A5035669988- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- Muscle Physiology and Disorders
- Protein Kinase Regulation and GTPase Signaling
- Kruppel-like factors research
- Peroxisome Proliferator-Activated Receptors
- Endoplasmic Reticulum Stress and Disease
- Diet, Metabolism, and Disease
- Liver physiology and pathology
- Autophagy in Disease and Therapy
- PI3K/AKT/mTOR signaling in cancer
- Lipid metabolism and biosynthesis
- Cancer, Hypoxia, and Metabolism
- Diabetes Treatment and Management
- Genetic Syndromes and Imprinting
- Angiogenesis and VEGF in Cancer
- Exercise and Physiological Responses
- FOXO transcription factor regulation
- Cancer-related gene regulation
- Retinoids in leukemia and cellular processes
- Antioxidant Activity and Oxidative Stress
- Neurogenetic and Muscular Disorders Research
Kobe University
2013-2024
University of Shizuoka
2021-2024
Food & Nutrition
2024
National Institute of Biomedical Innovation, Health and Nutrition
2023
University of Oxford
2023
Beth Israel Deaconess Medical Center
2009-2015
Harvard University
2009
Red Cross Hospital
1998
Retinol-binding protein 4 (RBP4), the sole retinol transporter in blood, is secreted from adipocytes and liver. Serum RBP4 levels correlate highly with insulin resistance, other metabolic syndrome factors, cardiovascular disease. Elevated serum causes but molecular mechanisms are unknown. Here we show that induces expression of proinflammatory cytokines mouse human macrophages thereby indirectly inhibits signaling cocultured adipocytes. This occurs through activation c-Jun N-terminal kinase...
Diabetes mellitus is associated with various disorders of the locomotor system including decline in mass and function skeletal muscle. The mechanism underlying this association has remained ambiguous, however. We now show that abundance transcription factor KLF15 as well expression genes related to muscle atrophy are increased diabetic model mice, mice muscle-specific deficiency protected from diabetes-induced mass. Hyperglycemia was found upregulate protein animals, which achieved via...
The gut microbiome has emerged as a key regulator of obesity; however, its role in brown adipose tissue (BAT) metabolism and association with obesity remain to be elucidated. We found that the levels circulating branched-chain amino acids (BCAA) their cognate α-ketoacids (BCKA) were significantly correlated body weight humans mice BCAA catabolic defects BAT associated diet-induced (DIO) mice. Pharmacological systemic enhancement activity reduced plasma BCKA protected against these effects...
Although immobility is a common cause of muscle atrophy, the mechanism underlying this causality unclear. We here show that Krüppel-like factor 15 (KLF15) and IL-6 are upregulated in skeletal limb-immobilized mice with KLF15 deficiency or systemic protected from immobility-induced atrophy. A newly developed Ca2+ bioimaging revealed cytosolic concentration ([Ca2+]i) reduced to below basal level by immobilization, which associated downregulation Piezo1. Acute disruption Piezo1 induced Klf15...
Pancreatic beta cell failure is thought to underlie the progression from glucose intolerance overt diabetes, and ER stress implicated in such dysfunction. We have now shown that transcription factor CCAAT/enhancer-binding protein (C/EBPbeta) accumulated islets of diabetic animal models as a result before onset hyperglycemia. Transgenic overexpression C/EBPbeta specifically cells mice reduced mass lowered plasma insulin levels, resulting development diabetes. Conversely, genetic ablation...
The small G-protein ras-related C3 botulinum toxin substrate 1 (RAC1) plays various roles in mammalian cells, such as the regulation of cytoskeletal organisation, cell adhesion, migration and morphological changes. present study examines effects RAC1 ablation on pancreatic beta function. Isolated islets from cell-specific Rac1-knockout (betaRac1 −/−) mice knockdown INS-1 insulinoma cells treated with interfering RNA were used to investigate insulin secretion organisation cells. BetaRac1 −/−...
In the liver, signal transducer and activator of transcription 3 (STAT3) plays an important role in suppression gluconeogenic enzyme expression. While obesity-associated endoplasmic reticulum (ER) stress has been shown to increase hepatic expression, ER STAT3-dependent regulation such expression is unclear. The current study aimed elucidate effect on Genetically obese/diabetic db/db mice mouse–derived isolated hepatocytes were used as models. A tyrosine phosphatase inhibitor, a deacetylation...
Significance Recently, the potassium voltage-gated channel, KQT-like subfamily Q, member1 ( KCNQ1 ) gene has received much attention as a candidate susceptibility for type 2 diabetes in Asian, European, and other populations. The molecular mechanism underlying association of with onset remained unclear; however, we have now found that paternal allelic mutation Kcnq1 results up-regulation neighboring imprinted cyclin-dependent kinase inhibitor 1C Cdkn1c ), cell cycle inhibitor, pancreatic...
Abstract The antidiabetic drug pioglitazone ameliorates insulin resistance by activating the transcription factor PPARγ. In addition to its blood glucose–lowering action, exerts pleiotropic effects including amelioration of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). mechanism which achieves this latter effect has remained unclear, however. We here show that administration increases amount linoleic acid (LA) metabolites in adipose tissue KK-Ay mice. These...
The development of type 2 diabetes is accompanied by a progressive decline in β-cell mass and function. Vildagliptin, dipeptidyl peptidase 4 inhibitor, representative new class antidiabetic agents that act through increasing the expression glucagon-like peptide-1. protective effect this agent on β cells was studied diabetic mice. Diabetic pancreatic cell-specific C/EBPB transgenic (TG) mice exhibit decreased associated with increased apoptosis, proliferation, aggravated endoplasmic reticulum...
Elevated levels of serum retinol-binding protein 4 (RBP4) contribute to insulin resistance and correlate with increased prevalence hypertension myocardial infarction. We sought determine whether lowering RBP4 would improve blood pressure (BP) protect against obesity- or angiotensin (Ang)-II-induced hypertension. Systolic diastolic BP were lower in the RBP4-knockout (RBP4-KO) mice higher RBP4-overexpressing (RBP4-Tg) compared wild-type (WT) littermates. Carbachol-induced vasodilatation was...
Although adipocytes are major targets of insulin, the influence impaired insulin action in on metabolic homeostasis remains unclear. We here show that adipocyte-specific PDK1 (3'-phosphoinositide-dependent kinase 1)-deficient (A-PDK1KO) mice manifest actions adipose tissue and reduction mass. A-PDK1KO developed resistance, glucose intolerance, hepatic steatosis, this phenotype was suppressed by additional ablation FoxO1 specifically (A-PDK1/FoxO1KO mice) without an effect Neither circulating...
Insulin regulates various biological processes in adipocytes, and adipose tissue dysfunction due to insulin resistance this plays a central role the development of metabolic diseases, including NAFLD NASH. However, combined impact dietary factors on pathogenesis NAFLD-NASH has remained unknown.3'-phosphoinositide-dependent kinase 1 (PDK1) is serine-threonine protein that mediates actions insulin. We recently showed adipocyte-specific PDK1 knockout (A-PDK1KO) mice maintained normal chow...
Insulin promotes glucose uptake in skeletal muscle by inducing the translocation of transporter GLUT4 to plasma membrane. The serine/threonine kinase Akt2 has been implicated as a key regulator this insulin action. However, mechanisms whereby regulates multiple steps remain incompletely understood. Recently, small GTPase Rac1 identified muscle-specific insulin-stimulated uptake. Here, we show that is critical downstream component pathway mouse well cultured myocytes. induced constitutively...
5'-Adenosine monophosphate-activated protein kinase (AMPK) is a potential therapeutic target for various medical conditions. We here identify small-molecule compound (RX-375) that activates AMPK and inhibits fatty acid synthesis in cultured human hepatocytes. RX-375 does not bind to but interacts with prohibitins (PHB1 PHB2), which were found form complex AMPK. induced dissociation of this complex, PHBs knockdown resulted activation, the cells. Administration obese mice activated ameliorated...
Nicotinamide adenine dinucleotide (NAD+) -dependent protein deacetylase SIRT1 plays an important role in the regulation of metabolism. Although administration nicotinamide mononucleotide (NMN), a key NAD+ intermediate, has been shown to ameliorate metabolic disorders, such as insulin resistance and glucose intolerance, direct effect NMN on lipid metabolism adipocytes remains unclear. We here investigated storage 3T3-L1 differentiated adipocytes. Oil-red O staining showed that treatment...
The transcriptional coactivator PGC-1α has been implicated in the regulation of multiple metabolic processes. However, previously reported phenotypes mice deficient have inconsistent. exists as isoforms, including variants transcribed from an alternative first exon. We show here that are main entity increases during exercise. These variants, unlike canonical isoform PGC-1α, robustly upregulated human skeletal muscle after Furthermore, extent this upregulation correlates with oxygen...
Insulin-stimulated glucose uptake in skeletal muscle is mediated by the translocation of transporter GLUT4 from intracellular storage sites to plasma membrane. The small GTPase Rac1 has been implicated this insulin signalling, but mechanism whereby stimulates remains obscure. In present study, we examined role RalA downstream fibres isolated genetically modified mice. A dominant-negative mutant RalA, when ectopically overexpressed, significantly reduced response or either one constitutively...