A5054090129- Adipose Tissue and Metabolism
- Growth Hormone and Insulin-like Growth Factors
- Metabolism and Genetic Disorders
- Childhood Cancer Survivors' Quality of Life
- Cardiovascular Function and Risk Factors
- Cancer, Hypoxia, and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Sexual Differentiation and Disorders
- Neonatal Health and Biochemistry
- Drug Transport and Resistance Mechanisms
- Genetics and Neurodevelopmental Disorders
- Pancreatic function and diabetes
- Cardiovascular Disease and Adiposity
- Renin-Angiotensin System Studies
- Diabetes Management and Research
- Mitochondrial Function and Pathology
- Peroxisome Proliferator-Activated Receptors
- Microtubule and mitosis dynamics
- Retinoids in leukemia and cellular processes
- Diabetes and associated disorders
- Diet and metabolism studies
- Pharmaceutical studies and practices
- Genetic Syndromes and Imprinting
- Neurogenetic and Muscular Disorders Research
- Birth, Development, and Health
Osaka City General Hospital
2022-2025
Kyoto Prefectural University of Medicine
2014-2024
Japanese Society for Dialysis Therapy
2023
University Hospital Kyoto Prefectural University of Medicine
2023
Universitätskinderklinik
2022
Universitätsklinikum Erlangen
2022
Koshigaya Municipal Hospital
2020
University of Alberta
2012-2019
Matsushita Memorial Hospital
2016
Duke University
2014
Obesity is increasing in prevalence and strongly associated with metabolic cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into 1-7. We studied the role of ACE2 obesity-mediated cardiac dysfunction. null (ACE2KO) wild-type (WT) mice were fed high-fat diet (HFD) or control at 6 months age. Loss resulted decreased weight gain...
Background— The angiotensin-converting enzyme 2 and angiotensin-(1–7) (Ang 1–7)/MasR (Mas receptor) axis are emerging as a key pathway that can modulate the development of diabetic cardiomyopathy. We studied effects Ang 1–7 on cardiomyopathy in db/db mice to elucidate therapeutic mechanism action. Methods Results— was administered 5-month-old male for 28 days via implanted micro-osmotic pumps. treatment ameliorated myocardial hypertrophy fibrosis with normalization diastolic dysfunction...
The renin-angiotensin system (RAS) may alter cardiac energy metabolism in heart failure. Angiotensin II (ANG II), the main effector of RAS failure, has emerged as an important regulator hypertrophy and metabolism. We studied metabolic perturbations insulin response ANG II-induced model. Ex vivo perfusion showed that hearts from II-treated mice had a lower to with significantly reduced rates glucose oxidation association increased pyruvate dehydrogenase kinase 4 (PDK4) levels. Palmitate were...
Background— Activation of the renin-angiotensin and sympathetic nervous systems may alter cardiac energy substrate preference, thereby contributing to progression heart failure with normal ejection fraction. We assessed qualitative quantitative effects angiotensin II (Ang II) α-adrenergic agonist, phenylephrine (PE), on metabolism in experimental models hypertrophy diastolic dysfunction role Ang type 1 receptor. Methods Results— (1.5 mg·kg −1 ·day ) or PE (40 was administered 9-week-old male...
Development of heart failure is known to be associated with changes in energy substrate metabolism. Information on the metabolism that occur limited and results vary depending methods employed. Our aim characterize pressure overload ischaemia–reperfusion (I/R) injury. We used transverse aortic constriction (TAC) mice induce overload-induced failure. Metabolic rates were measured isolated working hearts perfused at physiological afterload (80 mmHg) using 3H- or 14C-labelled substrates. As a...
The renin-angiotensin system, especially angiotensin II (ANG II), plays a key role in the development and progression of diabetic nephropathy. ANG 1–7 has counteracting effects on is known to exert beneficial We studied mechanism 1–7-induced nephropathy db/db mice. administered (0.5 mg·kg −1 ·day ) or saline 5-mo-old mice for 28 days via implanted micro-osmotic pumps. treatment reduced kidney weight ameliorated mesangial expansion increased urinary albumin excretion, characteristic features...
Abstract Context Somapacitan, a once-weekly reversible albumin-binding GH derivative, is evaluated in children with deficiency (GHD). Objective To demonstrate efficacy and safety of somapacitan vs daily GH. Methods REAL4 randomised, multinational, open-labeled, active-controlled parallel group phase 3 trial, comprising 52-week main trial 3-year extension (NCT03811535). Setting Eighty-six sites across 20 countries. Patients 200 treatment-naïve patients were randomized exposed. Interventions...
The lack of a severity definition and standardized GH cutoff level for deficiency (GHD) diagnosis in children leads to ambiguity the interpretation stimulation tests treatment recommendations. To investigate response differences among with GHD treated daily (somatropin) (year 1) or once-weekly somapacitan (years 1 2) based on peak concentrations assessed at diagnosis. This was subgroup analysis 200 patients aged ≥2.5 years participating REAL4 randomized, phase 3 trial. Height velocity (HV;...
Thyroid hormones, T3 and T4, are known regulators of intestine development. The best characterized example is the remodeling gastrointestinal tract during amphibian metamorphosis. hormones act via nuclear receptors, TRs, which T3-dependent transcription factors. We previously showed that intestinal epithelial cell proliferation controlled by thyroid TRα gene. To analyze mechanisms responsible, we studied expression genes belonging to and/or activated Wnt/β-catenin pathway, a major actor in...
Successful stem cell therapy requires the optimal proliferation, engraftment, and differentiation of cells into desired lineage tissues. However, clinical trials to date have had limited success, suggesting that a better understanding biology is needed. This includes energy metabolism because importance in proliferation differentiation. We report here first direct evidence human bone marrow mesenchymal (BMMSC) highly glycolytic with low rates mitochondrial oxidative metabolism. The...
The angiotensin II (ANG II)-ANG type 1 receptor (AT1R) axis is a key player in the pathophysiology of obesity. Angiotensin-converting enzyme 2 (ACE2) counteracts ANG II/AT1R via converting to 1-7 (Ang 1-7), which known have an anti-obesity effect. In this study, we hypothesized that ACE2 exerts strong effect by increasing Ang levels. We injected intraperitoneally recombinant human (rhACE2, 2.0 mg·kg-1·day-1) for 28 days high-fat diet (HFD)-induced obesity mice. rhACE2 treatment decreased...
The renin-angiotensin system is a key regulator of metabolism with beneficial effects the angiotensin 1-7 (Ang 1-7) peptide. We hypothesized that antiobesity effect Ang was related to stimulation brown adipose tissue (BAT). administered (0.54 mg kg-1 day-1) for 28 days via implanted micro-osmotic pumps mice high-fat diet (HFD)-induced obesity. treatment reduced body weight, upregulated thermogenesis, and ameliorated impaired glucose homeostasis without affecting food consumption....
Alterations in cardiac energy metabolism after a myocardial infarction contribute to the severity of heart failure (HF). Although fatty acid oxidation can be impaired HF, it is unclear if stimulating desirable approach treat HF. Both immediate and chronic malonyl coenzyme A decarboxylase inhibition, which decreases oxidation, improved function through enhancing efficiency post-myocardial rat that underwent permanent left anterior descending coronary artery ligation. The beneficial effects...
Abstract Context Daily growth hormone (GH) injections can be burdensome for patients and carers. Somapacitan is a long-acting, reversible albumin-binding GH derivative in development once-weekly administration with deficiency (GHD). Objective The objective of this study to evaluate the efficacy, safety, tolerability somapacitan vs once-daily GH. Design REAL 3 multicenter, randomized, controlled, double-blind (somapacitan doses), phase 2 26-week main extension (NCT02616562). Setting This took...
Somapacitan is a long-acting GH derivative for treatment of deficiency (GHD).Evaluate the efficacy and tolerability somapacitan in children with GHD after 2 years switch from daily GH.A randomized, multinational, open-labelled, controlled parallel group phase 3 trial, comprising 52-week main 3-year safety extension (NCT03811535).Eighty-five sites across 20 countries.A total 200 treatment-naïve prepubertal patients were randomized exposed; 194 completed 2-year period.Patients 2:1 to (0.16...
Abstract Objective Somapacitan is a long‐acting growth hormone (GH) derivative developed for the treatment of GH deficiency (GHD). This study evaluates efficacy and tolerability somapacitan in Japanese children with GHD after 104 weeks switch from daily GH. Design Subanalysis on patients randomised, open‐labelled, controlled parallel‐group phase 3 trial (REAL4, NCT03811535). Patients Measurements Thirty treatment‐naïve were randomised 2:1 to (0.16 mg/kg/week) or (0.034 mg/kg/day) up Week 52,...
Children with developmental disorders such as autism spectrum disorder (ASD) may not only develop type 2 diabetes mellitus (T2DM) due to psychosocial stress and overeating but also experience severe complications acute pancreatitis (AP) hypertriglyceridemia (HTG). Consequently, in pediatric patients concurrent T2DM disorders, a comprehensive approach is necessary that includes imaging evaluations for AP assessments of risk factors psychological metabolic abnormalities. We report the case...
Limited real-world data are available on persistence to growth hormone replacement therapy (GHRT) in Japan. Therefore, we used the Japan Medical Data Center claims database retrospectively investigate with GHRT patients pediatric deficiency (pGHD). We identified 1,020 pGHD treated GHRT. The mean age at initial diagnosis was 7.5 ± 3.8 years, and found a bimodal pattern age, peaks 3 12 13 years of age; were more pronounced male patients. After excluding early withdrawal, 1,016 eligible for...
Erythropoietin (EPO), clinically used as a hematopoietic drug, has received much attention due to its nonhematopoietic effects. EPO reportedly beneficial effects on obesity and diabetes mellitus. We investigated whether interscapular brown adipose tissue (iBAT: main part of classical BAT) could play role in EPO's anti-obesity anti-diabetic diet-induced obese mice. Four-week-old male C57BL/6J mice were fed high-fat diet (HFD-Con), half additionally given an intraperitoneal injection...
Differentiation-inducing factors (DIFs) are putative morphogens that induce cell differentiation in Dictyostelium discoideum. We previously reported DIF-3 activates glycogen synthase kinase-3beta (GSK-3beta), resulting the degradation of cyclin D1 HeLa cells. In this study, we investigated effect on mutants (R29Q, L32A, T286A, T288A, and T286A/T288A) to clarify precise mechanisms by which degrades revealed T286A/T288A were resistant DIF-3-induced compared with wild-type D1, indicating...
The COVID-19 pandemic, caused by the novel coronavirus, SARS-CoV-2, is threating our health systems and daily lives responsible for causing substantial morbidity mortality. In particular, aged individuals with comorbidities, including obesity, diabetes mellitus, hypertension, have significantly higher risks of hospitalization death than normal individuals. renin-angiotensin system (RAS) plays a pivotal role in pathogenesis hypertension. Angiotensin-converting enzyme 2 (ACE2), belonging to...
Background and aims Group 2 innate lymphoid cells (ILC2s) have been implicated in the regulation of metabolic homeostasis mice. Methods In this study, role ILC2s white adipose tissue (WAT) was investigated using ST2, an IL-33 receptor that is expressed on ILC2 knockout Results The deficiency ST2 decreased WAT, whereas ex-ILC2, which acquired group 1 cell (ILC1)-like traits, increased. This led to significant disorders such as visceral fat obesity, browning reduction energy metabolism,...
Partially hydrolyzed guar gum (PHGG) is a soluble dietary fiber derived through controlled enzymatic hydrolysis of gum, highly viscous galactomannan from the seeds Cyamopsis tetragonoloba. Here, we examined therapeutic potential supplementation with PHGG against sarcopenic obesity using Db/Db mice. mice fed normal diet alone or fiber-free diet, supplemented containing (5%), were examined. increased grip strength and weight skeletal muscles. short-chain fatty acids (SCFAs) concentration in...