Updated on 2023/10/10


Research Institute of Environmental Medicine Designated professor
Designated professor

Degree 1

  1. 博士(医学) ( 1999.3   京都大学 ) 


Papers 11

  1. 多職種連携 必携キー・ノート 多職種連携による肥満治療の効果的な動機付けQ&A

    浅原 哲子, 加藤 さやか, 岩佐 真代, 池上 健太郎, 若林 大

    糖尿病・内分泌プラクティスWeb     page: 外来では肥満患者にどのように動機付けをするとよいでしょうか?良いツールはありますか?   2023.7

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    DOI: 10.57554/a0058

    CiNii Research

  2. Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis Reviewed

    Iwasa M., Kato H., Iwashita K., Yamakage H., Kato S., Saito S., Ihara M., Nishimura H., Kawamoto A., Suganami T., Tanaka M., Satoh-Asahara N.

    Nutrients   Vol. 15 ( 12 )   2023.6

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Nutrients  

    Type 2 diabetes mellitus is associated with an increased risk of dementia, potentially through multifactorial pathologies, including neuroinflammation. Therefore, there is a need to identify novel agents that can suppress neuroinflammation and prevent cognitive impairment in diabetes. In the present study, we demonstrated that a high-glucose (HG) environment elevates the intracellular reactive oxygen species (ROS) levels and triggers inflammatory responses in the mouse microglial cell line BV-2. We further found that thioredoxin-interacting protein (TXNIP), a ROS-responsive positive regulator of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, was also upregulated, followed by NLRP3 inflammasome activation and subsequent interleukin-1beta (IL-1β) production in these cells. Conversely, caspase-1 was not significantly activated, suggesting the involvement of noncanonical pathways in these inflammatory responses. Moreover, our results demonstrated that taxifolin, a natural flavonoid with antioxidant and radical scavenging activities, suppressed IL-1β production by reducing the intracellular ROS levels and inhibiting the activation of the TXNIP–NLRP3 axis. These findings suggest the novel anti-inflammatory effects of taxifolin on microglia in an HG environment, which could help develop novel strategies for suppressing neuroinflammation in diabetes.

    DOI: 10.3390/nu15122738


  3. Cystatin C-based eGFR predicts cardiovascular disease in patients with overweight/obesity and hyperglycemia

    Suzuki K., Tsujiguchi H., Hara A., Nakamura H., Kotani K., Noda M., Yamakage H., Satoh-Asahara N., Takamura T.

    Obesity Science and Practice   Vol. 9 ( 1 ) page: 4 - 14   2023.2

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    Publisher:Obesity Science and Practice  

    Background: Although many clinical parameters have been identified as predictors for cardiovascular disease (CVD) development in the general population, the accurate predictor for CVD in patients with obesity is still unknown. Objective: The study aimed to explore an additional risk factor and predictor for CVD in patients with overweight/obesity considering the interaction of obesity-related pathophysiology. Methods: The Japan Obesity and Metabolic Syndrome study, a multicenter prospective study, enrolled 787 outpatients, of which 318 eligible patients were analyzed. Patients with fasting plasma glucose (FPG) levels ≥6.11 and < 6.11 mmol/L were considered to have high FPG (HFPG) and normal FPG (NFPG), respectively. Thirty-six patients who developed CVD during the 5 years follow-up were assigned to the CVD group. Results: Cox's proportional hazards model revealed no significant association between CVD and cystatin C-based estimated glomerular filtration rate (eGFRcys) or creatinine-based eGFR (eGFRcr) in the NFPG group. In the HFPG group, lower eGFRcys, but not eGFRcr, was significantly associated with CVD development. A generalized linear mixed model demonstrated greater reduction in eGFRcys levels over time with HFPG than with NFPG. Although the CVD group showed gradual reduction in eGFRcys levels, the non-CVD group—matched using propensity scores—did not show a decline in eGFRcys levels. Conclusions: Lower eGFRcys levels may be more accurate than eGFRcr in predicting CVD development in patients with overweight/obesity and hyperglycemia. Furthermore, eGFRcys reduction over time is associated with CVD development. Clinical Trial Registry Number: UMIN000000559.

    DOI: 10.1002/osp4.630


  4. Novel Therapeutic Potentials of Taxifolin for Obesity-Induced Hepatic Steatosis, Fibrogenesis, and Tumorigenesis

    Inoue T., Fu B., Nishio M., Tanaka M., Kato H., Tanaka M., Itoh M., Yamakage H., Ochi K., Ito A., Shiraki Y., Saito S., Ihara M., Nishimura H., Kawamoto A., Inoue S., Saeki K., Enomoto A., Suganami T., Satoh-Asahara N.

    Nutrients   Vol. 15 ( 2 )   2023.1

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    The molecular pathogenesis of nonalcoholic steatohepatitis (NASH) includes a complex interaction of metabolic stress and inflammatory stimuli. Considering the therapeutic goals of NASH, it is important to determine whether the treatment can prevent the progression from NASH to hepatocellular carcinoma. Taxifolin, also known as dihydroquercetin, is a natural bioactive flavonoid with antioxidant and anti-inflammatory properties commonly found in various foods and health supplement products. In this study, we demonstrated that Taxifolin treatment markedly prevented the development of hepatic steatosis, chronic inflammation, and liver fibrosis in a murine model of NASH. Its mechanisms include a direct action on hepatocytes to inhibit lipid accumulation. Taxifolin also increased brown adipose tissue activity and suppressed body weight gain through at least two distinct pathways: direct action on brown adipocytes and indirect action via fibroblast growth factor 21 production in the liver. Notably, the Taxifolin treatment after NASH development could effectively prevent the development of liver tumors. Collectively, this study provides evidence that Taxifolin shows pleiotropic effects for the treatment of the NASH continuum. Our data also provide insight into the novel mechanisms of action of Taxifolin, which has been widely used as a health supplement with high safety.

    DOI: 10.3390/nu15020350


  5. Analysis of time-dependent changes in the FIB4 index in patients with obesity receiving weight reduction therapy

    Kawai S., Yamakage H., Kotani K., Noda M., Satoh-Asahara N., Hashimoto K.

    Scientific Reports   Vol. 12 ( 1 )   2022.12

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    Publisher:Scientific Reports  

    Weight reduction therapy represents a fundamental strategy to prevent nonalcoholic fatty liver disease (NAFLD) in patients with obesity, which may result in liver fibrosis. Histological findings previously demonstrated that weight reduction therapy attenuated NAFLD. The FIB4 index is widely used to assess the status of NAFLD. The present study investigated whether the FIB4 index improved during weight reduction therapy. We used cohort data of the Japan Obesity and Metabolic syndrome Study and examined the correlation between body weight (BW) loss (BW loss) and changes in the FIB4 index (ΔFIB4 index) in patients who successfully reduced their BW by more than 5% from baseline BW after 3, 6, and 12 months (M) of weight reduction therapy. A negative correlation (r = −0.342, p = 0.029) was observed between BW loss and FIB4 index after 3 M, but not after 6 M, whereas a positive correlation (r = 0.298, p = 0.03) was noted after 12 M. These results revealed changes in the correlation between ΔBW loss and ΔFIB4 index during the therapy, mainly due to time-dependent changes in components of the FIB4 index formula. Thus, we concluded that the FIB4 index is useful and reliable to assess liver fibrosis until 3 M during weight reduction therapy. However, after 3 M, we should recognize that the FIB4 index may not reflect liver status. Therefore, it is important to consider this characteristic of the FIB4 index as a limitation when assessing liver fibrosis in obese patients receiving weight reduction therapy.

    DOI: 10.1038/s41598-022-19420-0


  6. Soluble TREM2 and Alzheimer-related biomarker trajectories in the blood of patients with diabetes based on their cognitive status

    Satoh-Asahara N., Yamakage H., Tanaka M., Kawasaki T., Matsuura S., Tatebe H., Akiguchi I., Tokuda T.

    Diabetes Research and Clinical Practice   Vol. 193   2022.11

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    Publisher:Diabetes Research and Clinical Practice  

    Aim: We aimed to elucidate the dynamics of blood biomarkers according to the severity of cognitive impairment in patients with type 2 diabetes mellitus (DM) and to identify useful biomarkers for diabetes-related dementia. Methods: This was a cross-sectional, nested case-control study of 121 Japanese DM and non-DM patients with different levels of cognitive functioning. We evaluated participants’ cognitive functions, blood biomarkers related to Alzheimer's disease, and soluble triggering receptors expressed on myeloid cells 2 (sTREM2). We then compared these biomarkers between the DM and non-DM and across the different cognitive strata. Results: In all cognitive strata, significantly lower levels of serum sTREM2 were observed in the DM than in the non-DM. We also found that plasma levels of phosphorylated tau (p-tau) increased with increasing levels of cognitive decline in both the DM and non-DM. However, this was accompanied by a decrease in plasma amyloid-β(Aβ42/Aβ40 ratios in non-DM only. Conclusion: This study revealed novel characteristic trajectories of dementia-related blood biomarkers in diabetes-related dementia, suggesting the pathological involvement of molecular cascades initiated by impaired microglial activation. This results in decreased serum sTREM2, followed by tauopathy without substantial amyloid plaques, reflected by plasma p-tau elevation with no decrease in the Aβ42/Aβ40 ratio. Clinical trials (the unique trial number and the name of the registry): UMIN000048032, https://www.umin.ac.jp.

    DOI: 10.1016/j.diabres.2022.110121


  7. Ameliorating prediabetic subject status via fermented tea supplementation: A randomized, double-blind, parallel-group comparison study

    Katanasaka Y., Sunagawa Y., Miyazaki Y., Funamoto M., Shimizu S., Shimizu K., Yamakage H., Satoh-Asahara N., Toyama K., Sabashi T., Suzuki M., Hamabe-Horiike T., Komiyama M., Wada H., Mori K., Hasegawa K., Morimoto T.

    Journal of Functional Foods   Vol. 97   2022.10

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    Publisher:Journal of Functional Foods  

    Fermented tea consumption has been reported to alleviate diabetes and dyslipidemia, inducing an antiobesity effect. Here, we investigated the effects of microbial fermented tea and microbial fermented twig tea, which are made from Camellia sinensis by fermentation with Aspergillus sp., on glucose tolerance and metabolic syndrome in prediabetic subjects in a randomized, double-blind study. They were asked to consume the tea three times a day for 12 weeks. Fasting blood glucose, HbA1c, and 2-h oral glucose tolerance test (OGTT) were measured as primary endpoints. After 12 weeks, fasting blood glucose level was significantly reduced in the microbial fermented twig tea group (n = 19) as compared with that in the microbial fermented tea group (n = 16, p = 0.017). There was no significant difference in the 2-hour OGTT and HbA1c values between the two groups. Triglyceride levels were significantly lower in the microbial fermented tea group than in the microbial fermented twig tea group at 12 weeks (p = 0.049).

    DOI: 10.1016/j.jff.2022.105257


  8. Higher Serum Soluble TREM2 as a Potential Indicative Biomarker for Cognitive Impairment in Inadequately Controlled Type 2 Diabetes Without Obesity: The DOR-KyotoJ-1

    Tanaka M., Yamakage H., Muranaka K., Yamada T., Araki R., Ogo A., Matoba Y., Watanabe T., Saito M., Kurita S., Yonezawa K., Tanaka T., Suzuki M., Sawamura M., Matsumoto M., Nishimura M., Kusakabe T., Wada H., Hasegawa K., Kotani K., Noda M., Satoh-Asahara N.

    Frontiers in Endocrinology   Vol. 13   2022.5

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    Publisher:Frontiers in Endocrinology  

    Objective: Type 2 diabetes is a risk factor for dementia. We investigated whether serum levels of soluble triggering receptor expressed on myeloid cell 2 (sTREM2), a soluble form of the cell surface receptor TREM2, were predictive of cognitive impairment in type 2 diabetes without obesity. Methods: A total of 166 Japanese patients with type 2 diabetes without obesity were followed-up for 2 years. We measured clinical parameters, assessed cognitive function using the mini-mental state examination (MMSE), quantified and divided serum sTREM2 levels into quartiles, and examined the longitudinal associations. Results: During the follow-up, HbA1c levels were elevated in 98 patients and decreased in 68 patients. In the HbA1c-elevated group, higher sTREM2 levels at baseline showed a significant association with a greater tendency for reduction in MMSE scores (P for trend = 0.015), whereas they were not significantly associated with other examined parameters. In the HbA1c-decreased group, there was no significant association between sTREM2 levels at baseline and changes in MMSE scores, but higher sTREM2 levels at baseline were significantly associated with a greater tendency for reduction in waist circumference (P for trend = 0.027), homeostasis model assessment of insulin resistance (P for trend = 0.039), and sTREM2 levels (P for trend = 0.023). Conclusions: Glycemic control is suggested to be important in preventing cognitive impairment in patients with type 2 diabetes without obesity. Higher serum sTREM2 levels would be a predictive marker for cognitive impairment in inadequately controlled type 2 diabetes without obesity.

    DOI: 10.3389/fendo.2022.880148


  9. A Large Cohort-Based Study on the Development of an Early Evaluation System and Treatment Strategies for Brain-Cardio-Renal Complications in Patients With Diabetes and Obesity

    Asahara Noriko

    Journal of the Japan Diabetes Society   Vol. 65 ( 3 ) page: 75 - 80   2022.3

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    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:THE JAPAN DIABETES SOCIETY  

    DOI: 10.11213/tonyobyo.65.75

    CiNii Research

  10. Prevention of Worsening Diabetes through Behavioral Changes by an IoT-based Self-Monitoring System in Japan (PRISM-J): Study design and rationale for a multicenter, open-label, randomized parallel-group trial

    Bouchi Ryotaro, Izumi Kazuo, Ohtsu Hiroshi, Miyo Kengo, Tanaka Shigeho, Satoh-Asahara Noriko, Hara Kazuo, Odawara Masato, Kusunoki Yoshiki, Koyama Hidenori, Onoue Takeshi, Arima Hiroshi, Tsushita Kazuyo, Watada Hirotaka, Kadowaki Takashi, Ueki Kohjiro

    GHM Open   Vol. 1 ( 1 ) page: 3 - 11   2021.8

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    Language:English   Publisher:National Center for Global Health and Medicine  

    <p>The use of the Internet-of-Things has improved glycemic control in individuals with diabetes in several small-scale studies with a short follow-up period. This large-scale randomized controlled trial investigates whether a smartphone-based self-management support system prevents the worsening of glycemic control in individuals with type 2 diabetes. Individuals with type 2 diabetes (age range 20-74 years; <i>n</i> = 2,000) will be recruited, enrolled, and randomly assigned to two groups: the intensive therapy group and the conventional therapy group. Participants in the intensive therapy group will be supervised to use an automated Internet-of-Things system that demonstrates a summary of lifelogging data (<i>e.g.</i>, weight, blood pressure, and daily activities) obtained from each measurement device and will receive feedback messages <i>via</i> smartphone applications to encourage them to increase their physical activity and to monitor weight and blood pressure. Participants in the conventional therapy group are allowed to use the same measurement devices as part of the routine diabetes care but without the Internet-of-Things system. The primary endpoint is the between-group difference in HbA1c levels from baseline to 52 weeks. This randomized controlled study will test the hypothesis that an Internet-of-Things-based self-monitoring system could effectively prevent the worsening of diabetes in individuals with type 2 diabetes. The expected results of the study should facilitate the development of novel strategies for both diabetes treatment and social health.</p>

    DOI: 10.35772/ghmo.2021.01004

    CiNii Research

  11. The Multi-Domain Intervention Trial in Older Adults With Diabetes Mellitus for Prevention of Dementia in Japan: Study Protocol for a Multi-Center, Randomized, 18-Month Controlled Trial

    Sugimoto T., Araki A., Fujita H., Honda K., Inagaki N., Ishida T., Kato J., Kishi M., Kobayashi K., Kouyama K., Noma H., Ohishi M., Satoh-Asahara N., Shimada H., Sugimoto K., Suzuki S., Takeya Y., Tamura Y., Tokuda H., Umegaki H., Watada H., Yamada Y., Sakurai T.

    Frontiers in Aging Neuroscience   Vol. 13   2021.7

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    Publisher:Frontiers in Aging Neuroscience  

    Background: The Japan-Multi-domain Intervention Trial for Prevention of Dementia in Older Adults with Diabetes (J-MIND-Diabetes) is an 18-month, multi-centered, open-labeled, randomized controlled trial designed to identify whether multi-domain intervention targeting modifiable risk factors for dementia could prevent the progression of cognitive decline among older adults with type 2 diabetes mellitus (T2DM). This manuscript describes the study protocol for the J-MIND-Diabetes trial. Materials and Methods: Subjects of this trial will comprise a total of 300 T2DM outpatients aged 70–85 years with mild cognitive impairment. Subjects will be centrally randomized into intervention and control groups at a 1:1 allocation ratio using the stratified permuted-block randomization methods. The intervention group will participate in multi-domain intervention programs aimed at: (1) management of metabolic and vascular risk factors; (2) physical exercise and self-monitoring of physical activity; (3) nutritional guidance; and (4) social participation. The control group will receive usual T2DM care and general instructions on dementia prevention. The primary and secondary outcomes will be assessed at baseline, at 6- and 18-month follow-up. The primary outcome is change from baseline at 18 months in a global composite score combining several neuropsychological domains, including global cognitive function, memory, attention, executive function, processing speed and language. Secondary outcomes include: (1) cognitive changes in neuropsychological tests; (2) changes in geriatrics assessments; (3) metabolic control and diabetic complications; (4) changes in blood and urinary markers. Discussion: This trial will be the first trial to demonstrate the effectiveness of multi-domain intervention in preventing cognitive decline in older adults with T2DM at increased risk of dementia in Japan. Trial Registration: UMIN000035911; Registered on the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) 18 February 2019. (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000040908).

    DOI: 10.3389/fnagi.2021.680341


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  1. Obesity

    Noriko Satoh-Asahara

      Vol. 278 ( 5 ) page: 376 - 381   2021.7

  2. TREM2


    老年内科   Vol. 3 ( 6 ) page: 739 - 748   2021.6

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    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)