A5018854168- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Biochemical Analysis and Sensing Techniques
- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Nuclear Structure and Function
- Hormonal Regulation and Hypertension
- Diabetes Treatment and Management
- Peroxisome Proliferator-Activated Receptors
- Nutrition, Genetics, and Disease
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- Diet and metabolism studies
- Cholesterol and Lipid Metabolism
- Neuroendocrine Tumor Research Advances
- Neurogenesis and neuroplasticity mechanisms
- Cancer, Lipids, and Metabolism
- Liver Disease Diagnosis and Treatment
- Lipid metabolism and disorders
- Diabetes and associated disorders
- RNA and protein synthesis mechanisms
- Diet, Metabolism, and Disease
- Receptor Mechanisms and Signaling
- melanin and skin pigmentation
Jichi Medical University
2016-2025
Kyoto University
2008-2022
Kyoto University Hospital
2011-2022
University of Toyama
2017-2019
Jichi Medical University Hospital
2018
Kanazawa University
2012
Yonsei University
2012
Baylor College of Medicine
2004
National Cerebral and Cardiovascular Center
2001
The University of Tokyo
1996
Ghrelin, an endogenous ligand for growth hormone secretagogue (GHS)receptor originally isolated from the stomach, occurs in hypothalamic arcuate nucleus and may play a role energy homeostasis. Synthetic GHSs have activated neurons containing neuropeptide Y (NPY),suggesting involvement of NPY some ghrelin actions. This study was designed to elucidate regulation food intake. A single intracerebroventricular (ICV) injection (5-5,000 ng/rat)caused significant dose-related increase cumulative...
To explore the pathophysiological role of leptin in obesity-related hypertension, we examined cardiovascular phenotypes transgenic skinny mice whose elevated plasma concentrations are comparable to those seen obese subjects. We also studied genetically KKAy with hyperleptinemia, which hypothalamic melanocortin system is antagonized by ectopic expression agouti protein. Systolic blood pressure (BP) and urinary catecholamine excretion relative nontransgenic littermates. The BP elevation...
Recent epidemiological studies indicate that obesity increases the incidence of depression. We examined implication leptin for obesity-associated Leptin induced antidepressive behavior in normal mice a forced swimming test (FST), and leptin-overexpressing transgenic with hyperleptinemia exhibited more FST than nontransgenic mice. In contrast, leptin-deficient ob/ob showed severe depressive mice, administration substantially ameliorated this behavior. Diet-induced obese (DIO) fed high-fat...
Leptin is a powerful inhibitor of bone formation in vivo . This antiosteogenic function involves leptin binding to its receptors on ventromedial hypothalamic neurons, the autonomous nervous system and β-adrenergic osteoblasts. However, mechanisms whereby controls neurons remain unclear. In this study, we compared ability regulate body weight mass show that anorexigenic functions are affected by similar amounts leptin. Using knock-in LacZ locus, failed detect any synthesis central system....
Lipoatrophic diabetes is caused by a deficiency of adipose tissue and characterized severe insulin resistance, hypoleptinemia, hyperphagia. The A-ZIP/F-1 mouse (A-ZIPTg/+) model lipoatrophic resistant, hypoleptinemic, hyperphagic, shows hepatic steatosis. We have also produced transgenic “skinny” mice that overexpression leptin (LepTg/+) no adipocyte triglyceride stores, are hypophagic show increased sensitivity. To explore the pathophysiological therapeutic roles in diabetes, we crossed...
Lack of leptin is implicated in insulin resistance and other metabolic abnormalities generalized lipodystrophy; however, the efficacy, safety, underlying mechanisms leptin-replacement therapy patients with lipodystrophy remain unclear.Seven Japanese lipodystrophy, two acquired five congenital type, were treated physiological replacement dose recombinant during an initial 4-month hospitalization followed by outpatient follow-up for up to 36 months.The twice-daily injection dramatically...
Leptin is an adipocyte-derived blood-borne satiety factor that acts directly on the hypothalamus, thereby regulating food intake and energy expenditure. We have demonstrated hypothalamic arcuate nucleus (Arc) a primary site of effect leptin (Neurosci Lett 224:149-152, 1997). To explore pathway sympathetic activation leptin, we examined effects single intravenous or intracerebroventricular injection recombinant human catecholamine secretion in rats. also direct microinjection into...
Ghrelin is an acylated peptide, whose lipid modification essential for its biological activities. Previous studies demonstrated that it strongly stimulates GH release and has a potent orexigenic action. Meanwhile, there enough evidence showing feeding states influence plasma ghrelin levels. Fasting secretion, reduces In this study we examined the regulation of by fasting in genetically obese animals considering molecular forms. Plasma levels active form as well those total were reduced ob/ob...
Excess of body fat, or obesity, is a major health problem and confers higher risk cardiovascular metabolic disorders such as diabetes, hypertension, coronary heart disease. Leptin an adipocyte-derived satiety factor that plays important role in the regulation energy homeostasis, its synthesis secretion are markedly increased obese subjects. To explore consequences amount leptin on long-term basis vivo, we generated transgenic skinny mice with elevated plasma concentrations comparable to...
Induced pluripotent stem (iPS) cells were recently established from human fibroblasts. In the present study we investigated adipogenic differentiation properties of four iPS cell lines and compared them with those two embryonic (ES) lines. After 12 days embryoid body formation an additional 10 on Poly‐ l ‐ornithine fibronectin‐ coated dishes medium, exhibited lipid accumulation transcription adipogenesis‐related molecules such as C/EBPα, PPARγ2, leptin aP2. These results demonstrate that...
To understand the role of agouti-related protein (AGRP), an endogenous antagonist hypothalamic melanocortin receptor, in leptin action, we produced a full-length recombinant AGRP and examined its effect on satiety leptin. We also studied leptin's regulation mRNA expression. A single intracerebroventricular (i.c.v.) injection significantly increased cumulative food intake body weight dose-dependent manner rats. The leptin-induced inhibition was reversed by co-injection manner. Hypothalamic...
Excess or loss of body fat can be associated with infertility, suggesting that adequate mass is essential for proper reproductive function. Leptin an adipocyte-derived hormone involved in the regulation food intake and energy expenditure, its synthesis secretion are markedly increased obesity. Short-term administration leptin accelerates onset puberty normal mice corrects sterility leptin-deficient ob/ob mice. These findings suggest a role as endocrine signal between depots axis, but effect...
Recent studies have suggested that 5'AMP-activated protein kinase (AMPK) is activated in response to metabolic stresses, such as contraction, hypoxia, and the inhibition of oxidative phosphorylation, which leads insulin-independent glucose transport skeletal muscle. In present study, we hypothesized acute stress increases rate via an AMPK-mediated mechanism. When rat epitrochlearis muscles were isolated incubated vitro Krebs buffer containing agent H(2)O(2), AMPKalpha1 activity increased a...
Translation termination requires two codon-specific polypeptide release factors in prokaryotes and one omnipotent factor eukaryotes. Sequences of 17 different from eukaryotes were compared. The prokaryotic share residues split into seven motifs. Conservation many discrete, perhaps critical, amino acids is observed eukaryotic factors, as well the C-terminal portion elongation (EF) G. Given that domains EF-G interacts with ribosomes by mimicry a tRNA structure, pattern conservation may reflect...
The adipose tissue renin-angiotensin system (RAS) has been implicated in the pathophysiology of obesity and dysfunction tissue. However, neither regulation angiotensinogen (AGT) expression nor secretion tissue-derived AGT fully elucidated humans.Human subcutaneous abdominal (SAT) biopsies were performed for 46 subjects with a wide range body mass index (BMI). Considering mRNA level indices fat mass, amount (A-AGT-S) was estimated. Using mouse model weight reduction, plasma levels measured...
Rho-associated kinase (ROCK) regulates reorganization of actin cytoskeleton. During adipogenesis, the structure filamentous is converted from long stress fibers to cortical actin, suggesting that ROCK involved in adipogenesis. Two isoforms have been identified: ROCK-I and ROCK-II. However, pharmacological inhibitors cannot distinguish two isoforms. In present study, we examined role adipogenesis cytoskeleton using genetic approaches. Y-27632, which inhibits activity both isoforms, enhanced...
Carbonic anhydrase (CA) is involved in various physiological processes such as acid-base balance and transport of carbon dioxide ions. In this study, we have succeeded the isolation a novel CA from mouse kidney by use signal sequence trap method. It 337-amino acid polypeptide with calculated molecular mass 37.5 kDa, consisting putative amino-terminal sequence, domain, transmembrane short hydrophilic carboxyl terminus, which designated XIV.11The designation XIV for cloned protein Car14 gene...
The melanocortin-4 receptor (MC4R) is a member of the seven membrane-spanning G protein-coupled superfamily and signals through activation adenylyl cyclase. MC4R mutations are most common known monogenic cause human obesity. However, no such have been found in Japanese obese subjects. Here we report novel homozygous missense mutation (G98R) nondiabetic woman with severe early-onset obesity, which located its second transmembrane domain. Her birth weight was 3,360 g, she gained progressively...
Evidence has accumulated that some of the angiotensin II AT 1 receptor antagonists have insulin‐sensitizing property. We thus examined effect telmisartan on insulin action using 3T3‐L1 adipocytes. With standard differentiation inducers, a higher dose effectively facilitated preadipocytes. Treatment both differentiating adipocytes and fully differentiated with caused dose‐dependent increase in mRNA levels for PPARγ target genes such as aP2 adiponectin. By contrast, attenuated...
Obesity causes excess fat accumulation in white adipose tissues (WAT) and also other insulin-responsive organs such as the skeletal muscle, increasing risk for insulin resistance, which can lead to obesity-related metabolic disorders. Peroxisome proliferator-activated receptor-α (PPARα) is a master regulator of fatty acid oxidation whose activator known improve hyperlipidemia. However, molecular mechanisms underlying PPARα activator-mediated reduction adiposity improvement disorders are...