Tsukushi is essential for the development of the inner ear

Miwa, Toru; Ohta, Kunimasa; Ito, Naofumi; Miyakawa, Tsuyoshi; Tanaka, Takeo; Nakagata, Naomi; Song, Wen Jie; Minoda, Ryosei

doi:10.1186/s13041-020-00570-z

Cited by 15 publications

(24 citation statements)

References 43 publications

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“…The numbers of outer hair cells (OHC) and inner hair cells (IHC) in a 140-μm basal segment of the basilar membrane were calculated in each group. Only the hair cells with an intact stereocilia bundle and a cuticular plate were counted in every turn of the cochlea as per previously described methods (Miwa et al, 2020 ). A second researcher confirmed the accuracy of the measurements.…”

Section: Methodsmentioning

confidence: 99%

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Protective Effects of N1-Methylnicotinamide Against High-Fat Diet- and Age-Induced Hearing Loss via Moderate Overexpression of Sirtuin 1 Protein

Miwa

2021

Front. Cell. Neurosci.

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Age-related hearing loss (ARHL) is the most common form of hearing loss and the predominant neurodegenerative disease associated with aging. Sirtuin 1 (SIRT1) is associated with the most complex physiological processes, including metabolism, cancer onset, and aging. SIRT1 protein levels are enhanced by the conversion of nicotinamide to N1-methylnicotinamide (MNAM), independent of its mRNA levels. Moreover, MNAM has implications in increased longevity achieved through its mitohormetic effects. Nicotinamide N-methyltransferase (Nnmt) is an enzyme involved in MNAM metabolism, and its level increases under caloric restriction (CR) conditions. The CR condition has implications in delaying ARHL onset. In this study, we aimed to determine the relationship between diet, hearing function, SIRT1 and SIRT3 expression levels in the inner ear, and cochlear morphology. Mice fed with a high-fat diet (HFD), HFD + 1% MNAM, and low-fat diet (LFD) were monitored for age-related auditory-evoked brainstem responses, and changes in cochlear histology, metabolism, and protein and mRNA expressions were analyzed. Our results revealed that the HFD- and aging-mediated downregulated expression of SIRT1 and SIRT3 promoted hearing loss that was obfuscated by MNAM supplementation-induced upregulated expression of cochlear SIRT1 and SIRT3. Thus, our results suggest that MNAM can be used as a therapeutic agent for preventing ARHL.

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Section: Methodsmentioning

confidence: 99%

“…The average thickness of the stria vascularis was measured by analyzing the images of the sections containing the midmodiolar region using the ImageJ software (NIH) as per previously described methods (Miwa et al, 2019 , 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Protective Effects of N1-Methylnicotinamide Against High-Fat Diet- and Age-Induced Hearing Loss via Moderate Overexpression of Sirtuin 1 Protein

Miwa

2021

Front. Cell. Neurosci.

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“…Gestationswoche nur noch auf die Haarsinneszellen begrenzt [57]. Aktuelle Studien zeigen, dass insbesondere auch Proteoglykane der extrazellulären Matrix an der Entwicklung der Haarsinneszellen und Spiralganglienneurone beteiligt sind, indem sie bestimmte Gene hoch-oder runterregulieren [58].…”

Section: Glykogenablagerung Inunclassified

Embryologie, Fehlbildungen und seltene Erkrankungen der Cochlea

Warnecke

Giesemann

2021

Laryngorhinootologie

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ZusammenfassungAuch wenn die einzelnen Krankheitsbilder selten sind, stellen seltene Erkrankungen der Cochlea in ihrer Gänze eine doch gehäufte Entität dar, die zu Hörstörungen führt. Ein/Das Ziel des vorliegenden Referates war es, unter Berücksichtigung der Embryonalentwicklung der Hörschnecke und einer systematischen Zusammenfassung eine übersichtliche Darstellung der seltenen cochleären Erkrankungen zu ermöglichen. Auch wenn rapide biotechnologische und bioinformatische Fortschritte die Diagnose einer seltenen Erkrankung erleichtern, so kann oft nur im interdisziplinären Austausch der Verdacht einer seltenen Erkrankung erhoben werden. Trotz gleicher zugrunde liegender Mutationen kann der Phänotyp nicht nur bei den genetisch bedingten Hörstörungen sondern auch bei den syndromalen Erkrankungen stark variieren. Schließlich wird deutlich, dass der Phänotyp der einzelnen seltenen Erkrankungen nicht ausschließlich durch die klassische Genetik bestimmt werden kann.

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“…Recently, Tsukushi (TSK) has been identified as playing an important role in modulating organ developmental processes, whole body energy expenditure and metabolic homeostasis (16)(17)(18)(19). Wang et al have identified TSK as a hepatokine that is tightly linked to the activation of thermogenesis and energy expenditure (20).…”

Section: Introductionmentioning

confidence: 99%

Elevated Serum Tsukushi Levels in Patients With Hyperthyroidism

et al. 2020

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Background: Tsukushi (TSK) is a secreted hepatokine recently identified as playing an important role in modulating glucose and lipid metabolism, and systemic energy homeostasis. However, information is not available regarding the association between circulating TSK and hyperthyroidism in humans. Methods: We measured serum TSK levels in 180 patients with hyperthyroidism and 82 healthy controls recruited from the clinic. Of them, 46 hyperthyroid patients received thionamide treatment for 3 months. Results: Hyperthyroid patients had higher levels of circulating TSK than healthy controls [186.67 (133.63-280.59) ng/ml vs. 97.27 (77.87-146.96) ng/ml, P < 0.001]. Subjects with higher level of serum free triiodothyronine (T3) and free thyroxine (T4) had higher levels of circulating TSK. In addition, serum TSK levels markedly declined with the improvement of thyroid function after thionamide treatment. In multivariable linear regression analyses, circulating TSK concentrations were significantly associated with serum free T3, free T4, thyroid stimulating hormone, thyrotropin receptor antibody, total cholesterol, low-density lipoprotein cholesterol (LDL-cholesterol), high-density lipoprotein cholesterol (HDL-cholesterol), and basal metabolic rate (all P < 0.01), adjusting for age, gender, smoking, and body mass index (BMI). Importantly, circulating TSK was significantly associated with risks of hyperthyroidism in multivariable logistic regression analyses, adjusting for age, gender, smoking, BMI, fasting glucose, LDL-cholesterol, and insulin resistance (HOMA-IR) [OR (95% CI), 1.012(1.005-1.019), P = 0.001]. Conclusion: These findings indicate that circulating TSK concentrations are independently associated with hyperthyroidism, suggesting that circulating TSK may be a predictive factor of hyperthyroidism and can be used for therapeutic monitoring.

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Tsukushi is essential for the development of the inner ear

Cited by 15 publications

References 43 publications

Protective Effects of N1-Methylnicotinamide Against High-Fat Diet- and Age-Induced Hearing Loss via Moderate Overexpression of Sirtuin 1 Protein

Protective Effects of N1-Methylnicotinamide Against High-Fat Diet- and Age-Induced Hearing Loss via Moderate Overexpression of Sirtuin 1 Protein

Embryologie, Fehlbildungen und seltene Erkrankungen der Cochlea

Elevated Serum Tsukushi Levels in Patients With Hyperthyroidism

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