtration rate (GFR) (plasma iohexol clearance), and metabolic risk factors in 16 patients with nephrotic syndrome, in 25 patients with chronic nephropathies without nephrotic syndrome, and in 31 healthy subjects. RESULTS: Plasma ADPN was much higher (P < 0.01) in patients with nephrotic syndrome (24.4 +/- 14.9 microg/mL) than in patients with chronic nephropathies without nephrotic syndrome (12.3 +/- 7.2 microg/mL) and healthy subjects (5.9 +/- 2.6 microg/mL). In the aggregate 24-hour, proteinuria (r = 0.53, P < 0.01) and serum cholesterol (r = 0.53, P < 0.01) were strong and direct correlates of plasma ADPN, while serum albumin correlated inversely (r = -0.46, P < 0.01) with this protein. Proteinuria appeared to be an important confounder of the relationship between ADPN and the GFR because in the whole patient population (with and without nephrotic syndrome), this relationship emerged only after data adjustment for 24-hour proteinuria (partial r = -0.31, P = 0.05), while no such relationship was demonstrable on crude data analysis (r = 0.03, P = 0.87). CONCLUSIONS: ADPN is markedly increased in patients with nephrotic syndrome, and proteinuria is strongly related to circulating ADPN in patients with nephrotic and non-nephrotic renal diseases. The relationships between plasma ADPN, serum cholesterol, and serum albumin suggest that this adipocyte protein may serve to mitigate endothelial damage triggered by dyslipidemia and other risk factors in patients with chronic renal diseases.

Adiponectin↗

PubMed2002

Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice.

BACKGROUND: Dysregulation of adipocyte-derived bioactive molecules plays an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipocyte-specific plasma protein, accumulated in the injured artery from the plasma and suppressed endothelial inflammatory response and vascular smooth muscle cell proliferation, as well as macrophage-to-foam cell transformation in vitro. The current study investigated whether the increased plasma adiponectin could actually reduce atherosclerosis in vivo. METHODS AND RESULTS: Apolipoprotein E-deficient mice were treated with recombinant adenovirus expressing human adiponectin (Ad-APN) or beta-galactosidase (Ad-betagal). The plasma adiponectin levels in Ad-APN-treated mice increased 48 times as much as those in Ad-betagal treated mice. On the 14th day after injection, the lesion formation in aortic sinus was inhibited in Ad-APN-treated mice by 30% compared with Ad-betagal-treated mice (P<0.05). In the lesions of Ad-APN-treated mice, the lipid droplets became smaller compared with Ad-betagal-treated mice (P<0.01). Immunohistochemical analyses demonstrated that the adenovirus-mediated adiponectin migrate to foam cells in the fatty streak lesions. The real-time quantitative polymerase chain reaction revealed that Ad-APN treatment significantly suppressed the mRNA levels of vascular cell adhesion molecule-1 by 29% and class A scavenger receptor by 34%, and tended to reduce levels of tumor necrosis factor-alpha without affecting those of CD36 in the aortic tissue. CONCLUSIONS: These findings documented for the first time that elevated plasma adiponectin suppresses the development of atherosclerosis in vivo.

Adiponectin↗

PubMed2002

Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis.

Obesity is more linked to vascular disease, including atherosclerosis and restenotic change, after balloon angioplasty. The precise mechanism linking obesity and vascular disease is still unclear. Previously we have demonstrated that the plasma levels of adiponectin, an adipose-derived hormone, decreases in obese subjects, and that hypoadiponectinemia is associated to ischemic heart disease. In current the study, we investigated the in vivo role of adiponectin on the neointimal thickening after artery injury using adiponectin-deficient mice and adiponectin-producing adenovirus. Adiponectin-deficient mice showed severe neointimal thickening and increased proliferation of vascular smooth muscle cells in mechanically injured arteries. Adenovirus-mediated supplement of adiponectin attenuated neointimal proliferation. In cultured smooth muscle cells, adiponectin attenuated DNA synthesis induced by growth factors including platelet-derived growth factor, heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), basic fibroblast growth factor, and EGF and cell proliferation and migration induced by HB-EGF. In cultured endothelial cells, adiponectin attenuated HB-EGF expression stimulated by tumor necrosis factor alpha. The current study suggests an adipo-vascular axis, a direct link between fat and artery. A therapeutic strategy to increase plasma adiponectin should be useful in preventing vascular restenosis after angioplasty.

Adenoviridae↗

PubMed2002

Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell.

BACKGROUND: Vascular smooth muscle cell proliferation plays an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipocyte-specific plasma protein, accumulated in the human injured artery and suppressed endothelial inflammatory response as well as macrophage-to-foam cell transformation. The present study investigated the effects of adiponectin on proliferation and migration of human aortic smooth muscle cells (HASMCs). Methods and Results- HASMC proliferation was estimated by [(3)H] thymidine uptake and cell number. Cell migration assay was performed using a Boyden chamber. Physiological concentrations of adiponectin significantly suppressed both proliferation and migration of HASMCs stimulated with platelet-derived growth factor (PDGF)-BB. Adiponectin specifically bound to (125)I-PDGF-BB and significantly inhibited the association of (125)I-PDGF-BB with HASMCs, but no effects were observed on the binding of (125)I-PDGF-AA or (125)I-heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) to HASMCs. Adiponectin strongly and dose-dependently suppressed PDGF-BB-induced p42/44 extracellular signal-related kinase (ERK) phosphorylation and PDGF beta-receptor autophosphorylation analyzed by immunoblot. Adiponectin also reduced PDGF-AA-stimulated or HB-EGF-stimulated ERK phosphorylation in a dose-dependent manner without affecting autophosphorylation of PDGF alpha-receptor or EGF receptor. CONCLUSIONS: The adipocyte-derived plasma protein adiponectin strongly suppressed HASMC proliferation and migration through direct binding with PDGF-BB and generally inhibited growth factor-stimulated ERK signal in HASMCs, suggesting that adiponectin acts as a modulator for vascular remodeling.

Adipocytes↗

PubMed2002

Diet-induced insulin resistance in mice lacking adiponectin/ACRP30.

Here we investigated the biological functions of adiponectin/ACRP30, a fat-derived hormone, by disrupting the gene that encodes it in mice. Adiponectin/ACRP30-knockout (KO) mice showed delayed clearance of free fatty acid in plasma, low levels of fatty-acid transport protein 1 (FATP-1) mRNA in muscle, high levels of tumor necrosis factor-alpha (TNF-alpha) mRNA in adipose tissue and high plasma TNF-alpha concentrations. The KO mice exhibited severe diet-induced insulin resistance with reduced insulin-receptor substrate 1 (IRS-1)-associated phosphatidylinositol 3 kinase (PI3-kinase) activity in muscle. Viral mediated adiponectin/ACRP30 expression in KO mice reversed the reduction of FATP-1 mRNA, the increase of adipose TNF-alpha mRNA and the diet-induced insulin resistance. In cultured myocytes, TNF-alpha decreased FATP-1 mRNA, IRS-1-associated PI3-kinase activity and glucose uptake, whereas adiponectin increased these parameters. Our results indicate that adiponectin/ACRP30 deficiency and high TNF-alpha levels in KO mice reduced muscle FATP-1 mRNA and IRS-1-mediated insulin signaling, resulting in severe diet-induced insulin resistance.

Adiponectin↗

PubMed2002

Increased plasma HB-EGF associated with obesity and coronary artery disease.

The mechanism by which the obese subjects are more associated with vascular disease remains unclear. We reported that the adipose tissues produce and secrete many bioactive molecules, conceptualized as adipocytokines. Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), produced locally by vascular macrophages and smooth muscle cells, has been suggested to induce the migration and proliferation of vascular smooth muscle cells. The current study reveals that (1) HB-EGF mRNA is abundantly expressed in human adipose tissue, (2) HB-EGF mRNA increases in the fat tissues of obese mice, (3) plasma HB-EGF levels increase in parallel with fat accumulation in human, and (4) the subjects with coronary artery disease have higher plasma HB-EGF levels, associated with fat accumulation. These results suggest that increased plasma HB-EGF derived from the accumulated fat contributes to the higher incidence of vascular disease in obesity, proposing HB-EGF as an adipocytokine directly linking adipovascular axis.

Adipose Tissue↗

PubMed2002

Human aquaporin adipose (AQPap) gene. Genomic structure, promoter analysis and functional mutation.

Aquaporin adipose (AQPap), which we identified from human adipose tissue, is a glycerol channel in adipocyte [Kishida et al. (2000) J. Biol. Chem. 275, 20896-20902]. In the current study, we determined the genomic structure of the human AQPap gene, and identified three AQPap-like genes that resembled (approximately 95%) AQPap, with little expression in human tissues. The AQPap promoter contained a putative peroxisome proliferator response element (PPRE) at -46 to -62, and a putative insulin response element (IRE) at -542/-536. Deletion of the PPRE abolished the pioglitazone-mediated induction of AQPap promoter activity in 3T3-L1 adipocytes. Deletion and single base pair substitution analysis of the IRE abolished the insulin-mediated suppression of the human AQPap gene. Analysis of AQPap sequence in human subjects revealed three missense mutations (R12C, V59L and G264V), and two silent mutations (A103A and G250G). The cRNA injection of the missense mutants into Xenopus oocytes revealed the absence of the activity to transport glycerol and water in the AQPap-G264V protein. In the subject homozygous for AQPap-G264V, exercise-induced increase in plasma glycerol was not observed in spite of the increased plasma noradrenaline. We suggest that AQPap is responsible for the increase of plasma glycerol during exercise in humans.

Aquaporins↗

PubMed2002

Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease.

Adiponectin (ADPN), which is a secretory protein of adipose tissue, attenuates endothelial inflammatory responses in vitro. Among human subjects, plasma ADPN concentrations are reduced among patients with atherosclerotic complications but are substantially increased among patients with advanced renal failure. The clinical and biochemical correlates of plasma ADPN levels were investigated and the predictive power of ADPN levels with respect to survival rates and cardiovascular events was prospectively tested in a cohort of 227 hemodialysis patients, who were monitored for 31 +/- 13 mo. Plasma ADPN levels were 2.5 times higher (P < 0.0001) among dialysis patients (15.0 +/- 7.7 microg/ml) than among healthy subjects (6.3 +/- 2.0 microg/ml), were independent of age, and were higher (P = 0.03) among women (15.2 +/- 7.9 microg/ml) than among men (14.0 +/- 7.4 microg/ml). For both genders, plasma ADPN levels were inversely related to body mass index values, plasma leptin levels, insulin levels, serum triglyceride levels, and homeostatic model assessment index values. Furthermore, plasma ADPN levels were directly related to HDL cholesterol levels and inversely related to von Willebrand factor levels. Plasma ADPN levels were lower (P < 0.05) among patients who experienced new cardiovascular events (13.7 +/- 7.3 microg/ml) than among event-free patients (15.8 +/- 7.8 microg/ml). There was a 3% risk reduction for each 1 microg/ml increase in plasma ADPN levels, and the relative risk of adverse cardiovascular events was 1.56 times (95% confidence interval, 1.12 to 1.99 times) higher among patients in the first ADPN tertile, compared with those in the third tertile. Plasma ADPN levels are an inverse predictor of cardiovascular outcomes among patients with end-stage renal disease. Furthermore, ADPN is related to several metabolic risk factors in a manner consistent with the hypothesis that this protein acts as a protective factor for the cardiovascular system.

Adiponectin↗

PubMed2002

Coordinated regulation of fat-specific and liver-specific glycerol channels, aquaporin adipose and aquaporin 9.

Plasma glycerol is a major substrate for hepatic gluconeogenesis. Aquaporin adipose (AQPap/7), an adipose-specific glycerol channel, provides fat-derived glycerol into plasma. In the present study, we cloned the coding and promoter regions of mouse aquaporin 9 (AQP9), a liver-specific glycerol channel. Fasting and refeeding of mice increased and decreased hepatic AQP9 mRNA levels, respectively. Insulin deficiency induced by streptozotocin resulted in increased hepatic AQP9 mRNA. These changes in hepatic AQP9 mRNA were accompanied by those of hepatic gluconeogenic mRNAs and plasma glycerol levels. In cultured hepatocytes, insulin downregulated AQP9 mRNA. The AQP9 promoter contained the negative insulin response element TGTTTTC at -496/-502, similar to the promoter of the AQPap/7 gene. In contrast, in insulin-resistant db+/db+ mice, AQPap/7 mRNA in fat and AQP9 mRNA in liver were increased, despite hyperinsulinemia, with high plasma glycerol and glucose levels. Glycerol infusion in the db+/db+ mice augmented hepatic glucose output. Our results indicate that coordinated regulations of fat-specific AQPap/7 and liver-specific AQP9 should be crucial to determine glucose metabolism in physiology and insulin resistance.

Amino Acid Sequence↗

PubMed2002

Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome.

Adiponectin, also referred to as AdipoQ or ACRP30, is a plasma protein produced and secreted exclusively from adipose tissue. The protein contains a collagen-like domain and a C1q-like globular domain. A protease-generated globular segment enhances fatty acid oxidation in muscles, thereby modulating lipid and glucose metabolism. Plasma adiponectin levels are inversely correlated with the severity of insulin resistance. A recent genome-wide scan study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. Here, we screened Japanese patients with type 2 diabetes and age- and BMI-matched nondiabetic control subjects for mutations in adiponectin gene. We identified four missense mutations (R112C, I164T, R221S, and H241P) in the globular domain. Among these mutations, the frequency of I164T mutation was significantly higher in type 2 diabetic patients than in age- and BMI- matched control subjects (P < 0.01). Furthermore, plasma adiponectin concentrations of subjects carrying I164T mutation were lower than those of subjects without the mutation. All the subjects carrying I164T mutation showed some feature of metabolic syndrome, including hypertension, hyperlipidemia, diabetes, and atherosclerosis. Our findings suggest that I164T mutation is associated with low plasma adiponectin concentration and type 2 diabetes.

Adiponectin↗

PubMed2002

Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein.

Adiponectin, an adipose-specific secretory protein, exhibits antidiabetic and antiatherogenic properties. In the present study, we examined the effects of sex hormones on the regulation of adiponectin production. Plasma adiponectin concentrations were significantly lower in 442 men (age, 52.6 +/- 11.9 years [mean +/- SD]) than in 137 women (53.2 +/- 12.0 years) but not different between pre- and postmenopausal women. In mice, ovariectomy did not alter plasma adiponectin levels. In contrast, high levels of plasma adiponectin were found in castrated mice. Testosterone treatment reduced plasma adiponectin concentration in both sham-operated and castrated mice. In 3T3-L1 adipocytes, testosterone reduced adiponectin secretion into the culture media, using pulse-chase study. Castration-induced increase in plasma adiponectin was associated with a significant improvement of insulin sensitivity. Our results indicate that androgens decrease plasma adiponectin and that androgen-induced hypoadiponectinemia may be related to the high risks of insulin resistance and atherosclerosis in men.

3T3 Cells↗

PubMed2001

Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation.

Small heterodimer partner (SHP, NR0B2) is an atypical orphan nuclear receptor that inhibits transcriptional activation by several other nuclear receptors. We recently reported that mutations in the SHP gene are associated with insulin resistance. In the present study, we demonstrated that the SHP gene is expressed in adipose tissues. A reporter gene assay showed that a gene product of SHP increased the transcriptional activation of peroxisome proliferator-activated receptor (PPAR) gamma. SHP-mediated activation of PPARgamma was observed both in the presence and absence of the ligand of PPARgamma. Immunoprecipitation and glutathione S-transferase pull-down assay showed that SHP directly bound to PPARgamma and competed with nuclear receptor corepressor for binding to PPARgamma. Serial deletion studies indicated that the C terminus of SHP is important for PPARgamma activation. Mutant SHP proteins, which are found in naturally occurring mutation, showed less enhancing activity for PPARgamma than wild-type SHP. Our results suggest that SHP may act as an endogenous enhancer of PPARgamma.

Animals↗

PubMedDate not supplied

Adiponectin in essential hypertension.

Adiponectin (ADPN), the gene product of apM1, is the most abundant secretory protein of adipose tissue in human plasma. Synthesis of this substance may be reduced in endothelial dysfunction and cardiovascular diseases in humans. We investigated the relationship between plasma ADPN, body mass index (BMI), fat mass (BIA) and renal function in 36 patients with uncomplicated essential hypertension. Plasma ADPN was higher in hypertensive patients than in normotensive subjects, but the difference just failed to reach statistical significance (P=0.06). Hypertensive men had significantly higher plasma ADPN than normotensive men (6.7+/-2.6 vs 4.8+/-2.0 microg/mL, 40%, P=0.01). By contrast, the difference between hypertensive (8.5+/-3.9 microg/mL) and normotensive women (7.1+/-2.6 microg/mL) was not significant (20%). In hypertensive patients, plasma ADPN was inversely related to creatinine clearance and tended to be inversely related to serum insulin (r= -0.27) and HOMA-R index (r= -0.24). The relationship between plasma ADPN and renal function was confirmed in a multiple regression analysis which showed that creatinine clearance was the only independent predictor of plasma ADPN. Plasma ADPN in essential hypertension is dependent on sex and renal function. High levels in essential hypertensives may be the expression of a counter-regulatory response aimed at mitigating endothelial damage and cardiovascular risk associated with high arterial pressure.

Adiponectin↗