A5085230647- Circadian rhythm and melatonin
- Neurobiology and Insect Physiology Research
- Adipose Tissue and Metabolism
- Insect and Arachnid Ecology and Behavior
- Estrogen and related hormone effects
- Retinoids in leukemia and cellular processes
- Muscle metabolism and nutrition
- Insect and Pesticide Research
- Psoriasis: Treatment and Pathogenesis
- Adipokines, Inflammation, and Metabolic Diseases
- Insect Resistance and Genetics
- Mitochondrial Function and Pathology
- Effects and risks of endocrine disrupting chemicals
- Birth, Development, and Health
- Autoimmune Bullous Skin Diseases
- Pancreatic function and diabetes
- Cancer Diagnosis and Treatment
- Metabolism, Diabetes, and Cancer
- Pregnancy and preeclampsia studies
- Exercise and Physiological Responses
- Healthcare and Venom Research
- Environmental Science and Water Management
- Antioxidant Activity and Oxidative Stress
- Chemical Synthesis and Analysis
- Nail Diseases and Treatments
Kyoto Prefectural University of Medicine
2017-2024
National Institutes of Health
2011-2023
National Institute of Environmental Health Sciences
2010-2019
Kyushu University
2004-2014
Fukuoka University
2007-2009
Deaconess Hospital
1993
Kanazawa Medical University
1987-1992
RORα and RORγ are expressed in human skin cells that produce the noncalcemic 20-hydroxyvitamin D3 [20(OH)D3] 20,23-dihydroxyvitamin [20,23(OH)2D3]. Chinese hamster ovary (CHO) stably expressing a Tet-on or expression vector ROR-responsive element (RORE)-LUC reporter, mammalian 2-hybrid model examining interaction between ligand binding domain (LBD) of with an LBD-interacting LXXLL-peptide, were used to study ROR-antagonist activities. These assays revealed 20(OH)D3 20,23(OH)2D3 function as...
Retinoic acid-related orphan receptors RORα and RORγ play a regulatory role in lipid/glucose homeostasis various immune functions, have been implicated metabolic syndrome several inflammatory diseases. RORα-deficient mice are protected against age- diet-induced obesity, hepatosteatosis, insulin resistance. The resistance to hepatosteatosis is related the reduced expression of genes regulating lipid synthesis, transport, storage. Adipose tissue-associated inflammation, which plays critical...
In this study, we demonstrate that the lack of retinoic acid-related orphan receptor (ROR) γ or α expression in mice significantly reduced peak level Cry1, Bmal1 , E4bp4 Rev-Erbα and Per2 an ROR isotype- tissue-selective manner without affecting phase their rhythmic expression. Analysis RORγ/RORα double knockout indicated certain tissues RORγ RORα exhibited a degree redundancy regulating clock gene Reporter analysis showed was able to induce reporter activity through RORE-containing...
The nuclear receptor TAK1/TR4/NR2C2 is expressed in several tissues that are important the control of energy homeostasis. In this study, we investigate whether TAK1 functions as a regulator lipid and homeostasis has role metabolic syndrome.We generated TAK1-deficient (TAK1⁻(/)⁻) mice to study function development syndrome aged fed high-fat diet (HFD). (Immuno)histochemical, biochemical, gene expression profile analyses were performed determine effect loss on liver adipose tissues. addition,...
Retinoid-related orphan receptor (ROR)α4 is the major RORα isoform expressed in adipose tissues and liver. In this study we demonstrate that RORα-deficient staggerer mice (RORα(sg/sg)) fed with a high-fat diet (HFD) exhibited reduced adiposity hepatic triglyceride levels compared wild-type (WT) littermates were resistant to development of steatosis, adipose-associated inflammation, insulin resistance. Gene expression profiling showed many genes involved synthesis storage, including Cidec,...
Background Psoriasis is a chronic inflammatory skin disorder involving marked immunological changes. IL-17-targeting biologics have been successful in reducing the disease burden of psoriasis patients with moderate-to-severe disease. Unfortunately, stratum corneum prevents penetration large molecule weight proteins, including monoclonal antibodies. Thus, for majority ineligible systemic treatments, small targeting RORγt, master regulator IL-17 family cytokines, may represent an alternative...
The hepatic circadian clock plays a key role in the daily regulation of glucose metabolism, but precise molecular mechanisms that coordinate these two biological processes are not fully understood. In this study, we identify novel connection between RORγ by machinery and diurnal metabolic networks. We demonstrate particularly at daytime, mice deficient exhibit improved insulin sensitivity tolerance due to reduced gluconeogenesis. This is associated with peak expression several genes critical...
Abstract Using LC/qTOF-MS we detected lumisterol, 20-hydroxylumisterol, 22-hydroxylumisterol, 24-hydroxylumisterol, 20,22-dihydroxylumisterol, pregnalumisterol, 17-hydroxypregnalumisterol and 17,20-dihydroxypregnalumisterol in human serum epidermis, the porcine adrenal gland. The hydroxylumisterols inhibited proliferation of skin cells a cell type-dependent fashion with predominant effects on epidermal keratinocytes. They also melanoma both monolayer soft agar. 20-Hydroxylumisterol...
Estrogen-related receptor γ (ERRγ), one of the 48 human nuclear receptors, has a fully active conformation with no ligand. We recently demonstrated that ERRγ binds strongly bisphenol A (BPA), nastiest endocrine disruptors, and thus retaining ERRγ's high basal constitutive activity. report BPA accumulates in maternal–fetal placental unit led us to hypothesize large amount might exist placenta. Here we evidence placenta indeed expresses exceptionally strongly. first ascertained presence nine...
Transcriptional regulation of insulin in pancreatic β-cells is mediated primarily through enhancer elements located within the 5' upstream regulatory region preproinsulin gene. Recently, Krüppel-like transcription factor, Gli-similar 3 (Glis3), was shown to bind (INS) promoter and positively influence transcription. In this report, we examined detail synergistic activation by Glis3 with coregulators, CREB-binding protein (CBP)/p300, duodenal homeobox 1 (Pdx1), neuronal differentiation...
Human brown fat is a potential therapeutic target for preventing obesity and related metabolic diseases by dissipating energy as heat through uncoupling protein 1 (UCP1). We have previously reported method to obtain chemical compound-induced adipocytes (ciBAs) converted from human dermal fibroblasts under serum-free conditions. However, pharmacological responses bioactive molecules been poorly characterised in ciBAs. This study showed that the treatment with Capsaicin, an agonist of...
The hepatic circadian clock plays a pivotal role in regulating major aspects of energy homeostasis and lipid metabolism. In this study, we show that RORγ robustly regulates the rhythmic expression several metabolic genes, including insulin-induced gene 2a, Insig2a, elongation very long chain fatty acids-like 3, Elovl3 sterol 12α-hydroxylase, Cyp8b1, by enhancing their at ZT20-4. time-dependent increase correlates with pattern RORγ. enhanced recruitment to ROREs promoter region, increased...
The transcription factor Glis-similar 3 (Glis3) has been implicated in the development of neonatal, type 1 and 2 diabetes. In this study, we examined spatiotemporal expression Glis3 protein during embryonic neonatal pancreas as well its function PP cells. To obtain greater insights into functions development, a knockin mouse strain expressing Glis3-EGFP fusion protein. Immunohistochemistry showed that was not detectable early pancreatic (E11.5 E12.5) at E13.5 15.5 expressed Ptf1a+ cells tip...
Brown fat is a therapeutic target for the treatment of obesity-associated metabolic diseases. However, nutritional intervention strategies increasing mass and activity human brown adipocytes have not yet been established. To identify vitamins required adipogenesis adipocyte browning, chemical compound-induced (ciBAs) were converted from dermal fibroblasts under serum-free vitamin-free conditions. Choline was found to be essential adipogenesis. Additional with pantothenic acid (PA) provided...
Retinoic acid-related orphan receptors (RORs) and the basic helix–loop–helix-PAS transcription factor Npas2 have been implicated in control of circadian rhythm. In this study, we demonstrate that RORγ directly regulates expression vivo. Although rhythmicity mRNA was maintained RORγ−/− mice, peak level significantly reduced several tissues, while loss RORα had little effect. Inversely, overexpression hepatoma Hepa1-6 cells greatly induced Npas2. RORγ-activated by binding two ROREs its...
Brown adipocytes play an important role in human energy metabolism and prevention of obesity diabetes. Induced pluripotent stem cells (iPSCs) represent a promising source for brown adipocytes; however, exogenous gene induction is generally required iPSCs generation, which might cause undesired effects particularly long-term treatment after transplantation. We have previously reported cocktail six small chemical compounds that enables conversion fibroblasts into compound-induced neuronal...
In this study, we identify Prospero-related homeobox 1 (Prox1) as a novel co-repressor of the retinoic acid-related orphan receptors, RORα and RORγ. Prox1 interacts directly with RORγ negatively regulates their transcriptional activity. The AF2 domain RORs is essential for interaction, whereas through either its 28 amino acids N-terminal region or C-terminal prospero-like domain. antagonists stabilize interaction between Prox1. homeodomain are critical repression ROR Chromatin...
Abstract Pigment‐dispersing factor (PDF), an 18‐amino acid neuropeptide, is a principal circadian neurotransmitter for the rhythms of locomotor activity in flies. Recently, two completely different types PDF precursor were clarified; that cricket Gryllus bimaculatus and last‐summer cicada Meimuna opalifera . The G. extraordinarily short comprises nuclear localization signal (NLS), while M ordinary length, comparable to seen precursors crustacean β‐PDH homologues. Although their peptide...