Papers - WADA Nobuhiro

Effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on weight loss is partly mediated by liver-brain-adipose neurocircuitry

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

Biochemical and Biophysical Research Communications ( Elsevier {BV} )  493 ( 1 ) 40 - 45  2017.11  [International journal]

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Sodium-glucose cotransporter 2 (SGLT2) inhibitors have both anti-diabetic and anti-obesity effects. However, the precise mechanism of the anti-obesity effect remains unclear. We previously demonstrated that the glycogen depletion signal triggers lipolysis in adipose tissue via liver-brain-adipose neurocircuitry. In this study, therefore, we investigated whether the anti-obesity mechanism of SGLT2 inhibitor is mediated by this mechanism. Diet-induced obese mice were subjected to hepatic vagotomy (HVx) or sham operation and loaded with high fat diet containing 0.015% tofogliflozin (TOFO), a highly selective SGLT2 inhibitor, for 3 weeks. TOFO-treated mice showed a decrease in fat mass and the effect of TOFO was attenuated in HVx group. Although both HVx and sham mice showed a similar level of reduction in hepatic glycogen by TOFO treatment, HVx mice exhibited an attenuated response in protein phosphorylation by protein kinase A (PKA) in white adipose tissue compared with the sham group. As PKA pathway is known to act as an effector of the liver-brain-adipose axis and activate triglyceride lipases in adipocytes, these results indicated that SGLT2 inhibition triggered glycogen depletion signal and actuated liver-brain-adipose axis, resulting in PKA activation in adipocytes. Taken together, it was concluded that the effect of SGLT2 inhibition on weight loss is in part mediated via the liver-brain-adipose neurocircuitry.

DOI PubMed

Activation of SF1 Neurons in the Ventromedial Hypothalamus by DREADD Technology Increases Insulin Sensitivity in Peripheral Tissues

Eulalia A. Coutinho, Shiki Okamoto, Ayako Wendy Ishikawa, Shigefumi Yokota, Nobuhiro Wada, Takahiro Hirabayashi, Kumiko Saito, Tatsuya Sato, Kazuyo Takagi, Chen-Chi Wang, Kenta Kobayashi, Yoshihiro Ogawa, Seiji Shioda, Yumiko Yoshimura, Yasuhiko Minokoshi

Diabetes ( American Diabetes Association )  66 ( 9 ) 2372 - 2386  2017.09

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The ventromedial hypothalamus (VMH) regulates glucose and energy metabolism in mammals. Optogenetic stimulation of VMH neurons that express steroidogenic factor 1 (SF1) induces hyperglycemia. However, leptin acting via the VMH stimulates whole-body glucose utilization and insulin sensitivity in some peripheral tissues, and this effect of leptin appears to be mediated by SF1 neurons. We examined the effects of activation of SF1 neurons with DREADD (designer receptors exclusively activated by designer drugs) technology. Activation of SF1 neurons by an intraperitoneal injection of clozapine-N-oxide (CNO), a specific hM3Dq ligand, reduced food intake and increased energy expenditure in mice expressing hM3Dq in SF1 neurons. It also increased whole-body glucose utilization and glucose uptake in red-type skeletal muscle, heart, and interscapular brown adipose tissue, as well as glucose production and glycogen phosphorylase a activity in the liver, thereby maintaining blood glucose levels. During hyperinsulinemic-euglycemic clamp, such activation of SF1 neurons increased insulin-induced glucose uptake in the same peripheral tissues and tended to enhance insulin-induced suppression of glucose production by suppressing gluconeogenic gene expression and glycogen phosphorylase a activity in the liver. DREADD technology is thus an important tool for studies of the role of the brain in the regulation of insulin sensitivity in peripheral tissues.

DOI

The relationship between aquaglyceroporin expression and development of fatty liver in diet-induced obesity and ob/ob mice

Satoshi Hirako, Yoshihiro Wakayama, Hyounju Kim, Yuzuru Iizuka, Akiyo Matsumoto, Nobuhiro Wada, Ai Kimura, Mai Okabe, Junichi Sakagami, Mamiko Suzuki, Fumiko Takenoya, Seiji Shioda

Obesity Research & Clinical Practice ( Elsevier {BV} )  10 ( 6 ) 710 - 718  2016.11  [International journal]

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Aquaporin (AQP) 7 and AQP9 are subcategorised as aquaglyceroporins which transport glycerin in addition to water. These AQPs may play a role in the homeostasis of energy metabolism. We examined the effect of AQP7, AQP9, and lipid metabolism-related gene expression in obese mice. In diet-induced obese (DIO) mice, excess lipid accumulated in the liver, which was hyperleptinemic and hyperinsulinemic. Hepatic AQP9 gene expression was significantly increased in both DIO and ob/ob mice compared to controls. The mRNA expression levels of fatty acid and triglyceride synthesis-related genes and fatty acid β oxidation-related genes in the liver were also higher in both mouse models, suggesting that triglyceride synthesis in this organ is promoted as a result of glycerol release from adipocytes. Adipose AQP7 and AQP9 gene expressions were increased in DIO mice, but there was no difference in ob/ob mice compared to wild-type mice. In summary, adipose AQP7 and AQP9 gene expressions are increased by diet-induced obesity, indicating that this is one of the mechanisms by which lipid accumulates in response to a high fat diet, not the genetic mutation of ob/ob mice. Hepatic AQP9 gene expression was increased in both obesity model mice. AQP7 and AQP9 therefore have the potential of defining molecules for the characterisation of obesity or fatty liver and may be a target molecules for the treatment of those disease.

DOI PubMed

Pleiotropic and retinoprotective functions of PACAP

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

Anatomical Science International ( Springer Science and Business Media {LLC} )  91 ( 4 ) 313 - 324  2016.09

DOI

Hepatic lipid accumulation is ameliorated in obese KK mice by dietary sei whale oil

Satoshi Hirako, Mamiko Suzuki, Hyounju Kim, Yuzuru Iizuka, Akiyo Matsumoto, Nobuhiro Wada, Mai Okabe, Fumiko Takenoya, Genta Yasunaga, Satoru Yamanaka, Akira Miyazaki, Seiji Shioda

FISHERIES SCIENCE ( SPRINGER JAPAN KK )  82 ( 3 ) 509 - 517  2016.05  [Refereed]

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Whale oil (WO) contains n-3 polyunsaturated fatty acids (PUFAs), but the effects of whale oil intake on lipid metabolism have remained unclear. We examined the influence of WO on lipid metabolism in obese KK mice. Male KK mice were fed a high-fat diet for 12 weeks to induce obesity. The mice were then given free access to a different diet for 10 weeks: the lard/safflower oil (LSO) diet consisted of 25 energy% (en%) LSO (6:4), the WO diet consisted of 25 en% WO, and the fish oil (FO) diet consisted of 11 en% FO plus 14 en% LSO. The n-3 PUFA content of the FO diet was the same as that in the WO diet. In the WO and FO groups, the total plasma cholesterol level was significantly decreased compared with that in the LSO group. The number of lipid droplets in liver specimens was also lower in the WO and FO groups, and the hepatic triglyceride and total cholesterol levels were decreased in these groups compared with the LSO group. Hepatic mRNA levels of fatty acid synthase, and stearoyl-CoA desaturase 1, which are fatty acid synthesis-related genes, were decreased in the WO and FO groups. No significant differences were observed between the WO and FO groups. Taken together, these results indicate that WO intake inhibits lipid accumulation in the liver by reducing fatty acid biosynthesis.

DOI

神経ペプチドGALPによる末梢組織での脂質代謝調節作用

平子 哲史, 影山 晴秋, 竹ノ谷 文子, 和田 亘弘, 塩田 清二

New Diet Therapy ( (一社)日本臨床栄養協会 )  31 ( 2 ) 182 - 182  2015.09

Neuropeptide W-Induced Hypophagia is Mediated Through Corticotropin-Releasing Hormone-Containing Neurons

Fumiko Takenoya, Lihua Wang, Haruaki Kageyama, Satoshi Hirako, Nobuhiro Wada, Hirofumi Hashimoto, Yoichi Ueta, Junichi Sakagami, Naoko Nonaka, Seiji Shioda

Journal of Molecular Neuroscience ( Springer Science and Business Media {LLC} )  56 ( 4 ) 789 - 798  2015.08

DOI

Ghrelin suppresses proliferation of fetal neural progenitor cells, and induces their differentiation into neurons

Jun Watanabe, Minako Matsumoto, Haruaki Kageyama, Norimitsu Murai, Shun Sasaki, Satoshi Hirako, Nobuhiro Wada, Satoru Arata, Seiji Shioda

Peptides ( Elsevier {BV} )  69   40 - 46  2015.07

DOI

Autonomic nervous system-mediated effects of GALP on energy metabolism in liver

Shioda Seiji, Hirako Satoshi, Wada Nobuhiro, Takenoya Fumiko

JOURNAL OF PHARMACOLOGICAL SCIENCES   128 ( 3 ) S66  2015.07  [Refereed]

Interactive Effect of Galanin-like Peptide (GALP) And Spontaneous Exercise On Energy Metabolism In Mouse

Takenoya Fumiko, Hirako Satoshi, Wada Nobuhiro, Yamamoto Noriyuki, Wada Tadashi, Ryushi Tomoo, Kageyama Haruaki, Shioda Seiji

MEDICINE AND SCIENCE IN SPORTS AND EXERCISE   47 ( 5 ) 72  2015.05  [Refereed]

DOI

Leptin and its receptors

Nobuhiro Wada, Satoshi Hirako, Fumiko Takenoya, Haruaki Kageyama, Mai Okabe, Seiji Shioda

Journal of Chemical Neuroanatomy ( Elsevier {BV} )  61-62   191 - 199  2014.11  [Refereed]  [Invited]

Authorship：   Lead author

DOI

ENERGY METABOLISM REGULATION BY INTRA CEREBROVENTRICULAR AND INTRANASAL ADMINISTRATION OF GALP

Satoshi Hirako, Haruaki Kageyama, Fumiko Takenoya, Nobuhiro Wada, Ai Kimura, Mai Okabe, Shioda Seiji

JOURNAL OF MOLECULAR NEUROSCIENCE ( HUMANA PRESS INC )  53   S165 - S165  2014.08  [Refereed]

Neuronal circuits involving neuropeptide Y in hypothalamic arcuate nucleus-mediated feeding regulation

Haruaki Kageyama, Fumiko Takenoya, Satoshi Hirako, Nobuhiro Wada, Yuri Kintaka, Shuji Inoue, Eiji Ota, Tetsuo Ogawa, Seiji Shioda

Neuropeptides ( Elsevier {BV} )  46 ( 6 ) 285 - 289  2012.12

DOI

Neuropeptide W

Fumiko Takenoya, Haruaki Kageyama, Satoshi Hirako, Eiji Ota, Nobuhiro Wada, Tomoo Ryushi, Seiji Shioda

Frontiers in Endocrinology ( Frontiers Media {SA} )  3  2012

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