Abstract:
:There has been great interest in the browning of fat for the treatment of obesity. Although β-lapachone (BLC) has potential therapeutic effects on obesity, the fat-browning effect and thermogenic capacity of BLC on obesity have never been demonstrated. Here, we showed that BLC stimulated the browning of white adipose tissue (WAT), increased the expression of brown adipocyte-specific genes (e.g., uncoupling protein 1 [UCP1]), decreased body weight gain, and ameliorated metabolic parameters in mice fed a high-fat diet. Consistently, BLC-treated mice showed significantly higher energy expenditure compared with control mice. In vitro, BLC increased the expression of brown adipocyte-specific genes in stromal vascular fraction-differentiated adipocytes. BLC also controlled the expression of miR-382, which led to the upregulation of its direct target, Dio2. Upregulation of miR-382 markedly inhibited the differentiation of adipocytes into beige adipocytes, whereas BLC recovered beige adipocyte differentiation and increased the expression of Dio2 and UCP1. Our findings suggest that the BLC-mediated increase in the browning of WAT and the thermogenic capacity of BAT significantly results in increases in energy expenditure. Browning of WAT by BLC was partially controlled via the regulation of miR-382 targeting Dio2 and may lead to the prevention of diet-induced obesity.
journal_name
Diabetesjournal_title
Diabetesauthors
Choi WH,Ahn J,Jung CH,Jang YJ,Ha TYdoi
10.2337/db15-1423subject
Has Abstractpub_date
2016-09-01 00:00:00pages
2490-501issue
9eissn
0012-1797issn
1939-327Xpii
db15-1423journal_volume
65pub_type
杂志文章相关文献
DIABETES文献大全abstract::Rats with chronic streptozotocin (SZ) diabetes develop dilatation of the alimentary tract, loss of fecal consistency, and autonomic neuropathy involving unmyelinated axons of the extrinsic innervation of the small bowel. Diabetic autonomic neuropathy involving the ileal mesenteric nerves is characterized by modest to ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.6.532
更新日期:1983-06-01 00:00:00
abstract:OBJECTIVE:Adipose tissue serves as an integrator of various physiological pathways, energy balance, and glucose homeostasis. Forkhead box-containing protein O subfamily (FoxO) 1 mediates insulin action at the transcriptional level. However, physiological roles of FoxO1 in adipose tissue remain unclear. RESEARCH DESIGN...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-0698
更新日期:2008-03-01 00:00:00
abstract:OBJECTIVE:Leukocyte infiltration of adipose is a critical determinant of obesity-related metabolic diseases. Fractalkine (CX3CL1) and its receptor (CX3CR1) comprise a chemokine system involved in leukocyte recruitment and adhesion in atherosclerosis, but its role in adipose inflammation and type 2 diabetes is unknown. ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0956
更新日期:2011-05-01 00:00:00
abstract::Using the hyperglycemic and euglycemic clamp, we demonstrated impaired β-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled β-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. β-Cell function parameters w...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1951
更新日期:2014-11-01 00:00:00
abstract:OBJECTIVE:Antecedent hypoglycemia can blunt neuroendocrine and autonomic nervous system responses to next-day exercise in type 1 diabetes. The aim of this study was to determine whether antecedent increase of plasma cortisol is a mechanism responsible for this finding. RESEARCH DESIGN AND METHODS:For this study, 22 ty...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db09-0382
更新日期:2009-09-01 00:00:00
abstract:OBJECTIVE:To ascertain the importance and mechanisms underlying the role of brain glucagon-like peptide (GLP)-1 in the control of metabolic and cardiovascular function. GLP-1 is a gut hormone secreted in response to oral glucose absorption that regulates glucose metabolism and cardiovascular function. GLP-1 is also pro...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-0121
更新日期:2008-10-01 00:00:00
abstract::A chromosome 1q25 variant (rs10911021) has been associated with coronary heart disease (CHD) in type 2 diabetes. In human umbilical vein endothelial cells (HUVECs), the risk allele "C" is associated with lower expression of the adjacent gene GLUL encoding glutamine synthase, converting glutamic acid to glutamine. To f...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0475
更新日期:2020-10-01 00:00:00
abstract::The inhibitory action of insulin and proinsulin on basal and glucagon-activated glycogenolysis was studied in cultured rat hepatocytes containing [14C]glycogen. Insulin or proinsulin given as sole hormones in the presence of 5 mM glucose decreased basal release of [14C]glucose from [14C]glycogen to 20%. Half-maximal e...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.36.5.551
更新日期:1987-05-01 00:00:00
abstract::Type 1 diabetes presents clinically with overt hyperglycemia resulting from progressive immune-mediated destruction of pancreatic β-cells and associated metabolic dysfunction. Combined genetic and immunological studies now highlight deficiencies in both the interleukin-2 (IL-2) receptor and its downstream signaling pa...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db11-1213
更新日期:2012-01-01 00:00:00
abstract::Recent evidence highlights the therapeutic potential of peroxisome proliferator-activated receptor-δ (PPARδ) agonists to increase insulin sensitivity in diabetes. However, the role of PPARδ in regulating vascular function is incompletely characterized. We investigate whether PPARδ activation improves endothelial funct...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-0117
更新日期:2012-12-01 00:00:00
abstract::Fasting hypoglycemia occurred in a patient with a histologically benign mesothelioma; the serum insulin was low (2-4 muU./ml.), as was the glucose utilization rate. Splanchnic glucose output was markedly decreased on direct measurement (21 mg./min.; normal: 108-180 mg./min.). Splanchnic uptake of gluconeogenic substra...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.25.3.202
更新日期:1976-03-01 00:00:00
abstract::Highly angiogenic bone marrow mononuclear cell-derived spheroids (BM-spheroids), formed by selective proliferation of the CD31+CD14+CD34+ monocyte subset via three-dimensional (3D) culture, have had robust angiogenetic capacity in rodent syngeneic renal subcapsular islet transplantation. We wondered whether the effica...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-0705
更新日期:2018-03-01 00:00:00
abstract::To clarify the relationship between abnormality of sorbitol and/or myo-inositol metabolism caused by hyperglycemia and diabetic macroangiopathy, we investigated the effects of high glucose concentrations and epalrestat, an aldose reductase inhibitor, on the metabolism of sorbitol and myo-inositol in cultured rabbit ao...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.11.1594
更新日期:1993-11-01 00:00:00
abstract::Near normal glucoregulation was maintained in 10 patients with insulin-dependent (type I) diabetes mellitus for 6 wk with preprogrammed continuous subcutaneous insulin infusion using a portable battery-powered infusion pump (CSII). This form of therapy resulted in a statistically significant increase in motor nerve co...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.29.8.668
更新日期:1980-08-01 00:00:00
abstract:OBJECTIVE:Zinc ions are essential for the formation of hexameric insulin and hormone crystallization. A nonsynonymous single nucleotide polymorphism rs13266634 in the SLC30A8 gene, encoding the secretory granule zinc transporter ZnT8, is associated with type 2 diabetes. We describe the effects of deleting the ZnT8 gene...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0551
更新日期:2009-09-01 00:00:00
abstract:OBJECTIVE:Progressive fibrosis in the diabetic kidney is driven and sustained by a diverse range of profibrotic factors. This study examines the critical role of microRNAs (miRNAs) in the regulation of the key fibrotic mediators, TGF-β1 and TGF-β2. RESEARCH DESIGN AND METHODS:Rat proximal-tubular epithelial cells (NRK...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0892
更新日期:2011-01-01 00:00:00
abstract::A significant increase in CO2 production, reflecting carbohydrate oxidation and/or fat synthesis, is observed in normal subjects after the ingestion of glucose. The anatomic site(s) of this CO2 production has not yet been localized, although liver and muscle are logical considerations. To assess the contribution of sk...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.10.960
更新日期:1985-10-01 00:00:00
abstract::Autoantibodies to glutamic acid decarboxylase (GAD) are frequent at or before the onset of insulin-dependent diabetes mellitus (IDDM). We have developed a simple, reproducible, and quantitative immunoprecipitation radioligand assay using as antigen in vitro transcribed and translated [35S]methionine-labeled human isle...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.3.459
更新日期:1994-03-01 00:00:00
abstract::The dysregulation of receptor tyrosine kinases (RTKs) in multiple cell types during chronic inflammation is indicative of their pathogenic role in autoimmune diseases. Among the many RTKs, vascular endothelial growth factor receptor (VEGFR) stands out for its multiple effects on immunity, vascularization, and cell mig...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-1619
更新日期:2013-08-01 00:00:00
abstract::The mechanisms of marked increase in plasma leptin soon after ventromedial hypothalamus (VMH) lesions were investigated. Although rats did not gain body weight or parametrial fat-pad mass 24 h after the operation, the acute VMH-lesioned rats exhibited substantial five- and fourfold increases in plasma leptin levels co...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.10.2034
更新日期:1999-10-01 00:00:00
abstract::Alzheimer disease and type 2 diabetes are characterized by increased prevalence with aging, a genetic predisposition, and comparable pathological features in the islet and brain (amyloid derived from amyloid beta protein in the brain in Alzheimer disease and islet amyloid derived from islet amyloid polypeptide in the ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.2.474
更新日期:2004-02-01 00:00:00
abstract::Obesity and family history of diabetes are both risk factors for non-insulin-dependent diabetes mellitus (NIDDM), but it has been proposed that lean individuals with NIDDM have a greater load of diabetes susceptibility genes. If this is the case, one might expect a high prevalence of NIDDM in relatives of diabetic ind...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.4.418
更新日期:1995-04-01 00:00:00
abstract::Current pharmacological options for type 2 diabetes do not cure the disease. Despite the availability of multiple drug classes that modulate glycemia effectively and minimize long-term complications, these agents do not reverse pathogenesis, and in practice they are not selected to correct the molecular profile specif...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/dbi16-0069
更新日期:2017-07-01 00:00:00
abstract::The anionic charge on the surface of the erythrocyte and the erythrocyte membrane content of sialic acid and acid glycosaminoglycans (GAGs) were evaluated in insulin-dependent diabetic patients who had albumin excretion rates less than 300 mg/24 h. In these subjects a statistically significant reduction of erythrocyte...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.6.745
更新日期:1988-06-01 00:00:00
abstract::Development of beta-cell lines for cell therapy of diabetes is hindered by functional deviations of the replicating cells from the normal beta-cell phenotype. In a recently developed cell line, denoted betaTC-tet, derived from transgenic mice expressing the SV40 T antigen (Tag) under control of the tetracycline (Tc) g...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.47.9.1419
更新日期:1998-09-01 00:00:00
abstract::The exposure of primary cultures of hepatocytes to insulin. 10(-8) M, for 16 h results in a decrease in high affinity insulin binding with no alterations in lower affinity binding. This is reflected in a decrease in the sensitivity, but normal responsiveness, of cultured hepatocytes to the acute effect of insulin on t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.2.145
更新日期:1982-02-01 00:00:00
abstract::It has been suggested that the hemodynamic derangements present in diabetic ketoacidosis are the results not only of profound volume depletion but also of the effects of increased production of vasodilating prostaglandins (PGs), principally PGI2, released by adipose tissue. In animal and in vitro models, prostaglandin...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diab.45.5.602
更新日期:1996-05-01 00:00:00
abstract::In humans, low levels of growth hormone (GH) and its mediator, IGF-1, associate with hepatic lipid accumulation. In mice, congenital liver-specific ablation of the GH receptor (GHR) results in reductions in circulating IGF-1 and hepatic steatosis, associated with systemic insulin resistance. Due to the intricate relat...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0649
更新日期:2016-12-01 00:00:00
abstract::The glycolytic enzyme glucokinase plays a primary role in the glucose-responsive secretion of insulin, and defects of this enzyme can cause NIDDM. As a step toward understanding the molecular basis of glucokinase (GK) gene regulation, we assessed the structure and regulation of the human GK gene beta-cell-type promote...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.11.1478
更新日期:1996-11-01 00:00:00
abstract::The development of autoimmune diabetes in NOD mice results from selective destruction of beta-cells by a T-cell-dependent autoimmune process. However, the mechanisms that control the generation of beta-cell cytotoxic T-cells in vivo are poorly understood. We recently established 8.3-T-cell receptor (TCR)-beta transgen...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.1.34
更新日期:1999-01-01 00:00:00