Details of a Researcher - WADA Nobuhiro

Papers - WADA Nobuhiro

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Associations of sleep quality with the skeletal muscle strength in patients with type 2 diabetes with poor glycemic control.

Takanori Hayashi, Nobuhiro Wada, Tetsuya Kubota, Chie Koizumi, Yoshitaka Sakurai, Masakazu Aihara, Satoshi Usami, Toshimasa Yamauchi, Naoto Kubota

Journal of diabetes investigation 14 ( 6 ) 801 - 810 2023.06 [Domestic journal]

AIMS/INTRODUCTION: Patients with type 2 diabetes mellitus are reported to be at a high risk for sarcopenia, and are known to have a poorer sleep quality. However, the association between sleep quality and skeletal muscle in patients with type 2 diabetes mellitus is not yet precisely understood. MATERIALS AND METHODS: A total of 110 inpatients with type 2 diabetes mellitus aged 40-90 years were enrolled. The sleep quality was assessed using the Pittsburgh sleep quality index (PSQI). Skeletal muscle mass was measured using bioelectrical impedance analysis. Muscle strength was evaluated by measuring the grip strength. We also performed dietary surveys and measurements of the plasma amino acid levels. RESULTS: A high total score on the PSQI was significantly associated with reduced muscle strength, and the association persisted even after adjustments for confounders. On the other hand, adjusted analysis did not reveal any significant associations between the PSQI total score and the skeletal muscle mass. In regard to the associations with subscores of the PSQI, the scores for sleep latency, sleep efficiency, and daytime dysfunction were significantly negatively associated with the muscle strength. Although poor sleep quality was associated with a high confectionery intake and low plasma arginine, citrulline, and ornithine levels, neither confectionery intake levels nor the plasma levels of these amino acids was associated with the muscle strength. CONCLUSIONS: Our study revealed a significant association between the sleep quality and muscle strength in patients with type 2 diabetes mellitus. These results suggest that poor sleep quality is an important risk factor for sarcopenia in patients with type 2 diabetes mellitus.

DOI PubMed

Excessive folic acid supplementation in pregnant mice impairs insulin secretion and induces the expression of genes associated with fatty liver in their offspring

Yuri Kintaka, Nobuhiro Wada, Seiji Shioda, Sadako Nakamura, Yuko Yamazaki, Kazuki Mochizuki

Heliyon ( Elsevier {BV} ) 6 ( 4 ) 2020.04

DOI

Effect of Intranasal Administration of Galanin-like Peptide (GALP) on Body Weight and Hepatic Lipids Accumulation in Mice with Diet-induced Obesity

Satoshi Hirako, Nobuhiro Wada, Haruaki Kageyama, Fumiko Takenoya, Hyounju Kim, Yuzuru Iizuka, Akiyo Matsumoto, Mai Okabe, Seiji Shioda

Current Pharmaceutical Design ( Bentham Science Publishers Ltd. ) 23 ( 25 ) 2017.09

DOI

Behavioral and omics analyses study on potential involvement of dipeptide balenine through supplementation in diet of senescence-accelerated mouse prone 8

Nobuhiro Wada, Satoru Yamanaka, Junko Shibato, R, eep Rakwal, Satoshi Hirako, Yuzuru Iizuka, Hyounju Kim, Akiyo Matsumoto, Ai Kimura, Fumiko Takenoya, Genta Yasunaga, Seiji Shioda

Genomics Data ( Elsevier {BV} ) 10 38 - 50 2016.12

Authorship： Lead author

This study investigates effects of dipeptide balenine, as a major component of whale meat extract (hereafter, WME), supplementation on senescence-accelerated mouse prone 8 (SAMP8), an Alzheimer's disease (AD) model at level of learning and memory formation and brain expression profiles genome-wide in brain. Mice fed experimental balenine (+ WME) supplemented diet for 26 weeks were subjected to four behavioral tests – open field, Y-maze, novel object recognition, and water-filled multiple T-maze – to examine effects on learning and memory. Brain transcriptome of SAMP8 mice-fed the WME diet over control low-safflower oil (LSO) diet-fed mice was delineated on a 4 × 44 K mouse whole genome DNA microarray chip. Results revealed the WME diet not only induced improvements in the learning and memory formation but also positively modulated changes in the brain of the SAMP8 mouse; the gene inventories are publically available for analysis by the scientific community. Interestingly, the SAMP8 mouse model presented many genetic characteristics of AD, and numerous novel molecules (Slc2a5, Treh, Fbp1, Aldob, Ppp1r1a, DNase1, Agxt2l1, Cyp2e1, Acsm1, Acsm2, and Pah) were revealed over the SAMR1 (senescence-accelerated mouse resistant 1) mouse, to be oppositely regulated/recovered under the balenine (+ WME) supplemented diet regime by DNA microarray and bioinformatics analyses. Our present study demonstrates an experimental strategy to understand the effects of dipeptide balenine, prominetly contained in meat diet, on SAMP8, providing new insight into whole brain transcriptome changes genome-wide. The gene expression data has been deposited into the Gene Expression Omnibus (GEO): GSE76459. The data will be a valuable resource in examining the effects of natural products, and which could also serve as a human model for further functional analysis and investigation.

DOI CiNii

Anti-obesity effect of intranasal administration of galanin-like peptide (GALP) in obese mice

Haruaki Kageyama, Kanako Shiba, Satoshi Hirako, Nobuhiro Wada, Satoru Yamanaka, Yukinori Nogi, Fumiko Takenoya, Naoko Nonaka, Tsutomu Hirano, Shuji Inoue, Seiji Shioda

Scientific Reports ( Springer Science and Business Media {LLC} ) 6 ( 1 ) 2016.09

DOI

Autonomic nervous system-mediated effects of galanin-like peptide on lipid metabolism in liver and adipose tissue

Satoshi Hirako, Nobuhiro Wada, Haruaki Kageyama, Fumiko Takenoya, Yoshihiko Izumida, Hyounju Kim, Yuzuru Iizuka, Akiyo Matsumoto, Mai Okabe, Ai Kimura, Mamiko Suzuki, Satoru Yamanaka, Seiji Shioda

Scientific Reports ( Springer Science and Business Media {LLC} ) 6 ( 1 ) 2016.08

DOI

Effect of Intracerebroventricular Administration of Galanin-Like Peptide on Hepatokines in C57BL/6 J Mice.

Satoshi Hirako, Nobuhiro Wada, Yuzuru Iizuka, Takahiro Hirabayashi, Haruaki Kageyama, Hyounju Kim, Naoko Kaibara, Naoko Yanagisawa, Fumiko Takenoya, Seiji Shioda

Journal of molecular neuroscience : MN 74 ( 1 ) 25 - 25 2024.02 [International journal]

Galanin-like peptide (GALP) is a neuropeptide that was first isolated and identified from the porcine hypothalamus. Studies have described an anti-obesity effect of GALP. We previously found that intracerebroventricular administration of GALP in mice resulted in an increase in respiratory exchange rate 12 to 16 h later. GALP may also affect glucose metabolism, but the detailed mechanism has not been elucidated. In this study, we investigated the effects of GALP on glucose and lipid metabolism in the liver. Nine-week-old male C57BL / 6 J mice were administered a single intracerebroventricular dose of saline or GALP and dissected 16 h later. There were no significant between-group differences in body weight and blood glucose levels. With regard to gene and protein expression, G6Pase associated with hepatic gluconeogenesis was significantly reduced in the GALP group. In addition, the hepatokines selenoprotein P and fetuin-A, which induce insulin resistance in the liver, were significantly decreased in the GALP group. These results suggest that intracerebroventricular administration of GALP decreases the expression of key hepatokines, thereby enhancing glucose metabolism.

DOI PubMed

Overexpression of UBE2E2 in mouse pancreatic β-cells leads to glucose intolerance via reduction of the β-cell mass.

Yoshitaka Sakurai, Naoto Kubota, Iseki Takamoto, Nobuhiro Wada, Masakazu Aihara, Takanori Hayashi, Tetsuya Kubota, Yuta Hiraike, Takayoshi Sasako, Harumi Nakao, Atsu Aiba, Yoko Chikaoka, Takeshi Kawamura, Takashi Kadowaki, Toshimasa Yamauchi

Diabetes 2023.12 [International journal]

Genome-wide association studies have identified several gene polymorphisms, including UBE2E2, associated with type 2 diabetes. Although UBE2E2 is one of the ubiquitin-conjugating enzymes (E2s) involved in the process of ubiquitin modifications, the pathophysiological roles of UBE2E2 in metabolic dysfunction are not yet understood. Herein, we showed upregulated UBE2E2 expression in the islets of a mouse model of diet-induced obesity. The diabetes risk allele of UBE2E2 (rs13094957) in non-coding regions was associated with upregulation of the UBE2E2 mRNA in the human pancreas. While glucose-stimulated insulin secretion was intact in the isolated islets, pancreatic β-cells-specific Ube2e2-transgenic (TG) mice exhibited reduced insulin secretion and decreased β-cell mass. In the TG mice, suppressed proliferation of β-cells before the weaning period and under the high-fat-diet condition was accompanied by elevated gene expression levels of p21, resulting in decreased postnatal β-cell mass expansion and compensatory β-cell hyperplasia, respectively. In the TG islets, proteomic analysis identified enhanced formation of various types of polyubiquitin chains, accompanied by increased expression of Nedd4 E3 ubiquitin-protein ligase. Ubiquitination assays showed that UBE2E2 mediated the elongation of ubiquitin chains by Nedd4. The data suggest that UBE2E2-mediated ubiquitin modifications in the β-cells play an important role in regulating glucose homeostasis and β-cell mass.

DOI PubMed

Fish oil-derived n-3 polyunsaturated fatty acids downregulate aquaporin 9 protein expression of liver and white adipose tissues in diabetic KK mice and 3T3-L1 adipocytes.

Yuzuru Iizuka, Satoshi Hirako, Hyounju Kim, Nobuhiro Wada, Yuki Ohsaki, Naoko Yanagisawa

The Journal of nutritional biochemistry 109514 - 109514 2023.10 [International journal]

Aquaporin 9 (AQP9) is an integral membrane protein that facilitates glycerol transport in hepatocytes and adipocytes. Glycerol is necessary as a substrate for gluconeogenesis in the physiological fasted state, suggesting that inhibiting AQP9 function may be beneficial for treating type 2 diabetes associated with fasting hyperglycemia. The n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are rich in fish oil and lower the risk of metabolic syndrome; however, the effects of EPA and DHA on AQP9 expression in obese and type 2 diabetes are unclear. The KK mouse is an animal model of obesity and type 2 diabetes because of the polymorphisms on leptin receptor gene, which results in a part of cause for obese and diabetic conditions. In this study, we determined the effect of fish oil-derived n-3 PUFA on AQP9 protein expression in the liver and white adipose tissue (WAT) of KK mice and mouse 3T3-L1 adipocytes. The expression of AQP9 protein in the liver, epididymal WAT, and inguinal WAT were markedly decreased following fish oil administration. We also demonstrated that n-3 PUFAs, such as DHA, and to a lesser extent EPA, downregulated AQP9 protein expression in 3T3-L1 adipocytes. Our results suggest that fish oil-derived n-3 PUFAs may regulate the protein expressions of AQP9 in glycerol metabolism-related organs in KK mice and 3T3-L1 adipocytes.

DOI PubMed

Association of Aquaporin 7 and 9 with Obesity and Fatty Liver in db/db Mice

Satoshi Hirako, Yoshihiro Wakayama, Hyounju Kim, Yuzuru Iizuka, Nobuhiro Wada, Naoko Kaibara, Mai Okabe, Satoru Arata, Akiyo Matsumoto

Zoological Science ( Zoological Society of Japan ) 40 ( 6 ) 2023.09

DOI

Docosapentaenoic acid-rich oil lowers plasma glucose and lipids in a mouse model of diabetes and mild obesity.

Satoshi Hirako, Takahiro Hirabayashi, Junko Shibato, Ai Kimura, Michio Yamashita, Yuzuru Iizuka, Nobuhiro Wada, Naoko Kaibara, Fumiko Takenoya, Seiji Shioda

Nutrition research (New York, N.Y.) 118 128 - 136 2023.08 [International journal]

Many studies have investigated the beneficial effects of n-3 polyunsaturated fatty acids, such as their potential for lowering lipid levels and reducing diabetes risk. However, few studies have specifically examined docosapentaenoic acid (DPA), an n-3 polyunsaturated fatty acid with limited availability in its pure form. We hypothesized that DPA would have lipid-lowering effects and improve insulin resistance in KK/Ta mice. To test our hypothesis, 7-week-old KK/Ta mice were fed a high-fat diet for 12 weeks to induce obesity before being divided into 3 groups and fed an experimental diet for 10 weeks. The experimental diets were: LSO, using lard and safflower oil as fat sources; SO, in which lard in the LSO diet was replaced with safflower oil; and DPA, in which lard in the LSO diet was replaced with DPA oil. After 10 weeks, plasma triglyceride and total cholesterol concentrations were significantly decreased in the DPA group, but not in the SO group. Sterol regulatory element-binding protein-1 and stearoyl-CoA desaturase-1 gene expressions involved in fatty acid synthesis in the liver were significantly lower in the DPA group compared with the LSO group. Plasma glucose concentrations were significantly decreased in both the SO group and the DPA group compared with the LSO group, whereas plasma insulin concentrations were significantly decreased in the DPA group alone. These results indicate that DPA has plasma lipid-lowering and hypoglycemic effects, possibly from suppression of fatty acid synthesis in the liver.

DOI PubMed

The sodium‐glucose co‐transporter 2 inhibitor tofogliflozin suppresses atherosclerosis through glucose lowering in ApoE‐deficient mice with streptozotocin‐induced diabetes

Masahiko Iwamoto, Tetsuya Kubota, Yoshitaka Sakurai, Nobuhiro Wada, Seiji Shioda, Toshimasa Yamauchi, Takashi Kadowaki, Naoto Kubota

Pharmacology Research & Perspectives ( Wiley ) 10 ( 4 ) e00971 2022.08 [Refereed] [International journal]

Epidemiological and animal studies have revealed that sodium-glucose cotransporter 2 (SGLT2) inhibitors suppress cardiovascular events in subjects with type 2 diabetes and atherosclerosis in animal models of diabetes. However, it still remains unclear if the anti-atherosclerotic effect of SGLT2 inhibitors is entirely dependent on their glucose-lowering effect. Tofogliflozin, a highly specific SGLT2 inhibitor, was administrated to apolipoprotein-E-deficient (ApoEKO) with streptozotocin (STZ)-induced diabetes and nondiabetic ApoEKO mice. After 6 weeks, samples were collected to investigate the histological changes and peritoneal macrophage inflammatory cytokine levels. Tofogliflozin suppressed atherosclerosis in the diabetic ApoEKO mice. The atherosclerosis lesion areas and accumulation of macrophages in these areas were reduced by tofogliflozin treatment. The expression levels of interleukin (IL)-1β and IL-6 in the peritoneal macrophages were significantly suppressed in the tofogliflozin-treated diabetic ApoEKO mice. Tofogliflozin treatment failed to inhibit atherosclerosis in the nondiabetic ApoEKO mice. No significant difference in the anti-atherosclerotic effects of insulin and tofogliflozin was observed between diabetic ApoEKO mice with equivalent degrees of glycemic control achieved with the two treatments. Insulin treatment significantly reduced the IL-1β and IL-6 expression levels in the peritoneal macrophages of the diabetic ApoEKO mice. Significant decrease of the LPS-stimulated IL-1β concentrations was also observed in the conditioned medium of the peritoneal macrophages collected from insulin- and tofogliflozin-treated diabetic ApoEKO mice. These results suggest that tofogliflozin suppresses atherosclerosis by improving glucose intolerance associated with inhibition of inflammation. Tofogliflozin suppresses atherosclerosis in ApoEKO mice with STZ-induced diabetes via its glucose-lowering effect.

DOI PubMed

Lack of Brain Insulin Receptor Substrate-1 Causes Growth Retardation, With Decreased Expression of Growth Hormone–Releasing Hormone in the Hypothalamus

Takanori Hayashi, Tetsuya Kubota, Inoue Mariko, Iseki Takamoto, Masakazu Aihara, Yoshitaka Sakurai, Nobuhiro Wada, Takashi Miki, Toshimasa Yamauchi, Naoto Kubota, Takashi Kadowaki

Diabetes ( American Diabetes Association ) 70 ( 8 ) 1640 - 1653 2021.08 [International journal]

Insulin receptor substrate-1 (Irs1) is one of the major substrates for insulin receptor and insulin-like growth factor-1 (IGF-1) receptor tyrosine kinases. Systemic Irs1-deficient mice show growth retardation, with resistance to insulin and IGF-1, although the underlying mechanisms remain poorly understood. For this study, we generated mice with brain-specific deletion of Irs1 (NIrs1KO mice). The NIrs1KO mice exhibited lower body weights, shorter bodies and bone lengths, and decreased bone density. Moreover, the NIrs1KO mice exhibited increased insulin sensitivity and glucose utilization in the skeletal muscle. Although the ability of the pituitary to secrete growth hormone (GH) remained intact, the amount of hypothalamic growth hormone-releasing hormone (GHRH) was significantly decreased and, accordingly, the pituitary GH mRNA expression levels were impaired in these mice. Plasma GH and IGF-1 levels were also lower in the NIrs1KO mice. The expression levels of GHRH protein in the median eminence, where Irs1 antibody staining is observed, were markedly decreased in the NIrs1KO mice. In vitro, neurite elongation after IGF-1 stimulation was significantly impaired by Irs1 downregulation in the cultured N-38 hypothalamic neurons. In conclusion, brain Irs1 plays important roles in the regulation of neurite outgrowth of GHRH neurons, somatic growth, and glucose homeostasis.

DOI PubMed

Leptin

Nobuhiro Wada

Handbook of Hormones ( Elsevier ) 573 - 575 2021

DOI

Alarin

Nobuhiro Wada

Handbook of Hormones ( Elsevier ) 361 - 362 2021

DOI

Galanin peptide family

Nobuhiro Wada

Handbook of Hormones ( Elsevier ) 353 - 354 2021

DOI

Effects of PACAP on Dry Eye Symptoms, and Possible Use for Therapeutic Application

Seiji Shioda, Fumiko Takenoya, Takahiro Hirabayashi, Nobuhiro Wada, Tamotsu Seki, Naoko Nonaka, Tomoya Nakamachi

Journal of Molecular Neuroscience ( Springer Science and Business Media {LLC} ) 68 ( 3 ) 420 - 426 2019.07

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Glucocorticoid receptor suppresses gene expression of Rev‐erbα (Nr1d1) through interaction with theCLOCKcomplex

Yuki Murayama, Naoya Yahagi, Yoshinori Takeuchi, Yuichi Aita, Zahra Mehrazad Saber, Nobuhiro Wada, EnXu Li, Xianying Piao, Yoshikazu Sawada, Akito Shikama, Yukari Masuda, Makiko Nishi-Tatsumi, Midori Kubota, Yoshihiko Izumida, Takafumi Miyamoto, Motohiro Sekiya, Takashi Matsuzaka, Yoshimi Nakagawa, Yoko Sugano, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Hiroaki Suzuki, Hiroaki Yagyu, Yasushi Kawakami, Hitoshi Shimano

FEBS Letters ( Wiley ) 593 ( 4 ) 423 - 432 2019.02

DOI

Regulation of Feeding Behavior and Energy Metabolism by Galanin-like Peptide (GALP): A Novel Strategy to Fight Against Obesity

Fumiko Takenoya, Satoshi Hirako, Nobuhiro Wada, Naoko Nonaka, Takahiro Hirabayashi, Haruaki Kageyama, Seiji Shioda

Current Pharmaceutical Design ( Bentham Science Publishers Ltd. ) 24 ( 33 ) 3926 - 3933 2019.01

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<b>Analgesic effect of mineral cream containing natural spa minerals for use on the </b><b>skin </b>

Takahiro HIRABAYASHI, Michio YAMASHITA, Nobuhiro WADA, Fumiko TAKENOYA, Hiroko IKEDA, Junzo KAMEI, Tomoo RYUSHI, Noriyuki YAMAMOTO, Seiji SHIODA

Biomedical Research ( Biomedical Research Press ) 39 ( 4 ) 215 - 222 2018.08

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Papers - WADA Nobuhiro