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Dive into the research topics where Toru Funahashi is active.

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Featured researches published by Toru Funahashi.


International Journal of Obesity | 1997

Two decades of annual medical examinations in Japanese obese children : do obese children grow into obese adults?

Kazuaki Kotani; Makoto Nishida; Shizuya Yamashita; Toru Funahashi; Fujioka S; Katsuto Tokunaga; K Ishikawa; Tarui S; Yuji Matsuzawa

OBJECTIVE: To investigate trends in frequency of obese children in Japan over two decades, the frequency of obese children who grow into obese adults and predictive factors for adult obesity. DESIGN: Annual cross-sectional studies for 22 y (1974–1995) with a follow-up study. SUBJECTS: Cross-sectional: Cumulatively 13 186 obese (% of standard body weight (SBW): ≥120%) schoolchildren including 3158 extremely obese (≥140% of SBW) children out of 203 088 schoolchildren (age: 6–14 y) in Izumiohtsu City, Osaka, Japan. Follow-up: 151 initially obese children (initial age: 6–14 y and age at follow-up: 20–35 y) who lived in Izumiohtsu City. Control: 3552 Japanese men and 4631 Japanese women (age: 20–35 y). MEASUREMENTS: Cross-sectional: height, weight, trunk circumference, skin-fold thickness, blood pressure and blood biochemicals. Follow-up: height, weight, trunk circumference, skin-fold thickness during childhood, and body height and weight at follow-up. Adulthood obesity: ≥120% of the average body mass indices (BMI) of the controls. RESULTS: Frequency of obese children increased from 5% to more than 10%, and that of extremely obese children increased from 1% to more than 2% during these 22 y. These increases were most prominent in the schoolboys aged 9–11 y. Prevalence of hyperglycemia and hyperlipidemia in the extremely obese children did not change, and that of hypertension and abnormal liver function gradually decreased during these two decades. After coming of age, 32.2% of the initially obese boys (relative risk: 5.3) and 41.0% of the initially obese girls (relative risk: 6.7) remained obese. BMI, percentage of the SBW and skin-fold thickness at the biceps during childhood were significantly larger in currently-obese girls. Positive correlations were demonstrated between these variables and percentage SBW at follow-up. CONCLUSIONS: Childhood obesity is increasing in Japan, especially in boys aged 9–11 y. Approximately 32% of the obese boys and 41% of the obese girls grow into obese adults, and the degree of obesity is a predictive factor for adult obesity.


Experimental Biology and Medicine | 2007

Effects of Adiponectin on the Renal Sympathetic Nerve Activity and Blood Pressure in Rats

Mamoru Tanida; Jiao Shen; Yuko Horii; Morihiro Matsuda; Shinji Kihara; Toru Funahashi; Iichiro Shimomura; Hajime Sawai; Yutaka Fukuda; Yuji Matsuzawa; Katsuya Nagai

Adiponectin is an adipocytokine that modulates energy homeostasis and glucose metabolism. Here, we examined the effects of acute intravenous (iv) and lateral cerebral ventricular (LCV) injections of adiponectin on the renal sympathetic nerve activity (RSNA) and blood pressure (b/p) in urethane-anesthetized rats. Both iv and LCV injections of adiponectin induced dose-dependent suppressions of RSNA and b/p. Moreover, we found that bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) abolished the effects of iv injection of adiponectin on RSNA and b/p. These findings suggest that adiponectin decreases the RSNA and b/p in a dose-dependent manner and that the SCN is implicated in mechanism of adiponectin actions on RSNA and b/p. These findings also suggest that the hypotensive-action activity of adiponectin is realized, at least partially, via changes in activities of autonomic nerves activity.


European Journal of Clinical Investigation | 1995

Decreased affinity of low density lipoprotein (LDL) particles for LDL receptors in patients with cholesteryl ester transfer protein deficiency

Naohiko Sakai; Shizuya Yamashita; Ken-ichi Hirano; Masato Ishigami; Takeshi Arai; K. Kobayashi; Toru Funahashi; Yuji Matsuzawa

Abstract. We have reported that the disorder of lipoprotein metabolism in hyperalphalipoproteinae‐mic patients with a deficiency of cholesteryl ester transfer protein (CETP) is characterized by the poly‐disperse low density lipoprotein (LDL) particles and the accumulation of cholesteryl ester (CE) in high density lipoprotein (HDL) particles, forming cholesterol‐induced HDL (HDLc)‐like particles. In the present study we have investigated the interaction of these abnormal LDL with LDL receptors of normal human fibroblasts. Since the ultracentrifugally separated LDL fraction (1.019 < d < 1.063 gmL‐1) from the CETP‐deficient patients contained HDLc‐like particles, these particles were removed by anti‐apolipoprotein (apo) A‐I immunoaffinity column chromatography. The lipoproteins eluted in the unbound fraction of this column did not contain apo A‐I, so this fraction was considered to be authentic LDL. The authentic LDL of the patients were deficient in CE and rich in triglycerides and apo B. The authentic LDL itself showed polydispersity, ranging in size from 23 nm to 30 nm. The affinity of these abnormal LDL particles for LDL receptors was analysed by a competitive assay in which cold LDL from the patients or control compete with 125I‐labelled LDL for fibroblast LDL receptors. The concentration of LDL particles at which 50% of 125I‐labelled normal LDL was replaced was two to three times higher for the patients than for the normal control. Therefore, the affinity of patient LDL was thought to be reduced compared to that of control LDL. These results demonstrate that CETP may play an important role in making LDL particles homogeneous and rich in CE. This modulation of LDL by CETP may enhance the affinity of LDL for LDL receptors to deliver cholesterol to peripheral tissues.


International Journal of Obesity | 1997

Importance of intra-abdominal visceral fat accumulation to coronary atherosclerosis in heterozygous familial hypercholesterolaemia

Toshikazu Nakamura; H Kobayashi; K Yanagi; Tsutomu Nakagawa; Makoto Nishida; Shinji Kihara; H Hiraoka; Shuichi Nozaki; Toru Funahashi; Shizuya Yamashita; Kaoru Kameda-Takemura; Yuji Matsuzawa

OBJECTIVES: Hyper-low-density lipoprotein (LDL)-cholesterolaemia is a potent risk factor for coronary atherosclerosis. We have recently demonstrated that a cluster of risk factors including insulin resistance, glucose intolerance, hypertriglyceridaemia, and hypertension based on intra-abdominal visceral fat accumulation are closely related to coronary artery disease. In the current study, we evaluated the relationship between visceral fat accumulation and the severity and distribution of coronary atherosclerosis in familial hypercholesterolaemia (FH). DESIGN: The effect of visceral fat accumulation on coronary lesions and risk factors in patients with FH was investigated. SUBJECTS: Thirty-one male patients with heterozygous FH who underwent coronary angiography. MEASUREMENTS: Abdominal fat distribution was estimated by a cross-sectional computed tomographic scan at the umbilical level. Plasma lipid, glucose and insulin concentrations and blood pressure were measured. A 75 g oral glucose tolerance test was also performed. RESULTS: The patients were divided into two groups according to the degree of visceral fat accumulation. Fifteen patients had high visceral fat accumulation (High VF group) and 16 patients had normal visceral fat accumulation (Normal VF group). Body mass index (BMI) and subcutaneous fat area were significantly higher in the high VF group. Baseline serum triglyceride was significantly higher and baseline low-density lipoprotein (LDL)-cholesterol and reduction of LDL-cholesterol during treatment were significantly lower in High VF group. Fasting plasma glucose and insulin concentrations, and systolic and diastolic pressures were significantly higher in the High VF group. Significant correlations were found between visceral fat area and the sum of the glucose and insulin concentration during an oral glucose tolerance test. Visceral fat area was significantly correlated with the severity of coronary stenosis index. Distal coronary lesions were significantly more frequent in the High VF group. moreover, the correlation between the visceral fat area and coronary stenosis index was found to be independent of age, BMI, and subcutaneous fat area by multiple regression analysis. CONCLUSIONS: Visceral fat accumulation is a potent cardiovascular risk factor in heterozygous FH.


The Lancet | 1990

Hypocholesterolaemic factor from gallbladder cancer cells

Yuya Ueyama; Yuji Matsuzawa; Shizuya Yamashita; Toru Funahashi; Naohiko Sakai; Toshikazu Nakamura; Masaharu Kubo; Seiichiro Tarui

A patient is reported with drug-resistant familial hypercholesterolaemia in whom serum cholesterol fell after the onset of gallbladder cancer with intraperitoneal invasion. Cancer cells were obtained from ascitic fluid and a cultured cell line established. Incubation of the culture medium of these cells with skin fibroblasts from the patient and from normal subjects increased low-density lipoprotein (LDL) receptor activity in a dose-dependent manner. These results show that gallbladder cancer cells from this patient secrete a substance that stimulates LDL receptor activity. This substance may have contributed towards reduction of serum cholesterol.


Hypertension Research | 2012

Plasma adiponectin levels predict cardiovascular events in the observational Arita Cohort Study in Japan: the importance of the plasma adiponectin levels.

Chun-Yen Chen; Masanori Asakura; Hiroshi Asanuma; Takuya Hasegawa; Jun Tanaka; Norihisa Toh; Kyung Duk Min; Hideaki Kanzaki; Hiroyuki Takahama; Makoto Amaki; Yumi Itoh; Go Ichien; Yoko Okumoto; Toru Funahashi; Jiyoong Kim; Masafumi Kitakaze

As the plasma level of adiponectin is related to metabolic syndrome and cardiovascular events, a low plasma adiponectin level may either cause or trigger cardiovascular disorders. The purpose of this study was to determine whether a low adiponectin level contributes to cardiovascular events, and to investigate the factors influencing adiponectin in the Japanese Arita-cho cohort study.We followed about 2000 subjects in Arita-cho, Saga, Japan as a cohort study, and we enrolled 637 subjects (205 men; 65.1±8.3 years old) who participated in annual health checks from 2005 to 2008 and underwent measurement of the plasma adiponectin level and an oral glucose tolerance test. We monitored the incidence of cardiovascular or cerebrovascular events in these subjects until the end of 2010, discontinuing follow-up at 3 years after the start of enrollment. Subjects with low plasma adiponectin levels (<10.5 ng ml−1) had a higher incidence of newly diagnosed cardiovascular diseases such as acute heart failure or acute myocardial infarction than those with high plasma adiponectin levels (⩾10.5 ng ml−1) over an average of 2.95 years of follow-up. Multivariate analysis showed that the adiponectin level was predicted by the following parameters in all subjects: age (β=0.16), male gender (β=−0.267), homeostasis model assessment of insulin resistance (β=−0.140) and the plasma levels of high-density lipoprotein cholesterol (β=0.104), uric acid (β=−0.13), triglycerides (β=−0.169) and brain natriuretic peptide (β=0.151). The difference in plasma glucose before and 120 min after the intake of a 75-g glucose load did not influence the plasma adiponectin level. The plasma adiponectin level is useful for predicting cardiovascular events, and is a measure of the risk of lifestyle-related diseases.


Circulation | 2000

Tangier Disease With Continuous Massive and Longitudinal Diffuse Calcification in the Coronary Arteries Demonstration by the Sagittal Images of Intravascular Ultrasonography

Ryutaro Komuro; Shizuya Yamashita; Satoru Sumitsuji; Ken-ichi Hirano; Takao Maruyama; Makoto Nishida; Fumihiko Matsuura; Akifumi Matsuyama; Taizo Sugimoto; Noriyuki Ouchi; Naohiko Sakai; Tadashi Nakamura; Toru Funahashi; Yuji Matsuzawa

A 48-year-old man was first referred to our clinic in January 1989 because of marked hypocholesterolemia with very low HDL cholesterol, anemia, and hyperbilirubinemia. He had large tonsils, corneal opacities, hepatosplenomegaly, and thrombocytopenia. Serum levels of total cholesterol, triglycerides, and HDL cholesterol were 0.72, 2.6, and 0.16 mmol/L (28, 232, and 6 mg/dL), respectively. Concentrations of apolipoproteins (apo) A-I and A-II were 1.3 and 0.9 μmol/L (3.9 and 1.5 mg/dL), respectively. His daughter’s serum levels of total cholesterol, HDL cholesterol, and apo A-I were 3.3 mmol/L, 0.64 mmol/L, and 34.7 μmol/L (128, 24, and 104 mg/dL), respectively. He was diagnosed with Tangier disease by clinical manifestations, analysis of lipoproteins, and 2D electrophoresis, which confirmed the increase of preproapo A-I. Interestingly, xanthoma in the Achilles’ tendons, which had rarely been reported in patients with Tangier disease, was observed in the patient, and the thickness was 9 mm (mean of bilateral determinations; control, 6±2 mm). Subsequently, …


American Journal of Respiratory Cell and Molecular Biology | 2013

Validation of Noninvasive Morphological and Diffusion Imaging in Mouse Emphysema by Micro–Computed Tomography and Hyperpolarized 129Xe Magnetic Resonance Imaging

Satoshi Tetsumoto; Yoshito Takeda; Hirohiko Imai; Atsuomi Kimura; Yingji Jin; Kaori Nakanishi; Yohei Maeda; Hanako Kuhara; Kazuyuki Tsujino; Takeo Iwasaki; Hiroshi Shigeta; Yasushi Kondo; Mari Ito; Toshiyuki Minami; Haruhiko Hirata; Ryo Takahashi; Satoshi Kohmo; Izumi Nagatomo; Koji Inoue; Hiroshi Kida; Takashi Kijima; Isao Tachibana; Norikazu Maeda; Toru Funahashi; Iichiro Shimomura; Hideaki Fujiwara; Atsushi Kumanogoh

Animal disease models are pivotal in investigating the pathogenesis of emphysema and developing novel drugs, but the modalities to evaluate murine emphysema models have been of limited validity and sensitivity. In this study, we evaluated hyperpolarized (129)Xe magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) compared with 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 according to the mean linear intercept and plethysmography parameters. Notably, the distribution of low-density areas, as 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 (129)Xe MRI, which can evaluate gas exchange between the 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 of the fD value in low-density areas with 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 (129)Xe MRI and micro-CT in combination with traditional modalities. These noninvasive modalities provide complementary data that can be used for repeated estimations of regional gas exchange and lung morphology.


Journal of Internal Medicine | 1996

A compound heterozygote for familial hypercholesterolaemia with a homozygous mother

Toru Funahashi; Shizuya Yamashita; Takao Maruyama; Yuya Ueyama; M. Menju; Yoshiyuki Nagai; Kaoru Takemura; Y. Miyake; Shoji Tajima; Yuji Matsuzawa

Homozygous familial hypercholesterolaemia (FH) is a rare disorder in which the patients develop severe hypercholesterolaemia and premature coronary atherosclerosis from childhood. Here we report a unique family with clustering of homozygous FH. The proband was a 25‐year‐old man, who showed marked hypercholesterolaemia, multiple xanthomas and severe coronary atherosclerosis. His mother also showed the typical characteristics of homozygous FH. Sequencing analysis of the low‐density lipoprotein receptor gene revealed that he was a compound heterozygote, carrying two different point mutations. One was a novel mutation, FH Wakayama (Cys→A Ser at 317), derived from his mother, and the other was a recurrent mutation, FH Niigata (T→A C at 1845+2, 5′ splice signal in intron 12), derived from his father. The proband we report seems to be a very rare case of an FH homozygote born from a homozygous mother.


Biochemical and Biophysical Research Communications | 1995

Enhanced Expression of Rat Obese (ob) Gene in Adipose Tissues of Ventromedial Hypothalamus-Lesioned Rats

Toru Funahashi; Iichiro Shimomura; Hisatoyo Hiraoka; Toru Arai; Motoko Takahashi; Tosikazu Nakamura; Shuichi Nozaki; Shizuya Yamashita; Kaoru Takemura; Katsuto Tokunaga; Yuji Matsuzawa

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