Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BRD7 deficiency leads to the development of obesity and hyperglycemia.

ABSTRACT: Obesity is a debilitating disease that has become a global epidemic. Although progress is being made, the underlying molecular mechanism by which obesity develops still remains elusive. Recently, we reported that the expression levels of bromodomain-containing protein 7 (BRD7) are significantly reduced in the liver of obese mice. However, it is not clear whether decreased levels of hepatic BRD7 are directly associated with the development of obesity and disturbance in glucose homeostasis. Here, using heterozygous BRD7 knockout and liver-specific BRD7 knockout mouse models, we report that reduced BRD7 levels lead to increased weight gain with little effect on glucose metabolism. On the other hand, upregulating BRD7 in the liver starting at an early age protects mice from gaining excessive weight and developing glucose intolerance and insulin resistance when challenged with a high-fat diet.

SUBMITTER: Lee JM

PROVIDER: S-EPMC6441051 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

BRD7 deficiency leads to the development of obesity and hyperglycemia.

Lee Junsik M JM Kim Yoo Y Salazar Hernández Mario Andrés MA Han Youngah Y Liu Renyan R Park Sang Won SW

Scientific reports 20190329 1

Obesity is a debilitating disease that has become a global epidemic. Although progress is being made, the underlying molecular mechanism by which obesity develops still remains elusive. Recently, we reported that the expression levels of bromodomain-containing protein 7 (BRD7) are significantly reduced in the liver of obese mice. However, it is not clear whether decreased levels of hepatic BRD7 are directly associated with the development of obesity and disturbance in glucose homeostasis. Here, ...[more]

PMID: 30926848

Similar Datasets

Obesity Leads to Tissue, but not Serum Vitamin A Deficiency.

Project description:Obesity negatively affects multiple metabolic pathways, but little is known about the impact of obesity on vitamin A (VA)[retinol (ROL)], a nutrient that regulates expression of genes in numerous pathways essential for human development and health. We demonstrate that obese mice, generated from a high fat diet (HFD) or by genetic mutations (i.e., ob/ob; db/db), have greatly reduced ROL levels in multiple organs, including liver, lungs, pancreas, and kidneys, even though their diets have adequate VA. However, obese mice exhibit elevated serum VA. Organs from obese mice show impaired VA transcriptional signaling, including reductions in retinoic acid receptor (RAR?, RAR?2 and RAR?) mRNAs and lower intracellular ROL binding protein Crbp1 (RBP1) levels in VA-storing stellate cells. Reductions in organ VA signaling in obese mice correlate with increasing adiposity and fatty liver (steatosis), while with weight loss VA levels and signaling normalize. Consistent with our findings in obese mice, we show that increasing severity of fatty liver disease in humans correlates with reductions in hepatic VA, VA transcriptional signaling, and Crbp1 levels in VA storing stellate cells. Thus, obesity causes a "silent" VA deficiency marked by reductions in VA levels and signaling in multiple organs, but not detected by serum VA.

| S-EPMC4629132 | biostudies-literature

PON2 Deficiency Leads to Increased Susceptibility to Diet-Induced Obesity.

Project description:(1) Background: Paraoxonase 2 (PON2) is a ubiquitously expressed protein localized to endoplasmic reticulum and mitochondria. Previous studies have shown that PON2 exhibits anti-oxidant and anti-inflammatory functions, and PON2-deficient (PON2-def) mice are more susceptible to atherosclerosis. Furthermore, PON2 deficiency leads to impaired mitochondrial function. (2) Methods: In this study, we examined the susceptibility of PON2-def mice to diet-induced obesity. (3) Results: After feeding of an obesifying diet, the PON2-def mice exhibited significantly increased body weight due to increased fat mass weight as compared to the wild-type (WT) mice. The increased adiposity was due, in part, to increased adipocyte hypertrophy. PON2-def mice had increased fasting insulin levels and impaired glucose tolerance after diet-induced obesity. PON2-def mice had decreased oxygen consumption and energy expenditure. Furthermore, the oxygen consumption rate of subcutaneous fat pads from PON2-def mice was lower compared to WT mice. Gene expression analysis of the subcutaneous fat pads revealed decreased expression levels of markers for beige adipocytes in PON2-def mice. (4) Conclusions: We concluded that altered systemic energy balance, perhaps due to decreased beige adipocytes and mitochondrial dysfunction in white adipose tissue of PON2-def mice, leads to increased obesity in these mice.

| S-EPMC6356528 | biostudies-literature

Pancreas-specific Sirt1-deficiency in mice compromises beta-cell function without development of hyperglycemia

Project description:Sirtuin 1 (Sirt1) has been reported to be a critical positive regulator of glucose-stimulated insulin secretion in pancreatic beta-cells. The effects on islet cells and blood glucose levels when Sirt1 is deleted specifically in the pancreas are still unclear.This study examined islet glucose responsiveness, blood glucose levels, pancreatic islet histology and gene expression in Pdx1-Cre;Sirt1(ex4F/F) mice that have loss of function and loss of expression of Sirt1 specifically in the pancreas. We found that in the Pdx1-Cre;Sirt1(ex4F/F) mice, the relative insulin positive area and the islet size distribution were unchanged. However, beta-cells were functionally impaired, presenting with lower glucose-stimulated insulin secretion. This defect was not due to a reduced expression of insulin but was associated with a decreased expression of the glucose transporter Slc2A2/Glut2 and of the Glucagon like peptide-1 receptor (Glp1r) as well as with a marked down regulation of endoplasmic reticulum (ER) chaperones that participate in the Unfolded Protein Response (UPR) pathway. Counter intuitively, the Sirt1-deficient mice did not develop hyperglycemia. Pancreatic polypeptide (PP) cells were the only other islet cells affected, with reduced numbers in the Sirt1-deficient pancreas. This study provides new mechanistic insights showing that beta-cell function in Sirt1-deficient pancreas is affected due to altered glucose sensing and deregulation of the UPR pathway. Interestingly, we uncover a context in which impaired beta-cell function is not accompanied by increased glycemia. This points to a unique compensatory mechanism. Given the reduction in PP, investigation of its role in the control of blood glucose is warranted. To uncover other Sirt1-regulated mechanisms, we performed a gene expression microarray analysis comparing pancreata from the 6 month old Sirt1âdeficient mice to their controls (n=3 per group).

2016-03-01 | E-GEOD-67239 | biostudies-arrayexpress

Pancreas-Specific Sirt1-Deficiency in Mice Compromises Beta-Cell Function without Development of Hyperglycemia.

Project description:Aims/hypothesisSirtuin 1 (Sirt1) has been reported to be a critical positive regulator of glucose-stimulated insulin secretion in pancreatic beta-cells. The effects on islet cells and blood glucose levels when Sirt1 is deleted specifically in the pancreas are still unclear.MethodsThis study examined islet glucose responsiveness, blood glucose levels, pancreatic islet histology and gene expression in Pdx1Cre; Sirt1ex4F/F mice that have loss of function and loss of expression of Sirt1 specifically in the pancreas.ResultsWe found that in the Pdx1Cre; Sirt1ex4F/F mice, the relative insulin positive area and the islet size distribution were unchanged. However, beta-cells were functionally impaired, presenting with lower glucose-stimulated insulin secretion. This defect was not due to a reduced expression of insulin but was associated with a decreased expression of the glucose transporter Slc2a2/Glut2 and of the Glucagon like peptide-1 receptor (Glp1r) as well as a marked down regulation of endoplasmic reticulum (ER) chaperones that participate in the Unfolded Protein Response (UPR) pathway. Counter intuitively, the Sirt1-deficient mice did not develop hyperglycemia. Pancreatic polypeptide (PP) cells were the only other islet cells affected, with reduced numbers in the Sirt1-deficient pancreas.Conclusions/interpretationThis study provides new mechanistic insights showing that beta-cell function in Sirt1-deficient pancreas is affected due to altered glucose sensing and deregulation of the UPR pathway. Interestingly, we uncovered a context in which impaired beta-cell function is not accompanied by increased glycemia. This points to a unique compensatory mechanism. Given the reduction in PP, investigation of its role in the control of blood glucose is warranted.

| S-EPMC4457418 | biostudies-literature

Deficiency of NPGPx, an oxidative stress sensor, leads to obesity in mice and human.

Project description:Elevated oxidative stress is closely associated with obesity. Emerging evidence shows that instead of being a consequence of obesity, oxidative stress may also contribute to fat formation. Nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase (NPGPx) is a conserved oxidative stress sensor/transducer and deficiency of NPGPx causes accumulation of reactive oxygen species (ROS). In this communication, we show that NPGPx was highly expressed in preadipocytes of adipose tissue. Deficiency of NPGPx promoted preadipocytes to differentiate to adipocytes via ROS-dependent dimerization of protein kinase A regulatory subunits and activation of CCAAT/enhancer-binding protein beta (C/EBP?). This enhanced adipogenesis was alleviated by antioxidant N-acetylcysteine (NAC). Consistently, NPGPx-deficient mice exhibited markedly increased fat mass and adipocyte hypertrophy, while treatment with NAC ablated these phenotypes. Furthermore, single nucleotide polymorphisms (SNPs) in human NPGPx gene, which correlated with lower NPGPx expression level in adipose tissue, were associated with higher body mass index (BMI) in several independent human populations. These results indicate that NPGPx protects against fat accumulation in mice and human via modulating ROS, and highlight the importance of targeting redox homeostasis in obesity management.

| S-EPMC3944459 | biostudies-literature

Pancreas-specific Sirt1-deficiency in mice compromises beta-cell function without development of hyperglycemia

2016-03-01 | GSE67239 | GEO

Deficiency of lipoprotein lipase in neurons modifies the regulation of energy balance and leads to obesity.

Project description:Free fatty acids (FFAs) suppress appetite when injected into the hypothalamus. To examine whether lipoprotein lipase (LPL), a serine hydrolase that releases FFAs from circulating triglyceride (TG)-rich lipoproteins, might contribute to FFA-mediated signaling in the brain, we created neuron-specific LPL-deficient mice. Homozygous mutant (NEXLPL-/-) mice were hyperphagic and became obese by 16 weeks of age. These traits were accompanied by elevations in the hypothalamic orexigenic neuropeptides, AgRP and NPY, and were followed by reductions in metabolic rate. The uptake of TG-rich lipoprotein fatty acids was reduced in the hypothalamus of 3-month-old NEXLPL-/- mice. Moreover, deficiencies in essential fatty acids in the hypothalamus were evident by 3 months, with major deficiencies of long-chain n-3 fatty acids by 12 months. These results indicate that TG-rich lipoproteins are sensed in the brain by an LPL-dependent mechanism and provide lipid signals for the central regulation of body weight and energy balance.

| S-EPMC3034302 | biostudies-literature

Longitudinal Associations of Toothbrushing With Obesity and Hyperglycemia.

Project description:BackgroundToothbrushing is a health-related lifestyle habit and has been reported to contribute not only to oral health but also to some parameters of general health; however, little research has been conducted to understand the association of the frequency and timing of toothbrushing with the development of comprehensive metabolic abnormalities, with consideration of oral health condition. In this study, using longitudinal data, we examined this association in Japanese adults, adjusting for periodontal condition.MethodsA 5-year longitudinal study was performed with 4,537 participants between 35 and 64 years old who underwent an annual dental examination in both 2003 and 2008. Data about toothbrushing habits and metabolic abnormalities, such as obesity, hyperglycemia, diabetes, hypertension, hypertriglyceridemia, and low levels of high-density lipoprotein-cholesterol, were analyzed using Poisson regression analysis.ResultsThe percentage of participants with a toothbrushing frequency ≤1 time/day was 29.4%, and that for those not brushing their teeth at night was 21.4%. The incidences of obesity and hyperglycemia after 5 years were 5.5% and 28.4%, respectively. A toothbrushing frequency ≤1 time/day was associated with development of obesity (prevalence rate ratio [PRR] 1.77; 95% confidence interval [CI], 1.12-2.80), after adjusting for periodontal condition and potential risk factors. A significant association between not brushing teeth at night and hyperglycemia (PRR 1.30; 95% CI, 1.02-1.66) was observed in participants with toothbrushing frequency of 1 time/day. No association was found between toothbrushing habits and other metabolic abnormalities.ConclusionsThis study suggests that toothbrushing habits are associated with the development of obesity and hyperglycemia.

| S-EPMC7661336 | biostudies-literature

Embigin deficiency leads to delayed embryonic lung development and high neonatal mortality in mice.

Project description:Embigin (Gp70), a receptor for fibronectin and an ancillary protein for monocarboxylate transporters, is known to regulate stem cell niches in sebaceous gland and bone marrow. Here, we show that embigin expression is at high level during early mouse embryogenesis and that embigin is essential for lung development. Markedly increased neonatal mortality of Emb-/- mice can be explained by the compromised lung maturation: in Emb-/- mice (E17.5) the number and the size of the small airways and distal airspace are significantly smaller, there are fewer ATI and ATII cells, and the alkaline phosphatase activity in amniotic fluid is lower. Emb-/- lungs show less peripheral branching already at E12.5, and embigin is highly expressed in lung primordium. Thus, embigin function is essential at early pseudoglandular stage or even earlier. Furthermore, our RNA-seq analysis and Ki67 staining results support the idea that the development of Emb-/- lungs is rather delayed than defected.

| S-EPMC10839689 | biostudies-literature

Glcci1 deficiency leads to proteinuria.

Project description:Unbiased transcriptome profiling and functional genomics approaches identified glucocorticoid-induced transcript 1 (GLCCI1) as being a transcript highly specific for the glomerulus, but its role in glomerular development and disease is unknown. Here, we report that mouse glomeruli express far greater amounts of Glcci1 protein compared with the rest of the kidney. RT-PCR and Western blotting demonstrated that mouse glomerular Glcci1 is approximately 60 kD and localizes to the cytoplasm of podocytes in mature glomeruli. In the fetal kidney, intense Glcci1 expression occurs at the capillary-loop stage of glomerular development. Using gene knockdown in zebrafish with morpholinos, morphants lacking Glcci1 function had collapsed glomeruli with foot-process effacement. Permeability studies of the glomerular filtration barrier in these zebrafish morphants demonstrated a disruption of the selective glomerular permeability filter. Taken together, these data suggest that Glcci1 promotes the normal development and maintenance of podocyte structure and function.

| S-EPMC3279996 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data