A5010911259- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Regulation of Appetite and Obesity
- Peroxisome Proliferator-Activated Receptors
- Pancreatic function and diabetes
- Sirtuins and Resveratrol in Medicine
- Metabolism, Diabetes, and Cancer
- Vitamin C and Antioxidants Research
- Signaling Pathways in Disease
- Cardiovascular Disease and Adiposity
- Diabetes Management and Research
- Genetic Associations and Epidemiology
- Diabetes and associated disorders
- Genomics and Chromatin Dynamics
- Pharmacology and Obesity Treatment
- Pluripotent Stem Cells Research
- Immune cells in cancer
- Genetics, Aging, and Longevity in Model Organisms
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Cytokine Signaling Pathways and Interactions
- Hair Growth and Disorders
- Nutrition, Genetics, and Disease
- Protein Kinase Regulation and GTPase Signaling
- Natural Antidiabetic Agents Studies
- Soft tissue tumor case studies
The University of Tokyo
2013-2024
Kagawa University
2024
Diabetes Australia
2010-2012
National Institute of Infectious Diseases
2004
We previously demonstrated that insulin receptor substrate 2 (Irs2) KO mice develop diabetes associated with hepatic resistance, lack of compensatory beta cell hyperplasia, and leptin resistance. To more precisely determine the roles Irs2 in cells hypothalamus, we generated cell-specific hypothalamus-specific knockdown (betaHT-IRS2) mice. Expression mRNA was reduced by approximately 90% pancreatic islets markedly arcuate nucleus hypothalamus. By contrast, expression liver, muscle, adipose...
Identification of regulatory elements within the genome is crucial for understanding mechanisms that govern cell type–specific gene expression. We generated genome-wide maps open chromatin sites in 3T3-L1 adipocytes (on day 0 and 8 differentiation) NIH-3T3 fibroblasts using formaldehyde-assisted isolation coupled with high-throughput sequencing (FAIRE-seq). FAIRE peaks at promoter were associated active transcription histone modifications H3K4me3 H3K27ac. Non-promoter characterized by...
To identify a novel susceptibility locus for type 2 diabetes, we performed an imputation-based, genome-wide association study (GWAS) in Japanese population using newly obtained imputed-genotype data 229 890 single-nucleotide polymorphisms (SNPs) estimated from previously reported, directly genotyped GWAS the same samples (stage 1: 4470 diabetes versus 3071 controls). We 43 new SNPs with P-values of <10(-4) part stage-1 (2692 controls), and associations validated were evaluated another 11 139...
AMP-activated protein kinase (AMPK) is a serine/threonine that functions as sensor to maintain energy balance at both the cellular and whole-body levels therefore potential target for drug design against metabolic syndrome, obesity type 2 diabetes. Here, crystal structure of phosphorylated-state mimic T172D mutant domain from human AMPK α2 subunit reported in apo form complex with selective inhibitor, compound C. The exhibits typical bilobal fold exists monomer crystal. Like wild-type form,...
Abstract Obesity is among the risk factors for male infertility. Although several mechanisms underlying obesity-induced subfertility have been reported, entire mechanism of infertility still remains unclear. Here, we show that sperm count, motility and fertilizing ability were decreased in mice fed a high-fat diet expression AdipoR1 gene protein was decreased, pro-apoptotic genes increased, testis from diet. Moreover, demonstrate testes weight, significantly knockout compared to those...
Genetically modified mouse models are essential for in vivo investigation of gene function and human disease research. Targeted mutations can be introduced into embryos using genome editing technology such as CRISPR-Cas. Although mice with small indel produced, the production carrying large deletions or fragment knock-in alleles remains inefficient. We nuclear localisation property Cdt1 protein CRISPR-Cas system efficient genetically engineered mice. Mouse Cdt1-connected Cas9 (Cas9-mC) was...
Knowledge of the regulatory factors associated with down‐regulation adiponectin gene expression and up‐regulation PAI‐1 is crucial to understand pathophysiological basis obesity metabolic diseases, could establish new treatment strategies for these conditions. We showed that 5‐HT 2A receptors was up‐regulated in hypertrophic 3T3‐L1 adipocytes, which exhibited decreased increased PAI‐1. receptor antagonists suppression enhanced expression. Activation Gq negatively regulated expression,...
Abstract Adiponectin receptors, AdipoR1 and AdipoR2 exert anti-diabetic effects. Although muscle-specific disruption of has been shown to result in decreased insulin sensitivity exercise endurance, it remains be determined whether upregulation could reverse them obese diabetic mice. Here, we show that expression human increased levels genes involved mitochondrial biogenesis oxidative stress-detoxification almost the same extents as treadmill exercise, concomitantly endurance Moreover,...
Apolipoprotein E (apoE) and its receptor, very low density lipoprotein receptor (VLDLR), are involved in fat accumulation adipocytes. Here, we investigated the effect of a peroxisome proliferator-activated (PPAR) gamma agonist, rosiglitazone, on regulation VLDLR expression both white adipose tissue (WAT) obese mice cultured Furthermore, to determine whether rosiglitazone directly regulates transcription gene, carried out luciferase assay with reporter gene containing mouse promoter region,...
Abstract The human adiponectin receptors, AdipoR1 and AdipoR2, are key anti-diabetic molecules. We previously reported the crystal structures of revealing that their seven transmembrane helices form an internal closed cavity (the form). In this study, we determined structure D208A variant AdipoR1, which is fully active with respect to major downstream signaling. Among three molecules in asymmetric unit, two assume form, other adopts open large openings cavity. Between closed- open-form...
Adiponectin receptors, AdipoR1 and AdipoR2 are promising targets for the prevention treatment of metabolic diseases. In this study, we aimed to establish agonistic antibodies against with a long enough half-life provide means improving poor medication adherence associated preclinical small-molecule AdipoR agonists or existing antidiabetic drugs. Monoclonal were obtained by immunizing knockout mice human AdipoR-expressing cells. Of shown bind both, an agonist antibody was obtained, which...