A5010691279- Cholesterol and Lipid Metabolism
- Cancer, Lipids, and Metabolism
- Lipid metabolism and biosynthesis
- Peroxisome Proliferator-Activated Receptors
- Lipid metabolism and disorders
- Drug Transport and Resistance Mechanisms
- Lipoproteins and Cardiovascular Health
- Adipose Tissue and Metabolism
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Caveolin-1 and cellular processes
- Diet, Metabolism, and Disease
- Receptor Mechanisms and Signaling
- Regulation of Appetite and Obesity
- Glycosylation and Glycoproteins Research
- thermodynamics and calorimetric analyses
- Lung Cancer Treatments and Mutations
- Electrochemical sensors and biosensors
- Neuroendocrine Tumor Research Advances
- Cancer and biochemical research
- Liver Disease Diagnosis and Treatment
- Atherosclerosis and Cardiovascular Diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Pancreatic function and diabetes
- Chemical Synthesis and Analysis
- Lung Cancer Research Studies
Jichi Medical University
2002-2024
Jichi Medical University Hospital
2023-2024
The University of Tokyo
2013-2023
The University of Texas Southwestern Medical Center
2009-2019
University of Tokyo Hospital
2017
Okayama University
1958-2006
Fujita Animal Hospital
2006
University of Tsukuba
2001
National Cancer Center
1989
AbstractIn an attempt to identify transcription factors which activate sterol-regulatory element-binding protein 1c (SREBP-1c) transcription, we screened expression cDNA library from adipose tissue of SREBP-1 knockout mice using a reporter gene containing the 2.6-kb mouse promoter. We cloned and identified oxysterol receptors liver X receptor (LXRα) LXRβ as strong activators SREBP-1c In transfection studies, either LXRα or -β activated promoter-luciferase in dose-dependent manner. Deletion...
Previous studies have demonstrated that polyunsaturated fatty acids (PUFAs) suppress sterol regulatory element-binding protein 1c (SREBP-1c) expression and, thus, lipogenesis. In the current study, molecular mechanism for this suppressive effect was investigated with luciferase reporter gene assays using SREBP-1c promoter in HEK293 cells. Consistent previous data, addition of PUFAs to medium robustly inhibited activity. Deletion and mutation two liver X receptor (LXR)-responsive elements...
Recent studies on the in vivo roles of sterol regulatory element binding protein (SREBP) family indicate that SREBP-2 is more specific to cholesterogenic gene expression whereas SREBP-1 targets lipogenic genes. To define molecular mechanism involved this differential regulation, luciferase-reporter assays were performed HepG2 cells compare transactivities nuclear SREBP-1a, -1c, and -2 a battery SREBP-target promoters containing (SRE), SRE-like, or E-box sequences. The results show first...
Dietary polyunsaturated fatty acids (PUFA) are negative regulators of hepatic lipogenesis that exert their effects primarily at the level transcription. Sterol regulatory element-binding proteins (SREBPs) transcription factors responsible for regulation cholesterol, acid, and triglyceride synthesis. In particular, SREBP-1 is known to play a crucial role in lipogenic gene expression liver. To explore possible involvement suppression by PUFA, we challenged wild-type mice transgenic...
Abstract —Atherosclerotic coronary heart disease is a common complication of the insulin resistance syndrome that can occur with or without diabetes mellitus. Thiazolidinediones (TZDs), which are insulin-sensitizing antidiabetic agents, modulate development atherosclerosis not only by changing systemic metabolic conditions associated but also exerting direct effects on vascular wall cells express peroxisome proliferator–activated receptor-γ (PPAR-γ), nuclear receptor for TZDs. Here we show...
In the process of seeking sterol regulatory element-binding protein 1a (SREBP-1a) target genes, we identified and cloned a cDNA clone encoding mouse Δ5-desaturase (D5D). The hepatic expression D5D as well Δ6-desaturase (D6D) was highly activated in transgenic mice overexpressing nuclear SREBP-1a, -1c, -2. Disruption SREBP-1 gene significantly reduced both desaturases livers SREBP-1-deficient refed after fasting. downregulated by dietary PUFA, which were reported to suppress SREBP-1c...
Recent data suggest that sterol regulatory-binding protein (SREBP)-1c plays a key role in the transcriptional regulation of different lipogenic genes mediating lipid synthesis as regulator fuel metabolism. SREBP-1c regulates its downstream by changing own mRNA level, which led us to sequence and analyze promoter region mouse gene. A cluster putative binding sites several transcription factors composed an NF-Y site, E-box, sterol-regulatory element 3, Sp1 site were located at −90 base pairs...
Leptin-deficient mice (ob/ob) are an excellent murine model for obesity, insulin resistance, and diabetes, all of which components a multiple risk factor syndrome that, along with hypercholesterolemia, precipitates potential high atherosclerosis. In the current study, we show unexpectedly severe hyperlipidemia in ob/ob on background low density lipoprotein receptor (LDLR) deficiency (−/−). Doubly mutant (LDLR−/−;ob/ob) exhibited striking elevations both total plasma cholesterol (TC)...
The tumor suppressor p53 is a transcription factor that activates or represses its target genes after various genotoxic stresses. We have previously shown sterol regulatory element-binding protein-1 (SREBP-1), key transcriptional regulator of triglyceride synthesis, and the lipogenic enzymes under control are markedly suppressed in adipocytes from genetically obese ob/ob mice. Here we demonstrate highly induced mice fed state, leading to negative regulation SREBP-1 thereby genes. In fact,...
The mammalian enzyme involved in the final elongation of de novo fatty acid biosynthesis following building acids to 16 carbons by synthase has yet be identified. In process searching for genes activated sterol regulatory element-binding protein 1 (SREBP-1) using DNA microarray, we identified and characterized a murine cDNA clone that is highly similar acyl-CoA elongase gene family such as Cig30, Sscs, yeast ELOs. Studies on cells overexpressing full-length indicate encoded protein,...
Advanced glycation end products (AGEs) are nonenzymatically glycosylated proteins, which accumulate in vascular tissues aging and diabetes. Receptors for AGEs include scavenger receptors, recognize acetylated low density lipoproteins (Ac-LDL) such as receptor class AI/AII (SR-A), cell surface glycoprotein CD36, B type I (SR-BI), lectin-like oxidized lipoprotein receptor-1. The broad ligand repertoire of these receptors well the diversity have prompted us to examine whether also recognized by...
Insulin and glucose together have been previously shown to regulate hepatic sterol regulatory element-binding protein (SREBP)-1c expression. We sought explore the nutritional regulation of lipogenesis through SREBP-1c induction in a setting where effects sugars versus insulin could be distinguished. To do so, mice were depleted by streptozotocin (STZ) administration subjected fasting-refeeding protocol with glucose, fructose, or sucrose. Unexpectedly, insulin-depleted exhibited marked on all...
Acyl-CoA:cholesterol acyltransferase (ACAT) catalyzes esterification of cellular cholesterol. To investigate the role ACAT-1 in atherosclerosis, we have generated null (ACAT-1−/−) mice. ACAT activities were present liver and intestine but completely absent adrenal, testes, ovaries, peritoneal macrophages our ACAT-1−/− The mice had decreased openings eyes because atrophy meibomian glands, a modified form sebaceous glands normally expressing high activities. This phenotype is similar to dry...
<i>In vivo</i> studies suggest that sterol regulatory element-binding protein (SREBP)-1 plays a key role in the up-regulation of lipogenic genes livers animals have consumed excess amounts carbohydrates. In light this, we sought to use an established mouse hepatocyte cell line, H2-35, further define mechanism by which glucose regulates nuclear SREBP-1 levels. First, show these cells transcribe high levels SREBP-1c are increased 4-fold upon differentiation from prehepatocyte phenotype, making...
Obesity is a major health problem in industrialized societies, and fatty liver disease (hepatic steatosis) common obese individuals. Oxidative stress originating from increased intracellular levels of acids has been implicated as cause hepatocellular injury steatosis, although the precise mechanisms remain to be elucidated. p53, widely known tumor suppressor, shown often activated stressed cells, inducing cell cycle arrest or death. Here we demonstrate that p53 involved molecular associated...
Sterol regulatory element-binding protein (SREBP)-1c is now well established as a key transcription factor for the regulation of lipogenic enzyme genes such FAS in hepatocytes. Meanwhile, mechanisms gene adipocytes remain unclear. Here, we demonstrate that those are independent SREBP-1c. In adipocytes, unlike hepatocytes, stimulation SREBP-1c expression by liver X receptor agonist does not accompany upregulation, although nuclear concomitantly increased, indicating activation process...
Unstable lipid-rich plaques in atherosclerosis are characterized by the accumulation of macrophage foam cells loaded with cholesterol ester (CE). Although hormone-sensitive lipase and cholesteryl hydrolase (CEH) have been proposed to mediate hydrolysis CE macrophages, circumstantial evidence suggests presence other enzymes neutral (nCEH) activity. Here we show that murine orthologue KIAA1363, designated as (NCEH), is a microsomal nCEH high expression human macrophages. The effect various...
Hormone-sensitive lipase (HSL) is presumed to be essential for lipolysis, which defined as the mobilization of free fatty acids from adipocytes. In present study, we investigated effects various lipolytic hormones on lipolysis in adipocytes derived mouse embryonic fibroblasts (MEF adipocytes) prepared HSL-deficient mice (HSL−/−). HSL−/− MEF differentiated into mature a manner indistinguishable that wild-type mice. Both isoproterenol (ISO) and tumor necrosis factor (TNF)-α stimulated rate...