論文 - 後藤　伸子

Brain fractalkine-CX3CR1 signalling is anti-obesity system as anorexigenic and anti-inflammatory actions in diet-induced obese mice

Kawamura N., Katsuura G., Yamada-Goto N., Nakama R., Kambe Y., Miyata A., Furuyashiki T., Narumiya S., Ogawa Y., Inui A.

Scientific Reports （Scientific Reports）  12 （ 1 ）  2022年12月

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Fractalkine is one of the CX3C chemokine family, and it is widely expressed in the brain including the hypothalamus. In the brain, fractalkine is expressed in neurons and binds to a CX3C chemokine receptor 1 (CX3CR1) in microglia. The hypothalamus regulates energy homeostasis of which dysregulation is associated with obesity. Therefore, we examined whether fractalkine-CX3CR1 signalling involved in regulating food intake and hypothalamic inflammation associated with obesity pathogenesis. In the present study, fractalkine significantly reduced food intake induced by several experimental stimuli and significantly increased brain-derived neurotrophic factor (BDNF) mRNA expression in the hypothalamus. Moreover, tyrosine receptor kinase B (TrkB) antagonist impaired fractalkine-induced anorexigenic actions. In addition, compared with wild-type mice, CX3CR1-deficient mice showed a significant increase in food intake and a significant decrease in BDNF mRNA expression in the hypothalamus. Mice fed a high-fat diet (HFD) for 16 weeks showed hypothalamic inflammation and reduced fractalkine mRNA expression in the hypothalamus. Intracerebroventricular administration of fractalkine significantly suppressed HFD-induced hypothalamic inflammation in mice. HFD intake for 4 weeks caused hypothalamic inflammation in CX3CR1-deficient mice, but not in wild-type mice. These findings suggest that fractalkine-CX3CR1 signalling induces anorexigenic actions via activation of the BDNF-TrkB pathway and suppresses HFD-induced hypothalamic inflammation in mice.

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Activation of α7 nicotinic receptors suppresses sucrose addiction in mice

Kawamura N., Novianti E., Yamada-Goto N., Nakama R., Asakawa A., Katsuura G., Inui A.

Progress in Neuro-Psychopharmacology and Biological Psychiatry （Progress in Neuro-Psychopharmacology and Biological Psychiatry）  113 2022年03月

ISSN  02785846

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The mesolimbic dopamine system is important for the rewarding and motivational aspects of consuming rewarding and palatable food. Nicotinic receptors are present in the mesolimbic dopamine system and enhance the reinforcement of drugs of abuse. In this study, we examined the involvement of nicotine receptor subtypes in sucrose addiction in a sucrose preference paradigm. Sucrose preference and intake in mice increased in proportion to stepwise increases in sucrose concentrations. Moreover, sucrose preference and intake following sucrose withdrawal in mice were increased in comparison with the first set of trials. In the present study, α7, but not α4 and β2, nicotinic receptor subunit mRNA was decreased in the nucleus accumbens, but not in the hypothalamus, after sucrose withdrawal and subsequent sucrose intake. Administration of an agonist for α7, but not α4 and β2, nicotinic receptors suppressed the enhancement of sucrose preference and intake following sucrose withdrawal. These findings indicate that α7 nicotinic receptor activation suppresses sucrose addiction in a sucrose preference test in mice.

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Birth weight and risk factors for atherosclerosis-retrospective cohort study in Japanese workers.

Azegami T, Takeda A, Yokoyama H, Wainai Y, Hirose H, Makino S, Nishimura T, Goto N, Itoh H, Mori M.

J Hypertens 39   e170 - e171 2021年04月

共著, 査読有り

Impaired brain fractalkine-CX3CR1 signaling is implicated in cognitive dysfunction in diet-induced obese mice

Kawamura N., Katsuura G., Yamada-Goto N., Novianti E., Inui A., Asakawa A.

BMJ Open Diabetes Research and Care （BMJ Open Diabetes Research and Care）  9 （ 1 ）  2021年02月

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Introduction A diet high in saturated fat is well known to affect neuronal function and contribute to cognitive decline in experimental animals and humans. Fractalkine released from neurons acts on its receptor, CX3C chemokine receptor 1 (CX3CR1), in the microglia to regulate several brain functions. The present study addressed whether fractalkine-CX3CR1 signaling in the brain, especially the hippocampus, contributes to the cognitive deficits observed in diet-induced obese (DIO) mice. Research design and methods Mice were given 60% high-fat diet for 16 weeks. The expression of fractalkine and CX3CR1 in the hippocampus, amygdala and prefrontal cortex of DIO mice was analyzed. Cognitive ability in the Y-maze test and hippocampal glutamate receptors and synaptic markers were observed in DIO and CX3CR1 antagonist-treated mice. Regulation of fractalkine and CX3CR1 expression in the hippocampus was examined following administration of a selective insulin-like growth factor-1 (IGF-1) receptor inhibitor and a tyrosine receptor kinase B (TrkB) antagonist in normal mice. Results DIO mice exhibited significant cognitive deficits in the Y-maze test and decrease in fractalkine and CX3CR1 in the hippocampus and amygdala compared with mice fed a control diet (CD mice). Administration of the CX3CR1 antagonist 18a in normal mice induced significant cognitive deficits in the Y-maze test. DIO mice and CX3CR1 antagonist-treated mice exhibited significant decreases in protein levels of NMDA (N-methyl-D-aspartate) receptor subunit (NR2A), AMPA (α-amino-5-methyl-3-hydroxy-4-isoxazole propionate) receptor subunit (GluR1) and postsynaptic density protein 95 in the hippocampus compared with their respective controls. Furthermore, plasma IGF-1 and hippocampal brain-derived neurotrophic factor were significantly decreased in DIO mice compared with CD mice. Administration of a selective IGF-1 receptor inhibitor and a TrkB antagonist in normal mice significantly decreased fractalkine and CX3CR1 in the hippocampus. Conclusions These findings indicate that the cognitive decline observed in DIO mice is due, in part, to reduced fractalkine-CX3CR1 signaling in the corticolimbic system.

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Sars-cov-2 infection among medical institution faculty and healthcare workers in tokyo, japan

Nishimura T., Uwamino Y., Uno S., Kashimura S., Shiraki T., Kurafuji T., Morita M., Noguchi M., Azegami T., Yamada-Goto N., Murai-Takeda A., Yokoyama H., Kuwabara K., Kato S., Matsumoto M., Hirata A., Iida M., Harada S., Ishizaka T., Misawa K., Murata M., Saya H., Amagai M., Kitagawa Y., Takeuchi T., Mori M., Takebayashi T., Hasegawa N.

Internal Medicine （Internal Medicine）  60 （ 16 ） 2569 - 2575 2021年

ISSN  09182918

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Objective To consider effective measures against severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) infection in medical institutions, this study estimated the SARS-CoV-2 infection rate among healthcare workers (HCWs) in Tokyo, Japan, and determined the specific findings for mild coronavirus disease 2019 (COVID-19) cases. Methods This study analyzed the results of serologic tests to detect immunoglobulin G antibodies against SARS-CoV-2 and evaluated the demographic and clinical characteristics of the faculty and HCWs at a Tokyo medical institution in August 2020. The demographic and clinical characteristics of participants with antibody-positive results were compared to those of participants with antibody-negative results. Materials This study recruited 2,341 faculty and HCWs at a Tokyo medical institution, 21 of whom had a COVID-19 history. Results Of the 2,320 participants without a COVID-19 history, 20 (0.862%) had positive serologic test results. A fever and dysgeusia or dysosmia occurred with greater frequency among the participants with positive test results than in those with negative results [odds ratio (OR), 5.475; 95% confidence interval (CI), 1.960-15.293 and OR, 24.158; 95% CI, 2.693-216.720, respectively]. No significant difference was observed in the positivity rate between HCWs providing medical care for COVID-19 patients using adequate protection and other HCWs (OR, 2.514; 95% CI, 0.959-6.588). Conclusion To reduce the risk of COVID-19 spread in medical institutions, faculty and HCWs should follow standard and necessary transmission-based precautions, and those with a fever and dysgeusia or dysosmia should excuse themselves from work as soon as possible.

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The distributions of hematologic and biochemical values in healthy high-school adolescents in Japan.

Azegami T, Nishimura T, Murai-Takeda A, Yamada-Goto N, Sato Y, Mori M.

PLoS One 15 （ 11 ） e0242272 2020年11月

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The Impact of Laparoscopic Sleeve Gastrectomy with Duodenojejunal Bypass on Intestinal Microbiota Differs from that of Laparoscopic Sleeve Gastrectomy in Japanese Patients with Obesity

Kikuchi R., Irie J., Yamada-Goto N., Kikkawa E., Seki Y., Kasama K., Itoh H.

Clinical Drug Investigation （Clinical Drug Investigation）  38 （ 6 ） 545 - 552 2018年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  11732563

　概要を見る

© 2018, Springer International Publishing AG, part of Springer Nature. Background and Objectives: Bariatric surgery improves metabolic diseases and alters the intestinal microbiota in animals and humans, but different procedures reportedly have different impacts on the intestinal microbiota. We developed laparoscopic sleeve gastrectomy with duodenojejunal bypass (LSG-DJB) as an alternative to laparoscopic Roux-en-Y gastric bypass (LRYGB) in addition to laparoscopic sleeve gastrectomy (LSG) for Japanese patients with obesity. We investigated the precise change in the intestinal microbiota induced by these procedures in the present study. Methods: A prospective observational study of 44 Japanese patients with obesity was conducted [22 patients underwent LSG, 18 underwent LSG-DJB, and 4 underwent laparoscopic adjustable gastric banding (LAGB)]. The patients’ clinical parameters and intestinal microbiota were investigated before and for 6 months after surgery. The microbiota was analyzed by a 16S rDNA method. Results: LSG and LSG-DJB significantly improved the metabolic disorders in the patients with obesity. The proportion of the phylum Bacteroidetes and order Lactobacillales increased significantly in the LSG group, and that of the order Enterobacteriales increased significantly in the LSG-DJB group. Conclusions: LSG and LSG-DJB improved obesity and type 2 diabetes in Japanese patients with obesity, but the impact of LSG-DJB on the intestinal microbiota differed from that of LSG. This difference in the impact on the intestinal environment could explain the different efficacies of LSG and LSG-DJB in terms of their ability to resolve metabolic disorders in the clinical setting.

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Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system. Neuropeptides.

Yamada-Goto N, Ochi Y, Katsuura G, Yamashita Y, Ebihara K, Noguchi M, Fujikura J, Taura D, Sone M, Hosoda K, Gottschall PE, Nakao K.

Neuropeptides 65   10 - 20 2017年10月

研究論文（学術雑誌）, 共著, 査読有り

Brain-specific natriuretic peptide receptor-B deletion attenuates high-fat diet-induced visceral and hepatic lipid deposition in mice.

Yamashita Y, Yamada-Goto N, Katsuura G, Ochi Y, Kanai Y, Miyazaki Y, Kuwahara K, Kanamoto N, Miura M, Yasoda A, Ohinata K, Inagaki N, Nakao K.

Peptides 81   38 - 50 2016年06月

研究論文（学術雑誌）, 共著, 査読有り

Intracerebroventricular administration of C-type natriuretic peptide suppresses food intake via activation of the melanocortin System in Mice.

Yamada-Goto N, Katsuura G, Ebihara K, Inuzuka M, Ochi Y, Yamashita Y, Kusakabe T, Yasoda A, Satoh-Asahara N, Ariyasu H, Hosoda K, Nakao K.

Diabetes 62   1500 - 1504 2013年05月

研究論文（学術雑誌）, 共著, 査読有り

Salivary cortisol levels are associated with outcomes of weight reduction therapy in obese Japanese patients.

Himeno A, Satoh-Asahara N, Usui T, Wada H, Tochiya M, Kono S, Yamada-Goto N, Katsuura G, Hasegawa K, Nakao K, Shimatsu A

Metabolism 61   255 - 261 2012年08月

共著, 査読有り

Impairment of fear-conditioning responses and changes of brain neurotrophic factors in diet-induced obese mice.

Yamada-Goto N, Katsuura G, Ochi Y, Ebihara K, Kusakabe T, Hosoda K, Nakao K.

Journal of Neuroendocrinolgy 24   1120 - 1125 2012年08月

研究論文（学術雑誌）, 共著, 査読有り

Salivary cortisol levels are associated with outcomes of weight reduction therapy in obese Japanese patients.

Himeno A, Satoh-Asahara N, Usui T, Wada H, Tochiya M, Kono S, Yamada-Goto N, Katsuura G, Hasegawa K, Nakao K, Shimatsu A.

Metabolism 61   255 - 261 2012年02月

研究論文（学術雑誌）, 共著, 査読有り

Impaired CNS Leptin Action Is Implicated in Depression Associated with Obesity.

Yamada N, Katsuura G, Ochi Y, Ebihara K, Kusakabe T, Hosoda K, Nakao K.

Endocrinology 152 （ 7 ） 2634 - 2643 2011年07月

研究論文（学術雑誌）, 共著, 査読有り

C-type natriuretic peptide as a new regulator of food intake and energy expenditure.

Inuzuka M, Tamura N, Yamada N, Katsuura G, Oyamada N, Taura D, Sonoyama T, Fukunaga Y, Ohinata K, Sone M, Nakao K.

Endocrinology 151   3633 - 3642 2010年08月

研究論文（学術雑誌）, 共著, 査読有り

Orexin increase mRNA expressions of neurotrophin-3 in rat primary cortical neuron culture neuron cultures.

Yamada N, Katsuura G, Tatsuno I, Kawahara S, Ebihara K, Saito Y, Nakao K.

Neuroscience Letters 450 （ 2 ） 132 - 135 2009年01月

研究論文（学術雑誌）, 共著, 査読有り

Orexin decreases mRNA expressions of NMDA and AMPA receptor subunits in rat primary neuron cultures

Yamada N, Katsuura G, Tatsuno I, Asaki T, Kawahara S, Ebihara K, Saito Y, Nakao K.

Peptides 29 （ 9 ） 1582 - 1587 2008年09月

研究論文（学術雑誌）, 共著, 査読有り

Tumor suppressor candidate 5 (TUC5) is expressed in brown adipocytes.

Tumor suppressor candidate 5 (TUC5) is expressed in brown adipocytes.

Biochemical and biophysical research communications 360 （ 1 ） 139 - 145 2007年08月

研究論文（学術雑誌）, 共著, 査読有り

Anticonvulsant hypersensitivity syndrome with marked eosinophilia in treatment of diabetic neuropathy.

Yamada N, Kaneko K, Tatsuno I.

Diabetes Care 25 （ 6 ） 1099 - 1100 2002年06月

研究論文（学術雑誌）, 共著, 査読有り

抗痙攣剤過敏性症候群と低Na血症を起こし,Human Herpes virus 6の再活性化が認められた糖尿病性神経障害の一例.

山田伸子、龍野一郎、金子堅太郎、吉田知彦、布施まさみ、大塚優子、竹尾愛理、内田大学、田中知明、橋本尚武、齋藤康.

日本内分泌学会雑誌 78 （ supplement ） 58 - 60 2002年01月

研究論文（学術雑誌）, 共著, 査読有り