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4. Adaptive gene expression of alternative splicing variants of PGC-1α regulates whole-body energy metabolism

Author

Nomura, Kazuhiro, Kinoshita, Shinichi, Mizusaki, Nao, Senga, Yoko, Sasaki, Tsutomu, Kitamura, Tadahiro, Sakaue, Hiroshi, Emi, Aki, Hosooka, Tetsuya, Matsuo, Masahiro, Okamura, Hitoshi, Amo, Taku, Wolf, Alexander M., Kamimura, Naomi, Ohta, Shigeo, Itoh, Tomoo, Hayashi, Yoshitake, Kiyonari, Hiroshi, Krook, Anna, Zierath, Juleen R., Kasuga, Masato, and Ogawa, Wataru

Published
2024
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6. Higher Frequency of Premature Atrial Contractions Correlates With Atrial Fibrillation Detection after Cryptogenic Stroke

Author

Shimada, Yuki, Todo, Kenichi, Doijiri, Ryosuke, Yamazaki, Hidekazu, Sonoda, Kazutaka, Koge, Junpei, Iwata, Tomonori, Ueno, Yuji, Yamagami, Hiroshi, Kimura, Naoto, Morimoto, Masafumi, Kondo, Daisuke, Koga, Masatoshi, Nagata, Eiichiro, Miyamoto, Nobukazu, Kimura, Yoko, Gon, Yasufumi, Okazaki, Shuhei, Sasaki, Tsutomu, Mochizuki, Hideki, Sugiyama, Shintaro, Ohara, Mariko, Ikegami, Takeshi, Wadayama, Tomoya, Murakami, Yasutaka, Sakurai, Rei, Moriyama, Takuya, Oi, Kiyotaka, Ikenouchi, Hajime, Yamaguchi, Eriko, Egashira, Shuhei, Takizawa, Shunya, Honma, Kazunari, Nakayama, Taira, Kadokura, Ayana, Hanano, Hideyuki, and Yamamoto, Shiro

Published
2024
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13. CREB coactivator CRTC1 in melanocortin‐4 receptor‐expressing cells regulate dietary fat intake.

Author

Matsumura, Shigenobu, Fujisawa, Miyu, Fujiwara, Mizuki, Okayama, Houko, Marutani, Miona, Nousou, Eri, Sasaki, Tsutomu, and Harada, Naoki

Abstract

Cyclic adenosine monophosphate‐response element‐binding protein‐1‐regulated transcription coactivator‐1 (CRTC1), a cytoplasmic coactivator that translocates to the nucleus in response to cAMP, is associated with obesity. We previously reported that CRTC1 deficiency in melanocortin‐4 receptor (MC4R)‐expressing neurons, which regulate appetite and energy metabolism in the brain, causes hyperphagia and obesity under a high‐fat diet (HFD). HFD is preferred for mice, and the dietary fat in HFD is the main factor contributing to its palatability. These findings, along with our previous results, suggest that CRTC1 regulates the appetite for dietary fat. Therefore, in this study, we aimed to investigate the dietary fat intake behavior and energy metabolism of MC4R neuron‐specific CRTC1 knockout mice fed soybean oil or lard. CRTC1 deficiency increased the intake of soybean oil and significantly increased body weight gain. Furthermore, obesity induced by soybean oil intake was partially due to leptin resistance. No significant changes in soybean oil intake were observed between young CRTC1‐deficient and wild‐type mice; however, soybean oil intake increased with age. Moreover, lard intake did not significantly affect the body weight. Overall, our findings highlighted the crucial role of CRTC1 in the regulation of spontaneous dietary fat intake. Furthermore, the role of CRTC1 becomes increasingly significant with age. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Modulation of Ca2+ oscillation following ischemia and nicotinic acetylcholine receptors in primary cortical neurons by high-throughput analysis.

Author

Sasaki, Tsutomu, Hisada, Sunao, Kanki, Hideaki, Nunomura, Kazuto, Lin, Bangzhong, Nishiyama, Kumiko, Kawano, Tomohito, Matsumura, Shigenobu, and Mochizuki, Hideki

Subjects
*NICOTINIC acetylcholine receptors, *FREQUENCIES of oscillating systems, *NEURON analysis, *CEREBRAL ischemia, *METHYL aspartate receptors, *NICOTINIC receptors
Abstract

Calcium oscillations in primary neuronal cultures and iPSCs have been employed to investigate arrhythmogenicity and epileptogenicity in drug development. Previous studies have demonstrated that Ca2+ influx via NMDA and nicotinic acetylcholine receptors (nAChRs) modulates Ca2+ oscillations. Nevertheless, there has been no comprehensive investigation into the impact of ischemia or nAChR-positive allosteric modulators (PAM) drugs on Ca2+ oscillations at a level that would facilitate high-throughput screening. We investigated the effects of ischemia and nAChR subtypes or nAChR PAM agonists on Ca2+ oscillations in high-density 2D and 3D-sphere primary neuronal cultures using 384-well plates with FDSS-7000. Ischemia for 1 and 2 h resulted in an increase in the frequency of Ca2+ oscillations and a decrease in their amplitude in a time-dependent manner. The NMDA and AMPA receptor inhibition significantly suppressed Ca2+ oscillation. Inhibition of NR2A or NR2B had the opposite effect on Ca oscillations. The potentiation of ischemia-induced Ca2+ oscillations was significantly inhibited by the NMDA receptor antagonist, MK-801, and the frequency of these oscillations was suppressed by the NR2B inhibitor, Ro-256981. In the 3D-neurosphere, the application of an α7nAChR agonist increased the frequency of Ca2+ oscillations, whereas the activation of α4β2 had no effect. The combination of nicotine and PNU-120596 (type II PAM) affected the frequency and amplitude of Ca2+ oscillations in a manner distinct from that of type I PAM. These systems may be useful not only for detecting epileptogenicity but also in the search for neuroprotective agents against cerebral ischemia. [ABSTRACT FROM AUTHOR]

Published
2024
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18. The PDK1-FoxO1 signaling in adipocytes controls systemic insulin sensitivity through the 5-lipoxygenase–leukotriene B₄ axis

Author

Hosooka, Tetsuya, Hosokawa, Yusei, Matsugi, Kaku, Shinohara, Masakazu, Senga, Yoko, Tamori, Yoshikazu, Aoki, Chikako, Matsui, Sho, Sasaki, Tsutomu, Kitamura, Tadahiro, Kuroda, Masashi, Sakaue, Hiroshi, Nomura, Kazuhiro, Yoshino, Kei, Nabatame, Yuko, Itoh, Yoshito, Yamaguchi, Kanji, Hayashi, Yoshitake, Nakae, Jun, Accili, Domenico, Yokomizo, Takehiko, Seino, Susumu, Kasuga, Masato, and Ogawa, Wataru

Published
2020

22. Mechanical thrombectomy in acute ischemic stroke patients with left ventricular assist device

Author

Kitano, Takaya, Sakaguchi, Manabu, Yamagami, Hiroshi, Ishikawa, Tatsuya, Ishibashi-Ueda, Hatsue, Tanaka, Kanta, Okazaki, Shuhei, Sasaki, Tsutomu, Kadono, Yoshinori, Takagaki, Masatoshi, Nishida, Takeo, Nakamura, Hajime, Yanase, Masanobu, Fukushima, Norihide, Shiozawa, Masayuki, Toyoda, Kazunori, Takahashi, Jun C., Funatsu, Takayuki, Ryu, Bikei, Yoshioka, Daisuke, Toda, Koichi, Murayama, Shigeo, Kawamata, Takakazu, Kishima, Haruhiko, Sawa, Yoshiki, Mochizuki, Hideki, and Todo, Kenichi

Published
2020
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28. microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity

Author

Horie, Takahiro, Nakao, Tetsushi, Miyasaka, Yui, Nishino, Tomohiro, Matsumura, Shigenobu, Nakazeki, Fumiko, Ide, Yuya, Kimura, Masahiro, Tsuji, Shuhei, Rodriguez, Randolph Ruiz, Watanabe, Toshimitsu, Yamasaki, Tomohiro, Xu, Sijia, Otani, Chiharu, Miyagawa, Sawa, Matsushita, Kazuki, Sowa, Naoya, Omori, Aoi, Tanaka, Jin, Nishimura, Chika, Nishiga, Masataka, Kuwabara, Yasuhide, Baba, Osamu, Watanabe, Shin, Nishi, Hitoo, Nakashima, Yasuhiro, Picciotto, Marina R., Inoue, Haruhisa, Watanabe, Dai, Nakamura, Kazuhiro, Sasaki, Tsutomu, Kimura, Takeshi, and Ono, Koh

Published
2021
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31. Medium-chain triglyceride-specific appetite is regulated by the β-oxidation of medium-chain fatty acids in the liver.

Author

Maruyama, Tsugunori, Matsui, Sho, Kobayashi, Ryosuke, Horii, Takuro, Oguri, Yasuo, Tsuzuki, Satoshi, Horie, Takahiro, Ono, Koh, Hatada, Izuho, and Sasaki, Tsutomu

Subjects
HYPOTHALAMUS, APPETITE, CORN oil, GALANIN, TRIGLYCERIDES, ACYL coenzyme A
Abstract

Most studies on fat appetite have focused on long-chain triglycerides (LCTs) due to their obesogenic properties. Medium-chain triglycerides (MCTs), conversely, exhibit antiobesogenic effects; however, the regulation of MCT intake remains elusive. Here, we demonstrate that mice can distinguish between MCTs and LCTs, and the specific appetite for MCTs is governed by hepatic β-oxidation. We generated liver-specific medium-chain acyl-CoA dehydrogenase (MCAD)-deficient (MCADL−/−) mice and analyzed their preference for MCT and LCT solutions using glyceryl trioctanoate (C8-TG), glyceryl tridecanoate (C10-TG), corn oil, and lard oil in two-bottle choice tests conducted over 8 days. In addition, we used lick microstructure analyses to evaluate the palatability and appetite for MCT and LCT solutions. Finally, we measured the expression levels of genes associated with fat ingestion (Galanin, Qrfp, and Nmu) in the hypothalamus 2 h after oral gavage of fat. Compared with control mice, MCADL−/− mice exhibited a significantly reduced preference for MCT solutions, with no alteration in the preference for LCTs. Lick analysis revealed that MCADL−/− mice displayed a significantly decreased appetite for MCT solutions only while the palatability of both MCT and LCT solutions remained unaffected. Hypothalamic Galanin expression in control mice was elevated by oral gavage of C8-TG but not by LCTs, and this response was abrogated in MCADL−/− mice. In summary, our data suggest that hepatic β-oxidation is required for MCT-specific appetite but not for LCT-specific appetite. The induction of hypothalamic galanin upon MCT ingestion, dependent on hepatic β-oxidation, could be involved in the regulation of MCT-specific appetite. NEW & NOTEWORTHY: Whether and how medium-chain triglyceride (MCT) intake is regulated remains unknown. Here, we showed that mice can discriminate between MCTs and LCTs. Hepatic β-oxidation participates in MCT-specific appetite, and hypothalamic galanin may be one of the factors that regulate MCT intake. Because of the antiobesity effects of MCTs, studying MCT-specific appetite may help combat obesity by promoting the intake of MCTs instead of LCTs. [ABSTRACT FROM AUTHOR]

Published
2024
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34. Carnosol suppresses interleukin-6 production in mouse lungs injured by ischemia-reperfusion operation and in RAW264.7 macrophages treated with lipopolysaccharide

Author

Momozane, Toru, Kawamura, Tomohiro, Itoh, Yumi, Sanosaka, Masato, Sasaki, Tsutomu, Kanzaki, Ryu, Ose, Naoko, Funaki, Soichiro, Shintani, Yasushi, Minami, Masato, Okumura, Meinoshin, and Takemori, Hiroshi

Subjects
Interleukins -- Health aspects, Lung -- Health aspects, Lipopolysaccharides -- Health aspects, Biological sciences
Abstract

Carnosol is a naturally occurring herbal compound, known for its antioxidative properties. We previously found that carnosol protected mouse lungs from ischemia-reperfusion injury in ex vivo cultures. To elucidate the molecular mechanisms underpinning carnosol-mediated lung protection, we analyzed modes of interleukin-6 (IL-6) gene expression, which is associated with lung ischemia-reperfusion injury. Microarray analysis of mouse lungs suggested that IL-6 mRNA levels were elevated in the mouse lungs subjected to clamp-reperfusion, which was associated with elevated levels of other inflammatory modulators, such as activating transcription factor 3 (ATF3). Carnosol pretreatment lowered the IL-6 protein levels in mouse lung homogenates prepared after the clamp-reperfusion. On the other hand, the ATF3 gene expression was negatively correlated with that of IL-6 in RAW264.7 cells. IL-6 mRNA levels and gene promoter activities were suppressed by carnosol in RAW264.7 cells, but rescued by ATF3 knockdown. When RAW264.7 cells were subjected to hypoxia-reoxygenation, carnosol treatment lowered oxygen consumption after reoxygenation, which was coupled with a correlation with a transient production of mitochondrial reactive oxygen species and following ATF3 gene expression. These results suggest that carnosol treatment could be a new strategy for protecting lungs from ischemia-reperfusion injury by modulating the ATF3-IL-6 axis.Key words: carnosol, IL-6, ATF3, lung ischemia-reperfusion injury.Le carnosol est un compose naturel d'origine vegetale connu pour ses proprietes antioxydantes. Les auteurs avaient precedemment trouve que le carnosol protegeait le poumon de la souris du dommage d'ischemie-reperfiision en culture ex vivo. Afin d'elucider les mecanismes moleculaires qui sous-tendent la protection du poumon par le carnosol, ils ont analyse l'expression genique de l'interleukine-6 (IL-6), associee au dommage d'ischemie-reperfusion pulmonaire. Une analyse sur microreseau de poumons de souris a revele que les niveaux de l'ARNm d'IL-6 etaient eleves dans les poumons des souris soumises a un clamp-reperfusion, qui etaient associes a des niveaux eleves d'autres modulateurs inflammatoires tels que le facteur ATF3 (pour << activating transcription factor 3 >>). Un pretraitement au carnosol diminuait les niveaux proteiques d'IL-6 dans des homogenats de poumons prepares apres le clamp-reperfusion. Par contre, l'expression genique d'ATF3 etait correlee negativement avec celle de l'IL-6 chez les cellules RAW264.7. Les niveaux d'ARNm d'IL-6 et l'activite du promoteur du gene etaient diminues par le carnosol dans les cellules RAW264.7, mais retablis par le knock-down d'ATF3. Lorsque les cellules RAW264.7 etaient soumises a une hypoxie-reoxygenation, le traitement au carnosol diminuait la consommation d'oxygene apres la reoxygenation, diminution couplee a une production transitoire de derives reactifs d'oxygene mitochondriaux a la suite de l'expression d'ATF3. Ces resultats suggerent que le traitement au carnosol pourrait constituer une nouvelle strategie de protection des poumons des dommages d'ischemie-reperfusion en modulant l'axe ATF3-IL-6. [Traduit par la Redaction]Mots-cles: carnosol, IL-6, ATF3, dommage pulmonaire d'ischemie-reperfusion., IntroductionInflammatory cytokines play important roles in the development of tissue injury after ischemia-reperfusion (Beckers et al. 2017). Proper control of inflammatory signals is considered an excellent prognosis in surgery for [...]

Published
2018
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45. Hypothalamic SIRT1 prevents age-associated weight gain by improving leptin sensitivity in mice

Author

Sasaki, Tsutomu, Kikuchi, Osamu, Shimpuku, Mayumi, Susanti, Vina Yanti, Yokota-Hashimoto, Hiromi, Taguchi, Ryo, Shibusawa, Nobuyuki, Sato, Takashi, Tang, Lijun, Amano, Kosuke, Kitazumi, Tomoya, Kuroko, Mitsutaka, Fujita, Yuki, Maruyama, Jun, Lee, Yong-soo, Kobayashi, Masaki, Nakagawa, Takashi, Minokoshi, Yasuhiko, Harada, Akihiro, Yamada, Masanobu, and Kitamura, Tadahiro

Published
2014
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46. Impact of stroke on survival in patients with cancer.

Author

Gon, Yasufumi, Sasaki, Tsutomu, Kawano, Tomohiro, Okazaki, Shuhei, Todo, Kenichi, Takeda, Toshihiro, Matsumura, Yasushi, and Mochizuki, Hideki

Subjects
*OVERALL survival, *STROKE patients, *CANCER patients, *TUMOR classification
Abstract

[Display omitted] [ABSTRACT FROM AUTHOR]

Published
2023
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