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Michio Shimabukuro,
Chisayo Kozuka,
Shin-Ichiro Taira,
Koichi Yabiku,
Munkhbaatar Dagvasumberel,
Masayoshi Ishida,
Sachiko Matsumoto,
Shusuke Yagi,
Daiju Fukuda,
Ken Yamakawa,
Moritake Higa,
Takeshi Soeki,
Hisashi Yoshida, Hiroaki Masuzaki,
Masataka Sata
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ABSTRACT: The obesity epidemic is a global public health concern that increases the likelihood of morbidity and mortality of metabolic and cardiovascular disease (CVD) and threatens to reduce life expectancy around the world. The concept of the metabolic syndrome (MetS) takes into account that visceral fat plays an essential role in the development of metabolic and cardiovascular diseases. However, MetS cannot be used to assess global CVD risk but is at best one more modifiable CVD risk factor. Thus, global cardiometabolic risk (the global risk of cardiovascular disease resulting from traditional risk factors combined with the additional contribution of the metabolic syndrome and/or insulin resistance) should be considered individually. There is solid evidence supporting the notion that excess abdominal fat is predictive of insulin resistance and the presence of related metabolic abnormalities currently referred to as MetS. Despite the fact that abdominal obesity is a highly prevalent feature of MetS, the mechanisms by which abdominal obesity is causally related to MetS are not fully elucidated. Besides visceral fat accumulation, ectopic lipid deposition, especially in liver and skeletal muscle, has been implicated in the pathophysiology of diabetes, insulin resistance and obesity-related disorders. Also, ectopic fat deposition could be deteriorated in the heart components such as (1) circulatory and locally recruited fat, (2) intra- and extra-myocellular fat, (3) perivascular fat, and (4) pericardial fat. In this review, the contribution of ectopic lipid deposition to global cardiometabolic risk is reviewed and also discussed are potential underlying mechanisms including adipocytokine, insulin resistance and lipotoxicity. J. Med. Invest. 60: 1-14, February, 2013.
The Journal of Medical Investigation 01/2013; 60(1-2):1-14.
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Chisayo Kozuka,
Kouichi Yabiku,
Sumito Sunagawa,
Rei Ueda,
Shin-Ichiro Taira,
Hiroyuki Ohshiro,
Tomomi Ikema,
Ken Yamakawa,
Moritake Higa,
Hideaki Tanaka,
Chitoshi Takayama,
Masayuki Matsushita,
Seiichi Oyadomari,
Michio Shimabukuro, Hiroaki Masuzaki
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ABSTRACT: Brown rice is known to improve glucose intolerance and prevent the onset of diabetes. However, the underlying mechanisms remain obscure. In the current study, we investigated the effect of brown rice and its major component, γ-oryzanol (Orz), on feeding behavior and fuel homeostasis in mice. When mice were allowed free access to a brown rice-containing chow diet (CD) and a high-fat diet (HFD), they significantly preferred CD to HFD. To reduce hypothalamic endoplasmic reticulum (ER) stress on an HFD, mice were administered with 4-phenylbutyric acid, a chemical chaperone, which caused them to prefer the CD. Notably, oral administration of Orz, a mixture of major bioactive components in brown rice, also improved glucose intolerance and attenuated hypothalamic ER stress in mice fed the HFD. In murine primary neuronal cells, Orz attenuated the tunicamycin-induced ER stress. In luciferase reporter assays in human embryonic kidney 293 cells, Orz suppressed the activation of ER stress-responsive cis-acting elements and unfolded protein response element, suggesting that Orz acts as a chemical chaperone in viable cells. Collectively, the current study is the first demonstration that brown rice and Orz improve glucose metabolism, reduce hypothalamic ER stress, and consequently, attenuate the preference for dietary fat in mice fed an HFD.
Diabetes 07/2012; · 8.29 Impact Factor
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ABSTRACT: BACKGROUND/OBJECTIVES: Visceral fat obesity plays an essential role in the clustering of cardiovascular risk factors. This study aimed to clarify the effects of miglitol, α-glycosidase inhibitor, on body weight, fat distribution and cardiovascular risk factors in patients with the metabolic syndrome. METHODS AND RESULTS: One hundred and eleven drug naive patients with the metabolic syndrome were continuously recruited and randomly allocated to a group of life style modification (LSM) alone or a group of LSM with miglitol per os 50mg×3 (LSM+miglitol). After 12weeks of treatment, body weight (5.1%), body mass index (4.9%) and waist circumference were greatly reduced in miglitol group (n=42) than in LSM group (n=43). Plasma levels of insulin and glucose during an oral 75g glucose loading were decreased only in miglitol group. Visceral fat area, determined by abdominal computed tomography, was greatly reduced in miglitol group (baseline 188 vs 12weeks 161cm(2), p<0.0001) than in LSM group (184 vs 174cm(2), p<0.05). Subcutaneous fat area was reduced only in miglitol group (p<0.001). Systolic blood pressure was reduced in miglitol group (142 vs 133mm Hg, p<0.001), but not in control group (137 vs 134mm Hg). Serum levels of triglyceride, LDL-cholesterol, γ-GTP, and high-sensitive CRP were decreased and adiponectin was increased only in miglitol group. CONCLUSIONS: Our results indicated that miglitol showed an anti-obesity potential, which was achieved by reducing abdominal fat accumulation and/or enhanced insulin requirement, and then corrected both the metabolic and hemodynamic aberrations seen in patients with the metabolic syndrome (UMIN Clinical Trial Registry UMIN000007650).
International journal of cardiology 06/2012; · 7.08 Impact Factor
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Nippon rinsho. Japanese journal of clinical medicine 05/2012; 70 Suppl 3:39-46.
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Nihon Naika Gakkai Zasshi 04/2012; 101(4):1027-33.
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Circulation Journal 02/2012; 76(3):593-5. · 3.77 Impact Factor
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Ken Yamakawa,
Michio Shimabukuro,
Namio Higa,
Tomohiro Asahi,
Kageyuki Ohba,
Osamu Arasaki,
Moritake Higa,
Yoshito Oshiro,
Hisashi Yoshida,
Tohru Higa,
Taro Saito,
Shinichiro Ueda, Hiroaki Masuzaki,
Masataka Sata
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ABSTRACT: We investigated the effects of purified eicosapentaenoic acid (EPA) on vascular endothelial function and free fatty acid composition in Japanese hyperlipidemic subjects. In subjects with hyperlipidemia (total cholesterol ≥220 mg/dL and/or triglycerides ≥150 mg/dL), lipid profile and forearm blood flow (FBF) during reactive hyperemia were determined before and 3 months after supplementation with 1800 mg/day EPA. Peak FBF during reactive hyperemia was lower in the hyperlipidemic group than the normolipidemic group. EPA supplementation did not change serum levels of total, HDL, or LDL cholesterol, apolipoproteins, remnant-like particle (RLP) cholesterol, RLP triglycerides, or malondialdehyde-modified LDL cholesterol. EPA supplementation did not change total free fatty acid levels in serum, but changed the fatty acid composition, with increased EPA and decreased linoleic acid, γ-linolenic acid, and dihomo-γ-linolenic acid. EPA supplementation recovered peak FBF after 3 months. Peak FBF recovery was correlated positively with EPA and EPA/arachidonic acid levels and correlated inversely with dihomo-γ-linolenic acid. EPA supplementation restores endothelium-dependent vasodilatation in hyperlipidemic patients despite having no effect on serum cholesterol and triglyceride patterns. These results suggest that EPA supplementation may improve vascular function at least partly via changes in fatty acid composition.
Cardiology research and practice. 01/2012; 2012:754181.
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ABSTRACT: The limitation of QRS duration as a surrogate measure for left ventricular (LV) mechanical dyssynchrony (LVMD) in cardiac resynchronization therapy (CRT) patient selection encourages seeking alternatives to QRS duration. Exploring the potential of an analysis program of electrocardiographically gated myocardial perfusion single photon emission computed tomography (SPECT) (GMPS) for the estimation of LVMD to predict CRT response.
Twenty-four patients undergoing CRT for advanced heart failure caused by non-ischaemic cardiomyopathy were studied. Gated myocardial perfusion single photon emission computed tomographies were performed in the setting of temporary CRT suspension after 1 week of CRT adoption. The GMPS data were computed with a novel program capable of segmental LV time-volume analysis. When a brain natriuretic peptide (BNP) value decreased >50% at 6-month follow-up, the patient was defined as a CRT responder. Receiver operating characteristic (ROC) curves for identification of responders were analysed for standard deviation of time to end systole (TES-SD) among 17 LV segments. Linear regression analyses demonstrated that an increase in percentage reduction in BNP level at 6-month follow-up was predicted by an increase in TES-SD (R(2) = 0.21, P = 0.023). The TES-SD in responders (n = 15, 62.5%) was higher than that in non-responders (100 ± 51 vs. 41 ± 17 ms, P = 0.0008). A cutoff value of TES-SD >49 ms predicted responders with 100% sensitivity and 78.8% specificity and the area under the ROC curve was 0.881 for TES-SD (P = 0.002).
The estimation of LVMD using this novel GMPS program could be an alternative or a complementary approach to QRS duration in CRT patient selection. This finding warrants further assessment of our approach in larger studies.
Europace 08/2011; 13(12):1731-7. · 1.98 Impact Factor
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ABSTRACT: Predictors of T wave oversensing with implantable cardioverter-defibrillator (ICD) systems remains to be clarified.
Thirteen consecutive patients who underwent ICD implantations were included. The depolarization (R) and repolarization (T) of bipolar electrograms during baseline, AAI and DDD modes, and an isoproterenol (ISO) infusion were evaluated. The R wave amplitude during DDD was significantly lower as compared to that during the other conditions in all high-pass filter settings. In contrast, there was no significant difference in the T wave amplitude during the DDD as compared to the other conditions. With the DDD, there was a significantly higher incidence of a T/R ratio of greater than 0.25 as compared to that with the other conditions. T wave amplitude in Brugada syndrome was significantly higher than that in non-Brugada syndrome. The existence of Brugada syndrome and T/R ratio during the AAI with a high-pass filter setting of 10/20 Hz was an excellent predictor of T wave oversensing in the follow-up period.
DDD had a significant impact on the R wave amplitude reduction and the T/R ratio during AAI can be predictors of T wave oversensing. These findings have important implications for inappropriate shocks due to T wave oversensing.
Circulation Journal 07/2011; 75(9):2095-104. · 3.77 Impact Factor
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Nihon Naika Gakkai Zasshi 04/2011; 100(4):983-8.
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ABSTRACT: Glucose intolerance is recognized as a predictor of congestive heart failure (CHF). However, the association of postprandial hyperglycemia or fasting hyperglycemia with CHF has not been clarified. We determined the impact of the total spectrum of glucose abnormalities on left ventricular (LV) geometry and diastolic function.
Two hundred and eighty-seven Japanese subjects who visited the university hospital to be checked for glucose intolerance or known type 2 diabetes were consecutively recruited. Participants underwent an oral glucose tolerance test if they had no history of diabetes, and LV geometry and LV systolic and diastolic function were analyzed by Doppler echocardiography.
The frequency of LV diastolic dysfunction in subjects with normal glucose tolerance, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), newly detected diabetes, and known diabetes were 13, 22, 50, 51, and 61%, respectively (χ(2) = 54.2, P < 0.0001). IGT was a predictor for LV diastolic dysfunction after adjusting for age, sex, systolic blood pressure, and heart rate (odds ratio 3.43 [95% CI 1.09-11.2]), but IFG was not (0.49 [0.06-3.08]). IGT was a predictor after adjusting for established CHF risk factors but was no longer significant after adjusting for BMI and homeostasis model assessment of insulin resistance.
In this hospital-based registry of subjects without CHF, the prevalence of LV diastolic dysfunction was higher in subjects with IGT but not in those with IFG. Results suggest that IGT, as well as newly detected and known diabetes, could be linked to an increased risk of cardiovascular events, partly through LV diastolic dysfunction.
Diabetes care 02/2011; 34(3):686-90. · 8.09 Impact Factor
