Faculty Profiles - SONE, Hirohito

[Intervention study for elevating high density lipoprotein cholesterol level]. Reviewed

Kodama S, Sone H

Nihon rinsho. Japanese journal of clinical medicine 65 Suppl 7 264 - 269 2007.7

Protein kinase A suppresses sterol regulatory element-binding protein-1C expression via phosphorylation of liver X receptor in the liver Reviewed

Takashi Yamamoto, Hitoshi Shimano, Noriyuki Inoue, Yoshimi Nakagawa, Takashi Matsuzaka, Akimitsu Takahashi, Naoya Yahagi, Hirohito Sone, Hiroaki Suzuki, Hideo Toyoshima, Nobuhiro Yamada

JOURNAL OF BIOLOGICAL CHEMISTRY 282 ( 16 ) 11687 - 11695 2007.4

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Sterol regulatory element-binding protein ( SREBP)-1c is a transcription factor that controls synthesis of fatty acids and triglycerides in the liver and is highly regulated by nutrition and hormones. In the current studies we show that protein kinase A ( PKA), a mediator of glucagon/cAMP, a fasting signaling, suppresses SREBP-1c by modulating the activity of liver X receptor alpha( LXR alpha), a dominant activator of SREBP-1c expression. Activation of PKA repressed LXR-induced SREBP-1c expression both in rat primary hepatocytes and mouse livers. Promoter analyses revealed that the LXR alpha-binding site in the SREBP-1c promoter is responsible for PKA inhibitory effect on SREBP-1c transcription. In vitro and in vivo PKA directly phosphorylated LXR alpha, and the two consensus PKA target sites ( 195, 196 serines and 290, 291 serines) in its ligand binding/heterodimerization domain were crucial for the inhibition of LXR signaling. PKA phosphorylation of LXR alpha caused impaired DNA binding activity by preventing LXR alpha/RXR dimerization and decreased its transcription activity by inhibiting recruitment of coactivator SCR-1 and enhancing recruitment of corepressor NcoR1. These results indicate that LXR alpha is regulated not only by oxysterol derivatives but also by PKA-mediated phosphorylation, which suggests that nutritional regulation of SREBP-1c and lipogenesis could be regulated at least partially through modulation of LXR.

DOI： 10.1074/jbc.M611911200

Effect of exercise training on serum high-sensitivity C-reactive protein concentration in healthy middle-aged and elderly subjects

Ryuichi Ajisaka, Takumi Tanabe, Takeshi Otsuki, Haruka Murakami, Seiji Maeda, Kiyoji Tanaka, Hirohito Sone, Shinya Kuno

JAPANESE JOURNAL OF PHYSICAL FITNESS AND SPORTS MEDICINE 56 ( 1 ) 179 - 189 2007.2

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：JAPANESE SOC PHYSICAL FITNESS SPORTS MEDICINE

High-sensitivity C-reactive protein (CRP) is a novel risk factor for coronary artery disease. It is well known that body weight loss is effective in reducing serum CRP concentration : however, the effect of exercise training on serum CRP concentration has not been fully elucidated. The purpose of this study was to examine the effect of a 24-week exercise training program on serum CRP concentration in 169 healthy middle-aged and elderly subjects (65.9 +/- 6.4 years) Each subject Underwent baseline testing (peak oxygen Uptake, daily physical activity, body weight, and serum CRP levels), and repeated these tests on completion of the training program. The subjects were classified into 2 groups based on initial CRP levels : normal < 1.0 mg/L, n=139, and high >= 1.0 mg/L, n = 30. On completion of the program, both daily physical activity and peak oxygen uptake increased significantly (+33.9 +/- 72.4%, p < 0.0001, +5.4 +/- 14.7%, p= 0.014, respectively). However, body weight did not change significantly. In addition, CRP levels of the entire group did not change significantly. However, CRP levels significantly decreased among the high baseline CRP group (from 1.82 +/- 0.81 mg/L to 0.98 +/- 0.59 mg/L, p < 0.0001). it was concluded that serum CRP levels are reduced without body weight loss in response to exercise training in healthy middle-aged and elderly subjects with high initial CRP levels.

[Long-term intervention studies of diabetic macroangiopathy in Japan and western countries]. Reviewed

[Metabolic syndrome in Japanese patient with diabetes analysis from JDCS]. Reviewed

Sone H, Akanuma Y, Yamada N

Nihon rinsho. Japanese journal of clinical medicine 64 Suppl 9 74 - 83 2006.12

Sone H, Yamada N

Nihon rinsho. Japanese journal of clinical medicine 64 ( 11 ) 2021 - 2030 2006.11

Aldo-keto reductase 1 family B7 is the gene induced in response to oxidative stress in the livers of Long-Evans Cinnamon rats

Guang Jia, Ryoya Takahashi, Zhiping Zhang, Yoshiaki Tsuji, Hideko Sone

International Journal of Oncology 29 ( 4 ) 829 - 838 2006.10

Language：English Publishing type：Research paper (scientific journal) Publisher：Spandidos Publications

The Long-Evans Cinnamon (LEC) rat strain (Atp7b m/m), which accumulates copper in the liver due to mutations in the Atp7b gene, is a useful model for investigating the relationship between oxidative stress and hepatocarcinogenesis. To determine the effect of this mutation on oxidative stress marker genes, we performed oligonucleotide array analysis (Affymetrix), and compared the results in Atp7b m/m rats with those of a sibling line with the Atp7b w/w genotype. We focused our studies on the expression of the aldo-keto reductase 1 family B7 (AKR1B7)-like protein gene, since this gene codes for reductase enzymes involved in the detoxification of oxidizing compounds (e.g., aldehydes) and was differentially expressed in Atp7b m/m and Atp7b w/w rat liver. Akr1B7 mRNA expression was significantly increased in comparison with the expression of 4 other known oxidative stress responsive genes, haem-oxygenase-1 (HO-1), thioredoxin (Trx), aldehyde reductase (AKR1A1), and glucose-6-phosphate dehydrogenase (G6PDH). By searching binding motifs, five nuclear factor kappa B (NF-κB) binding sites were located in the 5′-upstream region of the Akr1b7 gene. Transient co-transfection with both I-κBα and the Akr1b7 6 kb promoter (p6.0-AKR-Luc) inhibited luciferase activity of p6.0-AKR-Luc in HepG2 cells. Cuprous ion however did not affect the transcription activity induced by p6.0-AKR-Luc. Gel-shift assay showed that the DNA binding activity of NF-κB increased in the livers of LEC rats, suggesting that the oxidative stress is mediated through NF-κB. The results indicate conclusively that in LEC rat liver, Akr1b7 might be up-regulated by oxidative stress mediated through NF-κB, but not that mediated directly by copper.

DOI： 10.3892/ijo.29.4.829

Scopus

Distribution of retinylester-storing stellate cells in the arrowtooth halibut, Atheresthes evermanni

Kiwamu Yoshikawa, Katsuyuki Imai, Takaharu Seki, Nobuyo Higashi-Kuwata, Naosuke Kojima, Mitsuharu Yuuda, Kazuo Koyasu, Hiroshi Sone, Mitsuru Sato, Haruki Senoo, Toshiaki Irie

Comparative Biochemistry and Physiology - A Molecular and Integrative Physiology 145 ( 2 ) 280 - 286 2006.10

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier Inc.

Hepatic stellate cells play a major role in retinylester storage in mammals, but the retinoid-storing state in nonmammalian vertebrates remains to be elucidated. In this study, we examined retinoids and retinoid-storing cells in the arrowtooth halibut, Atheresthes evermanni. High-performance liquid chromatography analyses revealed the highest concentrations of stored retinoids (retinol and retinylester, 6199 nmol/g) in the pyloric cecum, a teleost-specific organ protruding from the intestine adjacent to the pylorus. Considerable amounts of retinoids were also stored in the intestine (3355 nmol/g) and liver (1891 nmol/g), and small amounts in the kidney (102 nmol/g). Very small amounts or no retinoids were detected in the heart, gill, skeletal muscle, and gonads (less than 2 nmol/g). Use of gold chloride staining and fluorescence microscopy to detect retinoid autofluorescence showed that, in the pyloric cecum and intestine, retinoid-storing cells were localized in the lamina propria mucosae. Under electron microscopy, cells containing well-developed lipid droplets, which are common morphological characteristics of the hepatic stellate cells of mammals, were observed in the lamina propria mucosae of the pyloric cecum. Thus, the distribution of stellate cells with retinoid-storing capacity differs between this halibut and mammals, suggesting that the retinoid-storing site has shifted during vertebrate evolution. © 2006 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cbpa.2006.06.043

Scopus

Leptin resistance conferred by a combination of single nucleotide polymorphism and the adoption of a western lifestyle in urban areas of Thailand

Hirohito Sone

The Journal of Nutrition, Health & Aging 2006

Leptin resistance conferred by a combination of single nucleotide polymorphism and the adoption of a Western lifestyle in urban areas of Thailand.

Yanagisawa Y, Iwamoto S, Kawabata T, Nakamura Y, Charupoonphol P, Supannatas S, Sone H, Kaneko Y, Watanabe S, Komatsu F, Sakuma M, Miyagi S, Hasegawa K, Kagawa Y

2006

Exercise Training for Ameliorating Cardiovascular Risk Factors-focusing on Exercise Intensity and Amount

Kodama Satoru, Miao Shu, Yamada Nobuhiro, Sone Hirohito

Int. J. Sport Health Sci. 4 325 - 338 2006

Language：English Publisher：Japan Society of Physical Education, Health and Sport Sciences

Exercise training suppresses cardiovascular risk factors by improving lipid/glucose metabolism, insulin resistance and hypertension. There is an optimum amount and intensity of exercise that will suppress each risk factor, although limited information is currently available on this area. For instance, the level of high-density lipoprotein cholesterol seems to be dependent more on the amount than on the intensity of exercise training; the situation with exercise-induced suppression of triglyceride levels is less clear. It is notable that the ability of mild intensity or a low amount of exercise to suppress or prevent cardiovascular risk factors is largely unknown. This knowledge is essential for prescribing safe and effective exercise training to elderly people. At the same time, very few studies on the associations between cardiovascular risk factors in response to exercise can be found. For example, improvement in lipid metabolism or insulin resistance seems to be related to the weight loss seen during exercise training but weight-independent effects could also be observed. The optimal intensity and amount of exercise training for each cardiovascular risk factor and the relationships between the effects of exercise training on each risk factor need to be clarified in the near future in order to establish guidelines that can be applied to the majority of elderly people at risk of cardiovascular diseases.

DOI： 10.5432/ijshs.4.325

CiNii Article

Other Link： http://search.jamas.or.jp/link/ui/2007328852

Sterol regulatory element-binding proteins activate insulin gene promoter directly and indirectly through synergy with BETA2/E47 Reviewed

M Amemiya-Kudo, J Oka, T Ide, T Matsuzaka, H Sone, T Yoshikawa, N Yahagi, S Ishibashi, J Osuga, N Yamada, T Murase, H Shimano

JOURNAL OF BIOLOGICAL CHEMISTRY 280 ( 41 ) 34577 - 34589 2005.10

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Insulin gene expression is regulated by pancreatic beta cell-specific factors, PDX-1 and BETA2/E47. Here we have demonstrated that the insulin promoter is a novel target for SREBPs established as lipid-synthetic transcription factors. Promoter analyses of rat insulin I gene in non-beta cells revealed that nuclear SREBP-1c activates the insulin promoter through three novel SREBP-binding sites (SREs), two of which overlap with E-boxes, binding sites for BETA2/ E47. SREBP-1c activation of the insulin promoter was markedly enhanced by co-expression of BETA2/ E47. This synergistic activation by SREBP-1c/ BETA2/ E47 was not mediated through SREs but through the E-boxes on which BETA2/ E47 physically interacts with SREBP-1c, suggesting a novel function of SREBP as a co-activator. These two cis-DNA regions, E1 and E2, with an appropriate distance separating them, were mandatory for the synergism, which implicates formation of SREBP-1c center dot BETA2 center dot E47 complex in a DNA looping structure for efficient recruitment of CREB- binding protein/ p300. However, in the presence of PDX1, the synergistic action of SREBP-1c with BETA2/E47 was canceled. SREBP-1c-mediated activation of the insulin promoter and expression became overt in beta cell lines and isolated islets when endogenous PDX-1 expression was low. This cryptic SREBP-1c action might play a compensatory role in insulin expression in diabetes with beta cell lipotoxicity.

DOI： 10.1074/jbc.M506718200

Effects of aerobic training on visceral fat and glucose metabolism in older adults

Y Hayashi, K Tanaka, H Sone, S Kuno

JAPANESE JOURNAL OF PHYSICAL FITNESS AND SPORTS MEDICINE 54 ( 4 ) 305 - 313 2005.8

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：JAPANESE SOC PHYSICAL FITNESS SPORTS MEDICINE

Excess accumulation of visceral fat is reported to promote insulin resistance. However, it is not known whether or not insulin resistance improves without reducing visceral fat. Recent studies have reported, however, that exercise can improve insulin resistance. The aim of this study was to examine the effects of low-intensity exercise training on insulin resistance and visceral fat. Participants were 26 older adults, aged 63.9 +/- 3.9 years, who were divided into two groups based on visceral fat area (VFA, cm(2)) measured by X-ray computed tomography. Eight men (153.4 +/- 49.4 cm(2)) and 5 women (151.9 +/- 45.5 cm(2)) were classified as having a VFA of 100 cm(2) or more (VFO group), and 6 men and 6 women as having less than 100 cm(2) (C group). After a 14-week exercise training program, VFA in women of the VFO group was significantly reduced (126.3 +/- 40.0 cm(2)); though it did not reach 100 cm(2). However, homeostasis model assessment (HOMA-IR), an index of insulin resistance, significantly improved from 4.6 +/- 1.9 to 2.2 +/- 1.1 among women in the VFO group. These data suggest that improvements in insulin resistance for women with relatively high VFA are weakly associated with exercise-induced reductions in VFA. Based on these results, the activation of skeletal muscle with physical activity has the possibility of being independently associated with an improvement in insulin resistance without a significant decrease of VFA.

Transgenic mice overexpressing SREBP-1a under the control of the PEPCK promoter exhibit insulin resistance, but not diabetes. International journal

Akimitsu Takahashi, Hitoshi Shimano, Yoshimi Nakagawa, Takashi Yamamoto, Kaori Motomura, Takashi Matsuzaka, Hirohito Sone, Hiroaki Suzuki, Hideo Toyoshima, Nobuhiro Yamada

Biochimica et biophysica acta 1740 ( 3 ) 427 - 33 2005.6

Language：English Publishing type：Research paper (scientific journal)

Sterol regulatory element-binding protein-1 (SREBP-1) is a transcription factor which regulates genes involved in the synthesis of fatty acids and triglycerides. The overexpression of nuclear SREBP-1a in transgenic mice under the control of the PEPCK promoter (TgSREBP-1a) caused a massively enlarged fatty liver and disappearance of peripheral white adipose tissue. In the current study, we estimated the impact of this lipid transcription factor on plasma glucose/insulin metabolism in vivo. TgSREBP-1a exhibited mild peripheral insulin resistance as evidenced by hyperinsulinemia both at fasting and after intravenous glucose loading, and retarded glucose reduction after insulin injection due to decreased plasma leptin levels. Intriguingly, hyperinsulinemia in TgSREBP-1a mice was markedly exacerbated in a fed state and sustained after intravenous glucose loading, and paradoxically decreased after the portal injection of glucose. TgSREBP-1a mice consistently showed very small plasma glucose increases after portal glucose loading because of a large capacity for hepatic glucose uptake. These data suggested that hepatic insulin resistance emerges postprandially. In addition, pancreatic islets from TgSREBP-1a were enlarged. These data demonstrate that SREBP-1a activation in the liver has a strong impact on plasma insulin levels, implicating the potential role of SREBPs in hepatic insulin metabolism relating to insulin resistance.