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Article: Nocturnal melatonin increases glucose uptake via insulin-independent action in the goldfish brain.

Watanabe, Kazuki / Nakano, Masaki / Maruyama, Yusuke / Hirayama, Jun / Suzuki, Nobuo / Hattori, Atsuhiko

2023 Volume 14, Page(s) 1173113

Abstract: Melatonin, a neurohormone nocturnally produced by the pineal gland, is known to regulate the circadian rhythm. It has been recently reported that variants of melatonin receptors are associated with an increased risk of hyperglycemia and type 2 diabetes, ... ...

Abstract	Melatonin, a neurohormone nocturnally produced by the pineal gland, is known to regulate the circadian rhythm. It has been recently reported that variants of melatonin receptors are associated with an increased risk of hyperglycemia and type 2 diabetes, suggesting that melatonin may be involved in the regulation of glucose homeostasis. Insulin is a key hormone that regulates circulating glucose levels and cellular metabolism after food intake in many tissues, including the brain. Although cells actively uptake glucose even during sleep and without food, little is known regarding the physiological effects of nocturnal melatonin on glucose homeostasis. Therefore, we presume the involvement of melatonin in the diurnal rhythm of glucose metabolism, independent of insulin action after food intake. In the present study, goldfish (
MeSH term(s)	Animals ; Melatonin/metabolism ; Goldfish/physiology ; Diabetes Mellitus, Type 2 ; Glucose/metabolism ; Brain/metabolism
Chemical Substances	Melatonin (JL5DK93RCL) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2023-05-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1173113
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Article ; Online: N1-Acetyl-5-methoxykynuramine, which decreases in the hippocampus with aging, improves long-term memory via CaMKII/CREB phosphorylation.

Watanabe, Kazuki / Maruyama, Yusuke / Iwashita, Hikaru / Kato, Haruyasu / Hirayama, Jun / Hattori, Atsuhiko

Journal of pineal research

2023 Volume 76, Issue 1, Page(s) e12934

Abstract: Melatonin is a molecule ubiquitous in nature and involved in several physiological functions. In the brain, melatonin is converted to N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and then to N1-acetyl-5-methoxykynuramine (AMK), which has been reported ... ...

Abstract	Melatonin is a molecule ubiquitous in nature and involved in several physiological functions. In the brain, melatonin is converted to N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and then to N1-acetyl-5-methoxykynuramine (AMK), which has been reported to strongly enhance long-term object memory formation. However, the synthesis of AMK in brain tissues and the underlying mechanisms regarding memory formation remain largely unknown. In the present study, young and old individuals from a melatonin-producing strain, C3H/He mice, were employed. The amount of AMK in the pineal gland and plasma was very low compared with those of melatonin at night; conversely, in the hippocampus, the amount of AMK was higher than that of melatonin. Indoleamine 2, 3-dioxygenase (Ido) mRNA was expressed in multiple brain tissues, whereas tryptophan 2,3-dioxygenase (Tdo) mRNA was expressed only in the hippocampus, and its lysate had melatonin to AFMK conversion activity, which was blocked by the TDO inhibitor. The expression levels of phosphorylated cAMP response element binding protein (CREB) and PSD-95 in whole hippocampal tissue were significantly increased with AMK treatment. Before increasing in the whole tissue, CREB phosphorylation was significantly enhanced in the nuclear fraction. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found that downregulated genes in hippocampus of old C3H/He mice were more enriched for long-term potentiation (LTP) pathway. Gene set enrichment analysis showed that LTP and neuroactive receptor interaction gene sets were enriched in hippocampus of old mice. In addition, Ido1 and Tdo mRNA expression was significantly decreased in the hippocampus of old mice compared with young mice, and the decrease in Tdo mRNA was more pronounced than Ido1. Furthermore, there was a higher decrease in AMK levels, which was less than 1/10 that of young mice, than in melatonin levels in the hippocampus of old mice. In conclusion, we first demonstrated the Tdo-related melatonin to AMK metabolism in the hippocampus and suggest a novel mechanism of AMK involved in LTP and memory formation. These results support AMK as a potential therapeutic agent to prevent memory decline.
MeSH term(s)	Mice ; Animals ; Melatonin/metabolism ; Cyclic AMP Response Element-Binding Protein/metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism ; Phosphorylation ; Mice, Inbred C3H ; Kynuramine/metabolism ; Aging ; Hippocampus/metabolism ; RNA, Messenger/metabolism
Chemical Substances	Melatonin (JL5DK93RCL) ; Cyclic AMP Response Element-Binding Protein ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 (EC 2.7.11.17) ; N-acetyl-N-formyl-5-methoxykynurenamine (52450-38-1) ; Kynuramine (363-36-0) ; RNA, Messenger
Language	English
Publishing date	2023-12-12
Publishing country	England
Document type	Journal Article
ZDB-ID	632697-3
ISSN	1600-079X ; 0742-3098
ISSN (online)	1600-079X
ISSN	0742-3098
DOI	10.1111/jpi.12934
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Article ; Online: Abdominal breathing manoeuvre reduces passive drag acting on gliding swimmers.

Maruyama, Yusuke / Yanai, Toshimasa

Sports biomechanics

2017 Volume 14, Issue 4, Page(s) 413–423

Abstract: The purpose of this study was to test the hypothesis that the passive drag acting on a gliding swimmer is reduced if the swimmer adopts an abdominal breathing manoeuvre (expanding the abdominal wall) rather than chest breathing manoeuvre (expanding the ... ...

Abstract	The purpose of this study was to test the hypothesis that the passive drag acting on a gliding swimmer is reduced if the swimmer adopts an abdominal breathing manoeuvre (expanding the abdominal wall) rather than chest breathing manoeuvre (expanding the rib cage). Eleven male participants participated in this study. A specialised towing machine was used to tow each participant with tension set at various magnitudes and to record time series data of towing velocity. Participants were asked to inhale air by expanding the abdominal wall or the rib cage and to maintain the same body configuration throughout gliding. The steady-state velocity was measured and the coefficient of drag was calculated for each towing trial to compare between the breathing manoeuvres. The results showed that the towing velocity was increased by 0.02 m/s with a towing force of 34.3 N and by 0.06 m/s with a towing force of 98.1 N. The coefficient of drag was reduced by 5% with the abdominal breathing manoeuvre, which was found to be statistically significant (p < 0.05). These results indicate that adopting the abdominal breathing manoeuvre during gliding reduces the passive drag and the hypothesis was supported.
MeSH term(s)	Adult ; Biomechanical Phenomena/physiology ; Humans ; Male ; Posture/physiology ; Respiratory Mechanics/physiology ; Swimming/physiology ; Young Adult
Language	English
Publishing date	2017-02-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1752-6116
ISSN (online)	1752-6116
DOI	10.1080/14763141.2015.1084030
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Article ; Online: Dietary melatonin and liver cancer incidence in Japan: From the Takayama study.

Wada, Keiko / Hattori, Atsuhiko / Maruyama, Yusuke / Mori, Tomoka / Sugino, Masaaki / Nakashima, Yuma / Yamakawa, Michiyo / Yamamoto, Masayuki / Hori, Akihiro / Seishima, Mitsuru / Tanabashi, Shinobu / Matsushita, Shogen / Nagata, Chisato

Cancer science

2024

Abstract: There is some biological plausibility that exogenous melatonin plays a role in preventing liver carcinogenesis. There has been little research on the association between melatonin intake in a normal diet and health outcomes. We evaluated the association ... ...

Abstract	There is some biological plausibility that exogenous melatonin plays a role in preventing liver carcinogenesis. There has been little research on the association between melatonin intake in a normal diet and health outcomes. We evaluated the association between dietary melatonin intake and the incidence of liver cancer in a population-based prospective study in Japan. This study included 30,824 residents of Takayama city who were 35 years of age or older in 1992 and had participated in the Takayama study, Japan. Dietary intake was assessed using a validated food frequency questionnaire at the baseline. Melatonin content in foods was measured by liquid chromatography-tandem mass spectrometry. Cancer incidence was confirmed through regional population-based cancer registries in Gifu. Liver cancer was defined as code C22 according to the International Classification of Diseases and Related Health Problems, 10th Revision. Hazard ratios for liver cancer were estimated for the tertile groups of melatonin intake using a Cox proportional hazards model. During the mean follow-up period of 13.6 years, 189 individuals developed liver cancer. Compared with subjects in the lowest tertile of melatonin intake, those in the middle and highest tertiles had decreased risks of liver cancer, with a significant linear trend after multivariate adjustments (hazard ratios: 0.64 and 0.65, respectively, trend p = 0.023). There was no significant interaction by sex (interaction p = 0.54). This initial finding, which needs to be confirmed by further studies, suggests that consuming melatonin-containing foods might play a role in the prevention of liver cancer.
Language	English
Publishing date	2024-02-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2115647-5
ISSN	1349-7006 ; 1349-7006
ISSN (online)	1349-7006
ISSN	1349-7006
DOI	10.1111/cas.16103
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Article ; Online: All-trans retinoic acid induces lipophagy through the activation of the AMPK-Beclin1 signaling pathway and reduces Rubicon expression in adipocytes.

Mori, Yuki / Masuda, Masashi / Yoshida-Shimizu, Risa / Aoyagi, Saki / Adachi, Yuichiro / Nguyen, Anh The / Maruyama, Yusuke / Okumura, Yosuke / Kamei, Yuki / Sakai, Maiko / Ohnishi, Kohta / Ohminami, Hirokazu / Taketani, Yutaka

The Journal of nutritional biochemistry

2024 Volume 126, Page(s) 109589

Abstract: Lipophagy is defined as a lipolysis pathway that degrades lipid droplet (LD) via autophagy. All-trans retinoic acid (atRA), a metabolite of vitamin A, stimulates lipolysis through hormone-sensitive lipase and β-oxidation. However, the regulation of ... ...

Abstract	Lipophagy is defined as a lipolysis pathway that degrades lipid droplet (LD) via autophagy. All-trans retinoic acid (atRA), a metabolite of vitamin A, stimulates lipolysis through hormone-sensitive lipase and β-oxidation. However, the regulation of lipolysis by atRA-induced autophagy in adipocytes remains unclear. In this study, we investigated the effect of atRA on autophagy in epididymal fat of mice and the molecular mechanisms of autophagy in 3T3-L1 adipocytes. Western blotting showed that atRA decreased the expression of p62, a cargo receptor for autophagic degradation, and increased the expression of the lipidated LC3B (LC3B-II), an autophagy marker, in epididymal fat. Next, we confirmed that atRA increased autophagic flux in differentiated 3T3-L1 cells using the GFP-LC3-RFP-LC3ΔG probe. Immunofluorescent staining revealed that the colocalization of LC3B with perilipin increased in differentiated 3T3-L1 cells treated with atRA. The knockdown of Atg5, an essential gene in autophagy induction, partly suppressed the atRA-induced release of non-esterified fatty acid (NEFA) from LDs in differentiated 3T3-L1 cells. atRA time-dependently elicited the phosphorylation of AMPK and Beclin1, autophagy-inducing factors, in mature 3T3-L1 adipocytes. Inversely, atRA decreased the protein expression of Rubicon, an autophagy repressor, in differentiated 3T3-L1 cells and epididymal fat. Interestingly, the expression of ALDH1A1, atRA-synthesizing enzymes, increased in epididymal fat with decreased protein expression of Rubicon in aged mice. These results suggest that atRA may partially induce lipolysis through lipophagy by activating the AMPK-Beclin1 signaling pathway in the adipocytes and increased atRA levels may contribute to decreased Rubicon expression in the epididymal fat of aged mice. (248/250 words).
MeSH term(s)	Mice ; Animals ; AMP-Activated Protein Kinases/genetics ; AMP-Activated Protein Kinases/metabolism ; Beclin-1/genetics ; Beclin-1/metabolism ; Signal Transduction ; Lipolysis ; Tretinoin/pharmacology ; Tretinoin/metabolism ; Autophagy ; Adipocytes ; 3T3-L1 Cells
Chemical Substances	AMP-Activated Protein Kinases (EC 2.7.11.31) ; Beclin-1 ; Tretinoin (5688UTC01R)
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1014929-6
ISSN	1873-4847 ; 0955-2863
ISSN (online)	1873-4847
ISSN	0955-2863
DOI	10.1016/j.jnutbio.2024.109589
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Book ; Online: Neural Network Training With Homomorphic Encryption

Mihara, Kentaro / Yamaguchi, Ryohei / Mitsuishi, Miguel / Maruyama, Yusuke

2020

Abstract: We introduce a novel method and implementation architecture to train neural networks which preserves the confidentiality of both the model and the data. Our method relies on homomorphic capability of lattice based encryption scheme. Our procedure is ... ...

Abstract	We introduce a novel method and implementation architecture to train neural networks which preserves the confidentiality of both the model and the data. Our method relies on homomorphic capability of lattice based encryption scheme. Our procedure is optimized for operations on packed ciphertexts in order to achieve efficient updates of the model parameters. Our method achieves a significant reduction of computations due to our way to perform multiplications and rotations on packed ciphertexts from a feedforward network to a back-propagation network. To verify the accuracy of the training model as well as the implementation feasibility, we tested our method on the Iris data set by using the CKKS scheme with Microsoft SEAL as a back end. Although our test implementation is for simple neural network training, we believe our basic implementation block can help the further applications for more complex neural network based use cases.
Keywords	Computer Science - Cryptography and Security
Subject code	000
Publishing date	2020-12-25
Publishing country	us
Document type	Book ; Online
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Article ; Online: The melatonin metabolite N1-acetyl-5-methoxykynuramine facilitates long-term object memory in young and aging mice.

Iwashita, Hikaru / Matsumoto, Yukihisa / Maruyama, Yusuke / Watanabe, Kazuki / Chiba, Atsuhiko / Hattori, Atsuhiko

Journal of pineal research

2020 Volume 70, Issue 1, Page(s) e12703

Abstract: Melatonin (MEL) has been reported to enhance cognitive processes, making it a potential treatment for cognitive decline. However, the role of MEL's metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in ... ...

Abstract	Melatonin (MEL) has been reported to enhance cognitive processes, making it a potential treatment for cognitive decline. However, the role of MEL's metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in these effects are unknown. The current study directly investigated the acute effects of systemic MEL, AFMK, and AMK on novel object recognition. We also analyzed MEL, AFMK, and AMK levels in hippocampus and temporal lobe containing the perirhinal cortex following systemic MEL and AMK treatment. AMK administered post-training had a more potent effect on object memory than MEL and AFMK. AMK was also able to rescue age-associated declines in memory impairments when object memory was tested up to 4 days following training. Results from administering AMK at varying times around the training trial and the metabolism time course in brain tissue suggest that AMK's memory-enhancing effects reflect memory consolidation. Furthermore, inhibiting the MEL-to-AMK metabolic pathway disrupted object memory at 24 hours post-training, suggesting that endogenous AMK might play an important role in long-term memory formation. This is the first study to report that AMK facilitates long-term object memory performance in mice, and that MEL crosses the blood-brain barrier and is immediately converted to AMK in brain tissue. Overall, these results support AMK as a potential therapeutic agent to improve or prevent memory decline.
MeSH term(s)	Age Factors ; Animals ; Behavior, Animal/drug effects ; Biotransformation ; Hippocampus/drug effects ; Hippocampus/metabolism ; Kynuramine/analogs & derivatives ; Kynuramine/metabolism ; Kynuramine/pharmacology ; Male ; Melatonin/deficiency ; Melatonin/genetics ; Melatonin/pharmacology ; Memory, Long-Term/drug effects ; Mice, Inbred ICR ; Open Field Test ; Temporal Lobe/drug effects ; Temporal Lobe/metabolism ; Time Factors ; Mice
Chemical Substances	Kynuramine (363-36-0) ; N-acetyl-N-formyl-5-methoxykynurenamine (52450-38-1) ; N-acetyl-5-methoxy kynurenamine (52450-39-2) ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2020-11-20
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	632697-3
ISSN	1600-079X ; 0742-3098
ISSN (online)	1600-079X
ISSN	0742-3098
DOI	10.1111/jpi.12703
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Article ; Online: Antioxidants restore store-operated Ca

Sakai-Takemura, Fusako / Saito, Fumiaki / Nogami, Ken'ichiro / Maruyama, Yusuke / Elhussieny, Ahmed / Matsumura, Kiichiro / Takeda, Shin'ichi / Aoki, Yoshitsugu / Miyagoe-Suzuki, Yuko

FASEB bioAdvances

2023 Volume 5, Issue 11, Page(s) 453–469

Abstract: Store-operated ... ...

Abstract	Store-operated Ca
Language	English
Publishing date	2023-10-26
Publishing country	United States
Document type	Journal Article
ISSN	2573-9832
ISSN (online)	2573-9832
DOI	10.1096/fba.2023-00069
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Article ; Online: Mesenchymal stem cells derived from human induced pluripotent stem cells improve the engraftment of myogenic cells by secreting urokinase-type plasminogen activator receptor (uPAR).

Elhussieny, Ahmed / Nogami, Ken'ichiro / Sakai-Takemura, Fusako / Maruyama, Yusuke / Takemura, Natsumi / Soliman, Wael Talaat / Takeda, Shin'ichi / Miyagoe-Suzuki, Yuko

Stem cell research & therapy

2021 Volume 12, Issue 1, Page(s) 532

Abstract: Background: Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disease caused by mutations in the dystrophin gene. Transplantation of myogenic stem cells holds great promise for treating muscular dystrophies. However, poor engraftment of ... ...

Abstract	Background: Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disease caused by mutations in the dystrophin gene. Transplantation of myogenic stem cells holds great promise for treating muscular dystrophies. However, poor engraftment of myogenic stem cells limits the therapeutic effects of cell therapy. Mesenchymal stem cells (MSCs) have been reported to secrete soluble factors necessary for skeletal muscle growth and regeneration. Methods: We induced MSC-like cells (iMSCs) from induced pluripotent stem cells (iPSCs) and examined the effects of iMSCs on the proliferation and differentiation of human myogenic cells and on the engraftment of human myogenic cells in the tibialis anterior (TA) muscle of NSG-mdx Results: iMSCs promoted the proliferation and differentiation of human myogenic cells to the same extent as bone marrow-derived (BM)-MSCs in coculture experiments. In cell transplantation experiments, iMSCs significantly improved the engraftment of human myogenic cells injected into the TA muscle of NSG-mdx Conclusions: Our results indicate that iMSCs are a new tool to improve the engraftment of myogenic progenitors in dystrophic muscle.
MeSH term(s)	Animals ; Cell Differentiation ; Dystrophin/genetics ; Humans ; Induced Pluripotent Stem Cells ; Mesenchymal Stem Cells ; Mice ; Mice, Inbred NOD ; Mice, Inbred mdx ; Muscle, Skeletal ; Muscular Dystrophy, Duchenne/genetics ; Muscular Dystrophy, Duchenne/therapy ; Receptors, Urokinase Plasminogen Activator/genetics
Chemical Substances	Dystrophin ; Receptors, Urokinase Plasminogen Activator
Language	English
Publishing date	2021-10-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-021-02594-1
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Article ; Online: Associations Between Dietary Melatonin Intake and Total and Cause-Specific Mortality Among Japanese Adults in the Takayama Study.

Nagata, Chisato / Wada, Keiko / Yamakawa, Michiyo / Nakashima, Yuma / Koda, Sachi / Uji, Takahiro / Onuma, Sakiko / Oba, Shino / Maruyama, Yusuke / Hattori, Atsuhiko

American journal of epidemiology

2021 Volume 190, Issue 12, Page(s) 2639–2646

Abstract: Potential health benefits of melatonin have been suggested. Although melatonin is present in various foods, little is known about the health effects of dietary melatonin intake. We estimated habitual dietary melatonin intake and examined its association ... ...

Abstract	Potential health benefits of melatonin have been suggested. Although melatonin is present in various foods, little is known about the health effects of dietary melatonin intake. We estimated habitual dietary melatonin intake and examined its association with total and cause-specific mortality in a population-based cohort study in Japan. Study subjects included 13,355 men and 15,724 women aged ≥35 years who responded to a self-administered questionnaire in 1992. Their diets were assessed via a food frequency questionnaire at baseline. The melatonin content in various foods on the questionnaire was measured to estimate melatonin intake. Mortality was ascertained during 16 years of follow-up (1992-2008). Hazard ratios (HRs) and 95% confidence intervals (CIs) for total and cause-specific mortality were calculated according to melatonin quartiles. A total of 5,339 deaths occurred during follow-up. Melatonin intake was significantly associated with decreased risks of total mortality, cardiovascular mortality, and noncancer, noncardiovascular mortality after controlling for covariates; HRs for the highest quartile of melatonin intake versus the lowest were 0.90 (95% CI: 0.82, 0.98; P for trend = 0.05), 0.85 (95% CI: 0.72, 0.99; P for trend = 0.10), and 0.77 (95% CI: 0.67, 0.90; P for trend = 0.003), respectively. The data suggest a potential benefit of dietary melatonin with regard to mortality rates.
MeSH term(s)	Adult ; Aged ; Cause of Death/trends ; Diet/statistics & numerical data ; Eating ; Female ; Humans ; Japan/epidemiology ; Male ; Melatonin/administration & dosage ; Middle Aged ; Mortality/trends ; Prospective Studies ; Sleep ; Sociodemographic Factors
Chemical Substances	Melatonin (JL5DK93RCL)
Language	English
Publishing date	2021-08-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2937-3
ISSN	1476-6256 ; 0002-9262
ISSN (online)	1476-6256
ISSN	0002-9262
DOI	10.1093/aje/kwab213
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