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フロンティア科学総合研究センター 生理活性物質研究部門生理活性物質探索病態解析分野 |
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准教授 |
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論文 【 表示 ／ 非表示 】
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Thermoregulatory role of ghrelin in the induction of torpor under a restricted feeding condition
Sato T., Oishi K., Koga D., Ida T., Sakai Y., Kangawa K., Kojima M.
Scientific Reports 11 ( 1 ) 17954 2021年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
Ghrelin, a circulating orexigenic hormone secreted from the stomach, stimulates appetite and food intake by activating the hypothalamic arcuate nucleus. Administration of exogenous ghrelin exerts anabolic effects, causing weight gain, increased adiposity, and decreased metabolism. Body temperature (BT), which is determined by the balance of heat production and heat loss, must be strictly regulated to maintain proper cellular function and metabolism. However, the role of ghrelin in thermoregulation remains unclear. In this study, we found that ghrelin was essential for decreasing BT when mice are placed under calorie restriction. Elevated ghrelin concentrations induced by fasting correlated with significant decreases in BT, a hibernation-like state called torpor. Ghrelin-deficient (Ghrl−/−) animals could not enter torpor. The BT of Ghrl−/− mice also remained high under restricted feeding, but the animals gradually entered precipitous hypothermia, indicating thermoregulatory impairment. These effects of ghrelin on thermoregulation were the result of suppression of sympathetic nervous system activity input to brown adipose tissue; in the absence of ghrelin, it was not possible to suppress uncoupling protein 1 (ucp1) expression and decrease BT in low-energy states. Together, these findings demonstrate that ghrelin is an essential circulating hormone involved in lowering BT.
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Analyses of molecular characteristics and enzymatic activities of ovine hsd17b3
Islam M.S., Uwada J., Hayashi J., Kikuya K.I., Muranishi Y., Watanabe H., Yaegashi K., Hasegawa K., Ida T., Sato T., Imamichi Y., Kitano T., Miyashiro Y., Khan R.I., Takahashi S., Umezawa A., Suzuki N., Sekiguchi T., Yazawa T.
Animals 11 ( 10 ) 2021年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Animals
17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) converts androstenedione (A4) into testosterone (T), which regulates sex steroid production. Because various mutations of the HSD17B3 gene cause disorder of sex differentiation (DSD) in multiple mammalian species, it is very important to reveal the molecular characteristics of this gene in various species. Here, we revealed the open reading frame of the ovine HSD17B3 gene. Enzymatic activities of ovine HSD17B3 and HSD17B1 for converting A4 to T were detected using ovine androgen receptor-mediated transactivation in reporter assays. Although HSD17B3 also converted estrone to estradiol, this activity was much weaker than those of HSD17B1. Although ovine HSD17B3 has an amino acid sequence that is conserved compared with other mammalian species, it possesses two amino acid substitutions that are consistent with the reported variants of human HSD17B3. Substitutions of these amino acids in ovine HSD17B3 for those in human did not affect the enzymatic activities. However, enzymatic activities declined upon missense mutations of the HSD17B3 gene associated with 46,XY DSD, affecting amino acids that are conserved between these two species. The present study provides basic information and tools to investigate the molecular mechanisms behind DSD not only in ovine, but also in various mammalian species.
DOI： 10.3390/ani11102876
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Kato J., Kawagoe Y., Jiang D., Ida T., Shimamoto S., Igarashi K., Kitamura K.
Peptides 142 2021年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Peptides
Plasma levels of the hypotensive peptides of adrenomedullin and atrial and B-type natriuretic peptides (AM, ANP, BNP) are possible biomarkers for cardiovascular diseases. Increased variability of body mass index (BMI) over a certain period of time has been reported to be associated with cardiovascular morbidity or mortality. The aim of this study is to examine clinical significance of those hypotensive peptides as biomarkers by analyzing the relationship between plasma levels of the peptides and year-by-year variability of BMI in the general population without overt cardiovascular diseases. The subjects were 427 local residents (141 males and 286 females) attending their annual health check-up, who had been examined at least 5 times over the preceding period of 10 years. They were divided into two groups of low or high variability by the median of coefficient of variation (CV) of BMI values for each gender. Plasma AM levels of those with high year-by-year variability of BMI were significantly increased, as compared to the group with low variability, in both genders; meanwhile, such a difference was not noted in plasma levels of the natriuretic peptides. No significant differences were found in the basal parameters, which could affect plasma AM level, such as age, BMI, blood pressure or serum creatinine, between two groups. In conclusion, increase in plasma AM was associated with high year-by-year variability of BMI in the general population without overt heart disease. This relationship between the two suggests that increased plasma AM level is a cardiovascular risk marker.
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Characterization of putative tachykinin peptides in Caenorhabditis elegans
Sakai N., Ohno H., Yoshida M., Iwamoto E., Kurogi A., Jiang D., Sato T., Miyazato M., Kojima M., Kato J., Ida T.
Biochemical and Biophysical Research Communications 559 197 - 202 2021年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Biochemical and Biophysical Research Communications
Tachykinin-like peptides, such as substance P, neurokinin A, and neurokinin B, are among the earliest discovered and best-studied neuropeptide families, and research on them has contributed greatly to our understanding of the endocrine control of many physiological processes. However, there are still many orphan tachykinin receptor homologs for which cognate ligands have not yet been identified, especially in small invertebrates, such as the nematode Caenorhabditis elegans (C. elegans). We here show that the C. elegans nlp-58 gene encodes putative ligands for the orphan G protein-coupled receptor (GPCR) TKR-1, which is a worm ortholog of tachykinin receptors. We first determine, through an unbiased biochemical screen, that a peptide derived from the NLP-58 preprotein stimulates TKR-1. Three mature peptides that are predicted to be generated from NLP-58 show potent agonist activity against TKR-1. We designate these peptides as C. elegans tachykinin (CeTK)-1, −2, and −3. The CeTK peptides contain the C-terminal sequence GLR-amide, which is shared by tachykinin-like peptides in other invertebrate species. nlp-58 exhibits a strongly restricted expression pattern in several neurons, implying that CeTKs behave as neuropeptides. The discovery of CeTKs provides important information to aid our understanding of tachykinin-like peptides and their functional interaction with GPCRs.
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Yazawa T., Inaba H., Imamichi Y., Sekiguchi T., Uwada J., Islam M.S., Orisaka M., Mikami D., Ida T., Sato T., Miyashiro Y., Takahashi S., Khan M.R.I., Suzuki N., Umezawa A., Kitano T.
Frontiers in Endocrinology 12 2021年3月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Frontiers in Endocrinology
Although 11-ketotestosterone (11KT) and testosterone (T) are major androgens in both teleosts and humans, their 5α-reduced derivatives produced by steroid 5α-reductase (SRD5A/srd5a), i.e., 11-ketodihydrotestosterone (11KDHT) and 5α-dihydrotestosterone (DHT), remains poorly characterized, especially in teleosts. In this study, we compared the presence and production of DHT and 11KDHT in Japanese eels and humans. Plasma 11KT concentrations were similar in both male and female eels, whereas T levels were much higher in females. In accordance with the levels of their precursors, 11KDHT levels did not show sexual dimorphism, whereas DHT levels were much higher in females. It is noteworthy that plasma DHT levels in female eels were higher than those in men. In addition, plasma 11KDHT was undetectable in both sexes in humans, despite the presence of 11KT. Three srd5a genes (srd5a1, srd5a2a and srd5a2b) were cloned from eel gonads. All three srd5a genes were expressed in the ovary, whereas only both srd5a2 genes were expressed in the testis. Human SRD5A1 was expressed in testis, ovary and adrenal, whereas SRD5A2 was expressed only in testis. Human SRD5A1, SRD5A2 and both eel srd5a2 isoforms catalyzed the conversion of T and 11KT into DHT and 11KDHT, respectively, whereas only eel srd5a1 converted T into DHT. DHT and 11KDHT activated eel androgen receptor (ar)α-mediated transactivation as similar fashion to T and 11KT. In contrast, human AR and eel arβ were activated by DHT and11KDHT more strongly than T and 11KT. These results indicate that in teleosts, DHT and 11KDHT may be important 5α-reduced androgens produced in the gonads. In contrast, DHT is the only major 5α-reduced androgens in healthy humans.
MISC 【 表示 ／ 非表示 】
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消化管関連ペプチドが拓く恒常性フロンティア 招待あり
佐藤貴弘、井田隆徳、関口俊男、中町智哉、児島将康
実験医学 37 ( 3 ) 1 - 8 2019年
記述言語：日本語 掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）
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Role of biological rhythms in the performance of physical activity 招待あり 査読あり
Sato T, Ida T, Kojima M
The Journal of Physical Fitness and Sports Medicine 6 ( 3 ) 125 - 134 2017年3月
記述言語：英語 掲載種別：記事・総説・解説・論説等（学術雑誌）
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モデル生物を利用した新規摂食調節ペプチドの探索
井田隆徳
生物科学 2016年3月
記述言語：日本語 掲載種別：記事・総説・解説・論説等（学術雑誌） 出版者・発行元：農山漁村文化協会
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Sano H., Nakamura A., Texada M., Truman J., Ishimoto H., Kamikouchi A., Nibu Y., Kume K., Ida T., Kojima M.
PLoS Genetics 11 ( 9 ) 2015年9月
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摂食調節ペプチドと飢餓応答
佐藤貴弘、井田隆徳、児島将康
The lipid 26 ( 1 ) 35 - 39 2015年1月
記述言語：日本語 掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア） 出版者・発行元：メディカルレビュー社
講演・口頭発表等 【 表示 ／ 非表示 】
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新規生理活性ペプチドの探索と分泌様式の研究
井田隆徳
第126回⽇本解剖学会総会・全国学術集会・第98回⽇本⽣理学会⼤会
開催年月日： 2021年3月29日
記述言語：英語 会議種別：口頭発表（一般）
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Evaluation of enzymatic activity of various HSD1783 mutants using androgen receptor-mediated transactivation 国際会議
Yazawa T, Sato T, Ida T
ENDO 2021
開催年月日： 2021年3月20日
記述言語：英語 会議種別：ポスター発表
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Evaluation of enzymatic activity of human HSD17B3 using androgen receptor-mediated transactivation 国際会議
Yazawa T, Sato T, Ida T
ICE VIRTUAL 2021
開催年月日： 2021年2月24日
記述言語：英語 会議種別：ポスター発表
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新規生理活性ペプチドの発見と応用
井田隆徳
第11回ペプチド・ホルモン研究会
開催年月日： 2020年12月5日
記述言語：英語 会議種別：口頭発表（一般）
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新規生理活性ペプチドdRYamide, LURY-1の発見
井田隆徳、矢澤隆志、佐藤貴弘
第163回日本獣医学会学術集会
開催年月日： 2020年9月14日
記述言語：日本語 会議種別：ポスター発表
受賞 【 表示 ／ 非表示 】
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日本獣医学会生理学・生化学分科会奨励賞
2010年9月 日本獣医学会
井田隆徳
受賞区分：国内学会・会議・シンポジウム等の賞 受賞国：日本国
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11th International Conference on Human-Animal Interactions.Best Poster Award
2007年10月 IAHAIO
Yoshidomi Y, Ikeda Y, Satoh H, Sekino R, Ida T, Hisatomi I, Nakatsuka K, Misawa N
受賞区分：国際学会・会議・シンポジウム等の賞 受賞国：日本国
科研費（文科省・学振）獲得実績 【 表示 ／ 非表示 】
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難治性の神経因性疼痛を抑制する脳由来新規生理活性物質の構造決定と生理作用の解析
2020年04月
科学研究費補助金 基盤研究(C)
担当区分：研究分担者
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難治性の神経因性疼痛を抑制する脳由来新規生理活性物質の構造決定と生理作用の解析
研究課題/領域番号：20K0776801 2020年 - 9999年
基盤研究(C)
担当区分：研究分担者
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新規NPY様RYamideペプチドの発見と食欲調節機構の解析
2017年04月 - 2020年03月
科学研究費補助金 基盤研究(C)
担当区分：研究代表者
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昆虫における食欲促進/減退を引き起こす生理活性ペプチドの発見
2014年04月 - 2017年03月
科学研究費補助金 基盤研究(C)
担当区分：研究代表者
昆虫における食欲促進/減退を引き起こす生理活性ペプチドの発見し解析する
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食欲・脂肪代謝調節に関係する新規生理活性ペプチドの探索
2013年04月 - 2015年03月
科学研究費補助金 新学術領域（研究領域提案型）
食欲・脂肪代謝調節に関係する新規生理活性ペプチドの探索し解析する
その他競争的資金獲得実績 【 表示 ／ 非表示 】
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新規生理活性ペプチドの探索
2010年01月 - 2015年03月
文部科学省 特色ある大学教育支援プログラム
担当区分：研究代表者 資金種別：競争的資金
新規生理活性ペプチドの探索
その他研究活動 【 表示 ／ 非表示 】
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食鳥処理施設での脳のサンプリング
2019年07月
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食鳥処理施設での肝臓のサンプリング
2018年06月
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食肉処理施設における膵臓のサンプリング
2017年07月
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食鳥処理施設での脳のサンプリング
2017年05月
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食鳥処理場における新規生理活性ペプチド、ステロイドホルモンの探索
2017年03月
食鳥処理場においてウシ、ブタ、ニワトリから様々な臓器をサンプリングし、新規生理活性ペプチド、ステロイドホルモンの探索を行う。