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Satoshi Tetsumoto,
Yoshito Takeda,
Hirohiko Imai,
Atsuomi Kimura,
Yingji Jin,
Kaori Nakanishi,
Yohei Maeda,
Hanako Kuhara,
Kazuyuki Tsujino,
Takeo Iwasaki, [......],
Izumi Nagatomo,
Koji Inoue,
Hiroshi Kida,
Takashi Kijima,
Isao Tachibana, Norikazu Maeda,
Toru Funahashi,
Iichiro Shimomura,
Hideaki Fujiwara,
Atsushi Kumanogoh
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ABSTRACT: Animal disease models are pivotal to investigate the pathogenesis of emphysema and develop novel drugs, but the modalities used to evaluate murine emphysema models have limited validity and sensitivity. In this study, we evaluated hyperpolarized 129Xe magnetic resonance imaging (MRI) and micro-computed tomography (CT) compared to traditional methods, such as plethysmography and histology. Elastase-treated mice and adiponectin knockout mice were used as murine emphysema models to evaluate these modalities. Three weeks after elastase administration, significant and heterogeneous emphysema was evaluated based on the mean linear intercept and plethysmography parameters. Notably, the distribution of low-density areas, which was examined by micro-CT, correlated with the mean linear intercept and plethysmography parameters in whole lungs. These correlations were also observed in regional areas. Furthermore, we introduced hyperpolarized 129Xe MRI, which can evaluate gas exchange between alveoli and blood during spontaneous breathing. Parameters of gas exchange (fD) and alveolar size (Vs/Va) were significantly decreased in elastase-treated mice and moderately correlated with the plethysmography parameters. Of importance, we could detect a decrease in the fD value in low-density areas by micro-CT, suggesting that gas exchange decreased in emphysematous lesions. Likewise, these parameters (fD and Vs/Va) were also decreased in adiponectin knockout mice, which exhibit emphysema with a homogeneous distribution. We demonstrated the feasibility of 129Xe MRI and micro-CT in combination with traditional modalities. These non-invasive modalities provide complementary data that can be used to repeatedly estimate regional gas exchange and lung morphology.
American Journal of Respiratory Cell and Molecular Biology 05/2013; · 5.13 Impact Factor
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Masaya Yamaoka, Norikazu Maeda,
Seiji Nakamura,
Takuya Mori,
Kana Inoue,
Keisuke Matsuda,
Ryohei Sekimoto,
Susumu Kashine,
Yasuhiko Nakagawa,
Yu Tsushima,
Yuya Fujishima,
Noriyuki Komura,
Ayumu Hirata,
Hitoshi Nishizawa,
Yuji Matsuzawa,
Ken-Ichi Matsubara,
Tohru Funahashi,
Iichiro Shimomura
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ABSTRACT: OBJECTIVE: Visceral fat obesity is located upstream of metabolic syndrome and atherosclerotic diseases. Accumulating evidences indicate that several immunocytes including macrophages infiltrate into adipose tissue and induce chronic low-grade inflammation. We recently analyzed the association between visceral fat adiposity and the gene expression profile in peripheral blood cells in human subjects and demonstrated the close relationship of visceral fat adiposity and disturbance of circadian rhythm in peripheral blood cells. In a series of studies, we herein investigated the association of visceral fat adiposity and mRNA levels relating to inflammatory genes in peripheral blood cells. APPROACH AND RESULTS: Microarray analysis was performed in peripheral blood cells from 28 obese subjects. Reverse transcription-polymerase chain reaction (RT-PCR) was conducted by using blood cells from 57 obese subjects. Obesity was defined as body mass index (BMI) greater than 25 kg/m(2) according to the Japanese criteria. Gene expression profile analysis was carried out with Agilent whole human genome 4×44 K oligo-DNA microarray. Gene ontology (GO) analysis showed that 14 genes were significantly associated with visceral fat adiposity among 239 genes relating to inflammation. Among 14 genes, RT-PCR demonstrated that S100A8, S100A9, and S100A12 positively correlated with visceral fat adiposity in 57 subjects. Stepwise multiple regression analysis showed that S100A8 and S100A12 mRNA levels were closely associated with HOMA-IR and S100A9 mRNA was significantly related to adiponectin and CRP. CONCLUSIONS: Peripheral blood mRNA levels of S100 family were closely associated with insulin resistance and inflammation.
Biochemical and Biophysical Research Communications 03/2013; · 2.48 Impact Factor
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ABSTRACT: Visceral fat accumulation is located upstream of metabolic syndrome. Recent progress in adipocyte biology has clarified the molecular mechanism for pathophysiology of metabolic syndrome and its related disorders. In this review we summarize adiponectin and AQP7 in the role of metabolic syndrome and cardiovascular diseases.
Endocrine Journal 01/2013; · 2.03 Impact Factor
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Yuya Fujishima, Norikazu Maeda,
Kana Inoue,
Susumu Kashine,
Hitoshi Nishizawa,
Ayumu Hirata,
Junji Kozawa,
Tetsuyuki Yasuda,
Kohei Okita,
Akihisa Imagawa,
Tohru Funahashi,
Iichiro Shimomura
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ABSTRACT: We recently reported that short-term treatment with liraglutide (20.0 ± 6.4 days) reduced body weight and improved some scales of eating behavior in Japanese type 2 diabetes inpatients. However, it remained uncertain whether such liraglutide-induced improvement is maintained after discharge from the hospital. The aim of the present study was to determine the long-term effects of liraglutide on body weight, glycemic control, and eating behavior in Japanese obese type 2 diabetics.
Patients with obesity (body mass index (BMI) >25 kg/m2) and type 2 diabetes were hospitalized at Osaka University Hospital between November 2010 and December 2011. BMI and glycated hemoglobin (HbA1c) were examined on admission, at discharge and at 1, 3, and 6 months after discharge. For the liraglutide group (BMI; 31.3 ± 5.3 kg/m2, n = 29), patients were introduced to liraglutide after correction of hyperglycemic by insulin or oral glucose-lowering drugs and maintained on liraglutide after discharge. Eating behavior was assessed in patients treated with liraglutide using The Guideline For Obesity questionnaire issued by the Japan Society for the Study of Obesity, at admission, discharge, 3 and 6 months after discharge. For the insulin group (BMI; 29.1 ± 3.0 kg/m2, n = 28), each patient was treated with insulin during hospitalization and glycemic control maintained by insulin after discharge.
Liraglutide induced significant and persistent weight loss from admission up to 6 months after discharge, while no change in body weight after discharge was noted in the insulin group. Liraglutide produced significant improvements in all major scores of eating behavior questionnaire items and such effect was maintained at 6 months after discharge. Weight loss correlated significantly with the decrease in scores for recognition of weight and constitution, sense of hunger, and eating style.
Liraglutide produced meaningful long-term weight loss and significantly improved eating behavior in obese Japanese patients with type 2 diabetes.
Cardiovascular Diabetology 09/2012; 11:107. · 3.35 Impact Factor
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Nippon rinsho. Japanese journal of clinical medicine 05/2012; 70 Suppl 3:486-9.
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ABSTRACT: Mineralocorticoid receptor (MR) blockade ameliorated insulin resistance with improvements in adipocytokine dysregulation, inflammation, and excess of reactive oxygen species (ROS) in obese adipose tissue and adipocytes, but its mechanism has not been clarified. The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), producing active glucocorticoids, is highly expressed in adipocytes and glucocorticoids bind to MR with higher affinity than to glucocorticoid receptor (GR). We investigated whether glucocorticoids effect on adipocytokines and ROS through MR in adipocytes. In addition, fat distributions of MR and GR were investigated in human subjects.
Corticoid receptors and their target genes were examined in adipose tissue of obese db/db mice. 3T3-L1 adipocytes were treated with glucocorticoids, H(2)O(2), MR antagonist eplerenone (EP), GR antagonist RU486 (RU), MR-siRNA, and/or N-acetylcysteine. Human adipose tissues were obtained from seven patients who underwent abdominal surgery. The mRNA levels of MR and its target gene were higher in db/db mice than in control db/m+mice. In 3T3-L1 adipocytes, glucocorticoids, similar to H(2)O(2), caused the dysregulation of mRNA levels of various genes related to adipocytokines and the increase of intracellular ROS. Such changes were rectified by MR blockade, not by GR antagonist. In human fat, MR mRNA level was increased in parallel with the increase of body mass index (BMI) and its increase was more significant in visceral fat, while there were no apparent correlations of GR mRNA level to BMI or fat distribution.
Glucocorticoid-MR pathway may contribute to the obesity-related adipocytokine dysregulation and adipose ROS.
Biochemical and Biophysical Research Communications 02/2012; 419(2):182-7. · 2.48 Impact Factor
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Yukari Fujita,
Daisuke Tamada,
Junji Kozawa,
Yoko Kobayashi,
Shugo Sasaki,
Tetsuhiro Kitamura,
Tetsuyuki Yasuda, Norikazu Maeda,
Michio Otsuki,
Kohei Okita,
Hiromi Iwahashi,
Hideaki Kaneto,
Tohru Funahashi,
Akihisa Imagawa,
Iichiro Shimomura
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ABSTRACT: We herein describe a 59-year-old woman who had undergone a total gastrectomy for gastric carcinoma and suffered from postprandial hypoglycemia characterized by a loss of consciousness and spasms. She was diagnosed with reactive hypoglycemia and treated with nutrition therapy, but the frequency and severity of the hypoglycemic episodes did not decrease. She was subsequently treated successfully with miglitol, an alpha-glucosidase inhibitor (α-GI) taken twice a day; other α-GIs (acarbose and voglibose) were not effective. In conclusion, the administration of miglitol was effective for preventing reactive hypoglycemia secondary to late dumping syndrome.
Internal Medicine 01/2012; 51(18):2581-5. · 0.94 Impact Factor
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Masaya Yamaoka, Norikazu Maeda,
Seiji Nakamura,
Susumu Kashine,
Yasuhiko Nakagawa,
Aki Hiuge-Shimizu,
Kohei Okita,
Akihisa Imagawa,
Yuji Matsuzawa,
Ken-Ichi Matsubara,
Tohru Funahashi,
Iichiro Shimomura
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ABSTRACT: Evidence suggests that visceral fat accumulation plays a central role in the development of metabolic syndrome. Excess visceral fat causes local chronic low-grade inflammation and dysregulation of adipocytokines, which contribute in the pathogenesis of the metabolic syndrome. These changes may affect the gene expression in peripheral blood cells. This study for the first time examined the association between visceral fat adiposity and gene expression profile in peripheral blood cells. The gene expression profile was analyzed in peripheral blood cells from 28 obese subjects by microarray analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was performed using peripheral blood cells from 57 obese subjects. Obesity was defined as body mass index (BMI) greater than 25 kg/m(2) according to the Japanese criteria, and the estimated visceral fat area (eVFA) was measured by abdominal bioelectrical impedance. Analysis of gene expression profile was carried out with Agilent whole human genome 4×44 K oligo-DNA microarray. The expression of several genes related to circadian rhythm, inflammation, and oxidative stress correlated significantly with visceral fat accumulation. Period homolog 1 (PER1) mRNA level in blood cells correlated negatively with visceral fat adiposity. Stepwise multiple regression analysis identified eVFA as a significant determinant of PER1 expression. In conclusion, visceral fat adiposity correlated with the expression of genes related to circadian rhythm and inflammation in peripheral blood cells.
PLoS ONE 01/2012; 7(10):e47377. · 4.09 Impact Factor
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ABSTRACT: To examine the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, on visceral fat adiposity, appetite, food preference, and biomarkers of cardiovascular system in Japanese patients with type 2 diabetes.
The study subjects were 20 inpatients with type 2 diabetes treated with liraglutide [age; 61.2 ± 14.0 years, duration of diabetes; 16.9 ± 6.6 years, glycated hemoglobin (HbA1c); 9.1 ± 1.2%, body mass index (BMI); 28.3 ± 5.2 kg/m(2), mean ± SD]. After improvement in glycemic control by insulin or oral glucose-lowering agents, patients were switched to liraglutide. We assessed the estimated visceral fat area (eVFA) by abdominal bioelectrical impedance analysis, glycemic control by the 75-g oral glucose tolerance test (OGTT) and eating behavior by the Japan Society for the Study of Obesity questionnaire.
Treatment with liraglutide (dose range: 0.3 to 0.9 mg/day) for 20.0 ± 6.4 days significantly reduced waist circumference, waist/hip ratio, eVFA. It also significantly improved the scores of eating behavior, food preference and the urge for fat intake and tended to reduce scores for sense of hunger. Liraglutide increased serum C-peptide immunoreactivity and disposition index.
Short-term treatment with liraglutide improved visceral fat adiposity, appetite, food preference and the urge for fat intake in obese Japanese patients with type 2 diabetes.
Cardiovascular Diabetology 12/2011; 10:109. · 3.35 Impact Factor
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Naoto Katakami,
Hideaki Kaneto,
Taka-aki Matsuoka,
Mitsuyoshi Takahara, Norikazu Maeda,
Ikki Shimizu,
Keizo Ohno,
Takeshi Osonoi,
Koichi Kawai,
Fukashi Ishibashi,
Kenichi Imamura,
Atsunori Kashiwagi,
Ryuzo Kawamori,
Munehide Matsuhisa,
Tohru Funahashi,
Yoshimitsu Yamasaki,
Iichiro Shimomura
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ABSTRACT: Adiponectin has anti-atherogenic properties and reduced serum adiponectin levels are associated with cardiovascular disease (CVD). In this study, we examined the relationship between CVD and adiponectin (ADIPOQ) gene G276T polymorphism that is associated with serum adiponectin level in a large cohort of type 2 diabetic patients.
We enrolled 2637 Japanese type 2 diabetic subjects (males, 61.1%; age, 54.9±7.9 years old), determined their genotypes regarding ADIPOQ G276T polymorphisms, and evaluated the association between this polymorphism and the prevalence of CVD (myocardial infarction and/or cerebral infarction).
The prevalence of CVD tended to be higher as the number of G alleles increased [GG (9.5%), GT (6.8%), TT (5.6%), p value for trend=0.0059] and was significantly higher in the subjects with GG genotype compared to those with GT or TT genotype (9.5% vs. 6.6%, p=0.0060). Multiple logistic regression analyses revealed that the number of G alleles (Odds ratio (OR)=1.49 with 95%CI 1.09-2.05, p=0.0125) and GG genotype (OR=1.66 with 95%CI 1.13-2.43, p=0.0098) were significantly associated with CVD even after adjustment for conventional risk factors. Interestingly, the presence of obesity further and significantly increased the risk of CVD in the subjects with GG genotype (OR=1.67 with 95%CI 1.14-2.44, p=0.0090) but not in the subjects with TT or GT genotype (OR=1.17 with 95%CI 0.73-1.89, NS).
It is likely that the G allele of the ADIPOQ G276T polymorphism is a susceptibility allele for CVD in Japanese type 2 diabetic patients, especially when they accompany obesity.
Atherosclerosis 11/2011; 220(2):437-42. · 3.79 Impact Factor
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Yukiko Imanishi,
Shigeru Miyagawa, Norikazu Maeda,
Satsuki Fukushima,
Satoru Kitagawa-Sakakida,
Takashi Daimon,
Ayumu Hirata,
Tatsuya Shimizu,
Teruo Okano,
Iichiro Shimomura,
Yoshiki Sawa
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ABSTRACT: A drug delivery system that constitutively and effectively retains cardioprotective reagents in the targeted myocardium has long been sought to treat acute myocardial infarction. We hypothesized that a scaffold-free induced adipocyte cell-sheet (iACS), transplanted on the surface of the heart, might intramyocardially secrete multiple cardioprotective factors including adiponectin (APN), consequently attenuating functional deterioration after acute myocardial infarction.
Induced ACS were generated from adipose tissue-derived cells of wild-type (WT) mice (C57BL/6J), which secreted abundant APN, hepatocyte growth factor, and vascular endothelial growth factor in vitro. Transplanted iACS secreted APN into the myocardium of APN-knockout (KO) mice at 4 weeks. APN was also detected in the plasma of iACS-transplanted APN-KO mice at 3 months (245 ± 113 pg/mL). After left anterior descending artery ligation, iACS, generated from either WT (n=40) or APN-KO (n=40) mice, were grafted onto the surface of the anterior left ventricular wall of WT mice, or only left anterior descending artery ligation was performed (n=43). Two days later, inflammation and infarct size were significantly diminished only in the WT-iACS treated mice. One month later, cardiomyocyte diameter and percent fibrosis were smaller, whereas ejection fraction and survival were greater in the WT-iACS treated mice compared with the KO-iACS-treated or nontreated mice.
Cardioprotective factors including APN, hepatocyte growth factor, and vascular endothelial growth factor were secreted from iACS. Transplantation of iACS onto the acute myocardial infarction heart attenuated infarct size, inflammation, and left ventricular remodeling, mediated by intramyocardially secreted APN in a constitutive manner. This method might be a novel drug delivery system to treat heart disease.
Circulation 09/2011; 124(11 Suppl):S10-7. · 14.74 Impact Factor
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Nihon Naika Gakkai Zasshi 04/2011; 100(4):911-6.
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Nippon rinsho. Japanese journal of clinical medicine 01/2011; 69 Suppl 1:325-30.
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Kana Inoue,
Junji Kozawa,
Tohru Funahashi,
Yukiko Nakata,
Eri Mitsui,
Tetsuhiro Kitamura, Norikazu Maeda,
Ken Kishida,
Michio Otsuki,
Kohei Okita,
Hiromi Iwahashi,
Akihisa Imagawa,
Iichiro Shimomura
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ABSTRACT: Acute suppurative thyroiditis is a rare disorder that is mostly found in the left lobe of the thyroid gland of children due to congenital patency of the pyriform sinus fistula. Here, we report a 61-year-old man with acute right-sided suppurative thyroiditis without pyriform sinus fistula. He also showed infectious hip arthritis, spondylitis and Roth's spots. He presented with heart failure and was diagnosed with infectious endocarditis by sequential transesophageal echocardiography. A replacement with a prosthetic valve was performed and cured him. It is important to recognize that infectious endocarditis can be a focus of acute suppurative thyroiditis.
Internal Medicine 01/2011; 50(23):2893-7. · 0.94 Impact Factor
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Kaori Nakanishi,
Yoshito Takeda,
Satoshi Tetsumoto,
Takeo Iwasaki,
Kazuyuki Tsujino,
Hanako Kuhara,
Yingji Jin,
Izumi Nagatomo,
Hiroshi Kida,
Sho Goya,
Takashi Kijima, Norikazu Maeda,
Tohru Funahashi,
Iichiro Shimomura,
Isao Tachibana,
Ichiro Kawase
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ABSTRACT: Chronic obstructive pulmonary disease is frequently complicated with comorbidities, such as cardiovascular disease, osteoporosis, and body weight loss, but the causal link remains unclear.
To investigate the role of adiponectin in the pathogenesis of chronic obstructive pulmonary disease and its potential use in therapy.
Adiponectin localization and dynamics in the lung were analyzed in an elastase-induced emphysema model. Next, the lung of adiponectin-knockout mice, extrapulmonary effects, and the underlying mechanism were investigated. Finally, we tested whether exogenous adiponectin could ameliorate the emphysematous change in adiponectin-knockout mice.
Adiponectin expression in lung vasculature and plasma concentration of adiponectin were reduced after elastase-instillation. Notably, adiponectin-knockout mice showed progressive alveolar enlargement and increased lung compliance. They further exhibited not only systemic inflammation, but also extrapulmonary phenotype, such as body weight loss, fat atrophy, and osteoporosis. Moreover, endothelial apoptosis was enhanced in the lungs of adiponectin-knockout mice, as evidenced by caspase-3 activity. Consistent with this, expressions of vascular endothelial growth factor receptor-2 and platelet endothelial cell adhesion molecule-1 on endothelial cells were decreased in the adiponectin-knockout mice. Finally, adenovirus-mediated adiponectin supplementation ameliorated the emphysematous phenotype.
Adiponectin-knockout mice develop progressive chronic obstructive pulmonary disease-like phenotype with systemic inflammation and extrapulmonary phenotypes. Hypoadiponectinemia could thus play a critical role in the progression of chronic obstructive pulmonary disease and concomitant comorbidities through endothelial dysfunction. Together, adiponectin could be a novel target for chronic obstructive pulmonary disease therapy.
American Journal of Respiratory and Critical Care Medicine 01/2011; 183(9):1164-75. · 11.08 Impact Factor
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ABSTRACT: Accumulating evidence indicates that the regimen to increase adiponectin will provide a novel therapeutic strategy for metabolic syndrome. Here, we tested the effect of a potent and selective peroxisome proliferator-activated receptor-γ agonist, rivoglitazone (Rivo), a newly synthesized thiazolidinedione derivative, on adiponectin, insulin resistance, and atherosclerosis.
ob/ob mice, apolipoprotein E knockout (apoE KO) mice, and apoE and adiponectin double knockout mice were administered pioglitazone, Rivo, or no compound. Remarkable elevation of plasma adiponectin was observed, especially in Rivo-treated ob/ob mice. Rivo ameliorated insulin resistance in ob/ob mice and reduced atherosclerotic areas in apoE KO mice compared with the pioglitazone group but failed to decrease atherosclerotic areas in double knockout mice. Among adipose mRNAs, adipose S100A8, which activates Toll-like receptor 4-dependent signal transduction cascades and locates upstream of inflammation, was markedly increased in ob/ob mice, and its increase was completely reversed by Rivo treatment. In RAW264.7 macrophage cells and 3T3-L1 adipocytes, Rivo significantly reduced S100A8 mRNA levels.
The peroxisome proliferator-activated receptor-γ agonist Rivo remarkably enhanced adiponectin in plasma and decreased adipose S100A8 mRNA levels in obese mice. Rivo treatment apparently ameliorated insulin resistance in ob/ob mice and reduced atherosclerosis in apoE KO mice, partly through adiponectin.
Arteriosclerosis Thrombosis and Vascular Biology 01/2011; 31(4):792-9. · 6.37 Impact Factor
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ABSTRACT: Patients with chronic renal failure are at high risk of cardiovascular diseases. Previous studies in healthy population showed that hypoadiponectinemia was associated with high cardiovascular disease risk. However, plasma adiponectin (APN) levels are increased in renal dysfunction. Therefore, the clinical significance of plasma APN level in patients with moderate renal dysfunction is controversial. The aim of this study was to determine the change of plasma APN levels in a mouse model of renal failure and the loss of vasculo-protective function of APN in the presence of high cystatin C levels.
Subtotal (5/6) nephrectomy was performed in APN-knockout (KO) mice and wild-type (WT) mice. The procedure in WT mice resulted in the significant increase of plasma APN and cystatin C levels. The clearance rate of APN was measured by injecting plasma from WT mice into KO mice. The clearance rate was significantly decreased in subtotal nephrectomized KO mice compared with sham-operated KO mice. Adiponectin protein and mRNA levels in adipose tissue were similar to subtotal nephrectomized and sham-operated mice. In cultured endothelial cells, at a high concentration corresponding to renal failure, cystatin C abolished the suppressive effects of APN on tumour necrosis factor alpha-induced expression of monocyte adhesion molecules.
Plasma APN increases in chronic renal failure, at least in part due to low clearance rate. High concentrations of cystatin C abolish the vasculo-protective effect of APN.
Cardiovascular research 06/2010; 86(3):471-7. · 5.80 Impact Factor
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ABSTRACT: Atrial- and brain-type natriuretic peptides (ANP and BNP, respectively) have been shown to exert potent lipolytic action in adipocytes. A family of natriuretic peptide receptors (NPRs), NPR-1, NPR-2, and NPR-3, mediates their physiologic effects. NPR-1 and NPR-2 are receptor guanylyl cyclases, while NPR-3 lacks enzymatic activity and functions primarily as a clearance receptor for natriuretic peptides. ANP has a high affinity for NPR-1 and NPR-3 than other natriuretic peptides. There is a possibility that ANP may exhibit its lipolytic effect through the balance of NPR-1 and NPR-3 expressions in adipocytes. However, the regulation of adipose NPRs has not been fully elucidated. We here examined the regulation of mouse adipose NPRs by insulin, an anti-lipolytic hormone. Among the insulin target organs, NPR-1 mRNA levels were higher in white adipose tissue (WAT) than in liver and skeletal muscle. NPR-3 mRNA was expressed most abundantly in WAT. Fasting condition induced NPR-1 mRNA level while suppressed NPR-3 mRNA level in WAT. Administration of streptozotocin resulted in the increase of NPR-1 mRNA level while the decrease of NPR-3 mRNA level in WAT. In ob/ob mice, hyperinsulinemic model, NPR-1 mRNA level was lower whereas NPR-3 mRNA level was higher compared to lean control mice. In 3T3-L1 adipocytes, insulin significantly reduced NPR-1 mRNA level while increased NPR-3 mRNA levels both through phosphatidylinositol 3-kinase (PI3-kinase) pathway. In summary, NPR-1 and NPR-3 were highly expressed in WAT and adipose NPR-1 and NPR-3 were reciprocally regulated by insulin. This study suggests that insulin may efficiently promote lipogenesis partly by reducing the lipolytic action of ANP through the opposite regulation of NPR-1 and NPR-3.
Biochemical and Biophysical Research Communications 01/2010; 392(1):100-5. · 2.48 Impact Factor
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Koichi Fujita, Norikazu Maeda,
Junji Kozawa,
Kakeyoshi Murano,
Kohei Okita,
Hiromi Iwahashi,
Shinji Kihara,
Masato Ishigami,
Motoko Omura,
Tadashi Nakamura,
Kohji Shirai,
Taku Yamamura,
Tohru Funahashi,
Iichiro Shimomura
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ABSTRACT: Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) enhance the hydrolysis of triglycerides (TG) transported by chylomicron (CM) and very-low-density lipoprotein (VLDL). We report a case of severe hyperchylomicronemia with high levels of remnant lipoprotein and total cholesterol (T-Chol) in a 15-year-old boy. Precise examination of the lipid profile showed decreased activities of both LPL and HTGL, although the protein mass for LPL and HTGL were maintained. In addition, bezafibrate treatment effectively ameliorated hypertriglyceridemia in this case. This is the first case of hyperchylomicronemia with decreased activities and unaffected protein masses for both LPL and HTGL, without overt immuno-dysfunction.
Internal Medicine 01/2010; 49(22):2467-72. · 0.94 Impact Factor
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ABSTRACT: In obesity, chronic low-grade inflammation and overproduction of reactive oxygen species (ROS) in fat contribute to the development of metabolic syndrome. Suppression of inflammation and ROS production in fat may attenuate the metabolic syndrome. Activation of mineralocorticoid receptor (MR) promotes inflammation in heart, kidney, and vasculature via ROS generation. However, the significance of MR in fat remains elusive. Here we investigated whether MR blockade attenuates obesity-related insulin resistance and improves adipocyte dysfunction.
Obese ob/ob and db/db mice were treated with eplerenone, a MR antagonist, for 3 weeks. 3T3-L1 adipocytes were treated with aldosterone or H2O2, with and without eplerenone or MR-siRNA. High levels of MR mRNA were detected in adipose tissue of obese ob/ob and db/db mice. Eplerenone treatment significantly reduced insulin resistance, suppressed macrophage infiltration and ROS production in adipose tissues, and corrected the mRNA levels of obesity-related genes in obese mice. In 3T3-L1 adipocytes, aldosterone and H2O2 increased intracellular ROS levels and MR blockade inhibited such increases. H2O2 and aldosterone resulted in dysregulation of mRNAs of various genes related to ROS and cytokines, whereas MR blockade corrected such changes.
MR blockade attenuates obesity-related insulin resistance partly through reduction of fat ROS production, inflammatory process, and induction of cytokines.
Cardiovascular research 07/2009; 84(1):164-72. · 5.80 Impact Factor
