scholarly journals Association of genes with physiological functions by comparative analysis of pooled expression microarray data

2013 ◽  
Vol 45 (2) ◽  
pp. 69-78 ◽  
Author(s):  
Iuan-bor D. Chen ◽  
Vinay K. Rathi ◽  
Diana S. DeAndrade ◽  
Patrick Y. Jay
Keyword(s):  
Transcription Factor ◽  
Adipose Tissue ◽  
Regulatory Element ◽  
The Body ◽  
Accurate Identification ◽  
Physiological Functions ◽  
Microarray Expression Data ◽  
Multiple Organs ◽  
Brown Adipose ◽  
Sterol Regulatory Element

The physiological functions of a tissue in the body are carried out by its complement of expressed genes. Genes that execute a particular function should be more specifically expressed in tissues that perform the function. Given this premise, we mined public microarray expression data to build a database of genes ranked by their specificity of expression in multiple organs. The database permitted the accurate identification of genes and functions known to be specific to individual organs. Next, we used the database to predict transcriptional regulators of brown adipose tissue (BAT) and validated two candidate genes. Based upon hypotheses regarding pathways shared between combinations of BAT or white adipose tissue (WAT) and other organs, we identified genes that met threshold criteria for specific or counterspecific expression in each tissue. By contrasting WAT to the heart and BAT, the two most mitochondria-rich tissues in the body, we discovered a novel function for the transcription factor ESRRG in the induction of BAT genes in white adipocytes. Because the heart and other estrogen-related receptor gamma (ESRRG)-rich tissues do not express BAT markers, we hypothesized that an adipocyte co-regulator acts with ESRRG. By comparing WAT and BAT to the heart, brain, kidney and skeletal muscle, we discovered that an isoform of the transcription factor sterol regulatory element binding transcription factor 1 (SREBF1) induces BAT markers in C2C12 myocytes in the presence of ESRRG. The results demonstrate a straightforward bioinformatic strategy to associate genes with functions. The database upon which the strategy is based is provided so that investigators can perform their own screens.

Association of the PNPLA2, SCD1 and Leptin Expression with Fat Distribution in Liver and Adipose Tissue From Obese Subjects

2019 ◽  
Vol 128 (11) ◽  
pp. 715-722 ◽  
Author(s):  
Lucía De la Cruz-Color ◽  
Zamira Helena Hernández-Nazará ◽  
Montserrat Maldonado-González ◽  
Eliseo Navarro-Muñíz ◽  
José Alfredo Domínguez-Rosales ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Regulatory Element ◽  
The Body ◽  
Control Group ◽  
Histopathological Study ◽  
Abdominal Adiposity ◽  
Omental Adipose Tissue ◽  
Fat Depots ◽  
Fat Deposits ◽  
Sterol Regulatory Element

AbstractThe expansion of adipose tissue is regulated by insulin and leptin through sterol regulatory element-binding protein-1c (SREBP-1c), up-regulating lipogenesis in tissues by Stearoylcoenzyme A desaturase 1 (SCD1) enzyme, while adipose triglyceride lipase (ATGL) enzyme is key in lipolysis. The research objective was to evaluate the expression of Sterol Regulatory Element Binding Transcription Factor 1 (SREBF1), SCD1, Patatin Like Phospholipase Domain Containing 2 (PNPLA2), and leptin (LEP) genes in hepatic-adipose tissue, and related them with the increment and distribution of fat depots of individuals without insulin resistance. Thirty-eight subjects undergoing elective cholecystectomy with liver and adipose tissue biopsies (subcutaneous-omental) are included. Tissue gene expression was assessed by qPCR and biochemical parameters determined. Individuals are classified according to the body mass index, classified as lean (control group, n=12), overweight (n=11) and obesity (n=15). Abdominal adiposity was determined by anthropometric and histopathological study of the liver. Increased SCD1 expression in omental adipose tissue (p=0.005) and PNPLA2 in liver (p=0.01) were found in the obesity group. PNPLA2 decreased expression in subcutaneous adipose tissue was significant in individuals with abdominal adiposity (p=0.017). Anthropometric parameters positively correlated with liver PNPLA2 and the expression of liver PNPLA2 with serum leptin. SCD1 increased levels may represent lipid storage activity in omental adipose tissue. Liver PNPLA2 increased expression could function as a primary compensatory event of visceral fat deposits associated to the leptin hormone related to the increase of adipose tissue.

scholarly journals Emerging Roles for Serotonin in Regulating Metabolism: New Implications for an Ancient Molecule

2019 ◽  
Vol 40 (4) ◽  
pp. 1092-1107 ◽  
Author(s):  
Julian M Yabut ◽  
Justin D Crane ◽  
Alexander E Green ◽  
Damien J Keating ◽  
Waliul I Khan ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Drug Targets ◽  
Energy Homeostasis ◽  
De Novo ◽  
Nutrient Absorption ◽  
The Body ◽  
De Novo Lipogenesis ◽  
Nonalcoholic Fatty Liver ◽  
Multiple Organs ◽  
Brown Adipose

Abstract Serotonin is a phylogenetically ancient biogenic amine that has played an integral role in maintaining energy homeostasis for billions of years. In mammals, serotonin produced within the central nervous system regulates behavior, suppresses appetite, and promotes energy expenditure by increasing sympathetic drive to brown adipose tissue. In addition to these central circuits, emerging evidence also suggests an important role for peripheral serotonin as a factor that enhances nutrient absorption and storage. Specifically, glucose and fatty acids stimulate the release of serotonin from the duodenum, promoting gut peristalsis and nutrient absorption. Serotonin also enters the bloodstream and interacts with multiple organs, priming the body for energy storage by promoting insulin secretion and de novo lipogenesis in the liver and white adipose tissue, while reducing lipolysis and the metabolic activity of brown and beige adipose tissue. Collectively, peripheral serotonin acts as an endocrine factor to promote the efficient storage of energy by upregulating lipid anabolism. Pharmacological inhibition of serotonin synthesis or signaling in key metabolic tissues are potential drug targets for obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD).

scholarly journals Sterol regulatory element binding transcription factor 1 (SREBF1) polymorphism and milk fatty acid composition

2013 ◽  
Vol 96 (4) ◽  
pp. 2605-2616 ◽  
Author(s):  
R.A. Nafikov ◽  
J.P. Schoonmaker ◽  
K.T. Korn ◽  
K. Noack ◽  
D.J. Garrick ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Acid Composition ◽  
Regulatory Element ◽  
Milk Fatty Acid ◽  
Sterol Regulatory Element ◽  
Transcription Factor 1

scholarly journals Central Leptin Regulates Total Ceramide Content and Sterol Regulatory Element Binding Protein-1C Proteolytic Maturation in Rat White Adipose Tissue

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 169-178 ◽  
Author(s):  
Elena Bonzón-Kulichenko ◽  
Dominik Schwudke ◽  
Nilda Gallardo ◽  
Eduardo Moltó ◽  
Teresa Fernández-Agulló ◽  
...  
Keyword(s):  
Nervous System ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
White Adipose Tissue ◽  
Binding Protein ◽  
Regulatory Element ◽  
Mrna Levels ◽  
Element Binding Protein ◽  
Ceramide Content ◽  
Sterol Regulatory Element

Obesity and type 2 diabetes are associated with insulin and leptin resistance, and increased ceramide contents in target tissues. Because the adipose tissue has become a central focus in these diseases, and leptin-induced increases in insulin sensitivity may be related to effects of leptin on lipid metabolism, we investigated herein whether central leptin was able to regulate total ceramide levels and the expression of enzymes involved in ceramide metabolism in rat white adipose tissue (WAT). After 7 d central leptin treatment, the total content of ceramides was analyzed by quantitative shotgun lipidomics mass spectrometry. The effects of leptin on the expression of several enzymes of the sphingolipid metabolism, sterol regulatory element binding protein (SREBP)-1c, and insulin-induced gene 1 (INSIG-1) in this tissue were studied. Total ceramide levels were also determined after surgical WAT denervation. Central leptin infusion significantly decreased both total ceramide content and the long-chain fatty acid ceramide species in WAT. Concomitant with these results, leptin decreased the mRNA levels of enzymes involved in de novo ceramide synthesis (SPT-1, LASS2, LASS4) and ceramide production from sphingomyelin (SMPD-1/2). The mRNA levels of enzymes of ceramide degradation (Asah1/2) and utilization (sphingomyelin synthase, ceramide kinase, glycosyl-ceramide synthase, GM3 synthase) were also down-regulated. Ceramide-lowering effects of central leptin were prevented by local autonomic nervous system denervation of WAT. Finally, central leptin treatment markedly increased INSIG-1 mRNA expression and impaired SREBP-1c activation in epididymal WAT. These observations indicate that in vivo central leptin, acting through the autonomic nervous system, regulates total ceramide levels and SREBP-1c proteolytic maturation in WAT, probably contributing to improve the overall insulin sensitivity. Central leptin decreases total ceramide levels and prevents sterol regulatory element binding protein (SREBP-1C) proteolytic maturation in white adipose tissue, and probably, in this way, contributes to improve the overall insulin sensitivity.

scholarly journals Transcription Factor Sterol Regulatory Element Binding Protein 2 Regulates Scavenger Receptor Cla-1 Gene Expression

2004 ◽  
Vol 24 (12) ◽  
pp. 2358-2364 ◽  
Author(s):  
Morgan Tréguier ◽  
Chantal Doucet ◽  
Martine Moreau ◽  
Christiane Dachet ◽  
Joëlle Thillet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Binding Protein ◽  
Regulatory Element ◽  
Scavenger Receptor ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals Pharmacological myeloperoxidase (MPO) inhibition in an obese/hypertensive mouse model attenuates obesity and liver damage, but not cardiac remodeling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Arnold Piek ◽  
Debby P. Y. Koonen ◽  
Elisabeth-Maria Schouten ◽  
Eva L. Lindtstedt ◽  
Erik Michaëlsson ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mouse Model ◽  
The Body ◽  
Low Grade ◽  
Protective Effects ◽  
Positive Effects ◽  
Low Fat Diet ◽  
Multiple Organs ◽  
Cardiac Phenotype ◽  
Obesity Hypertension

AbstractLifestyle factors are important drivers of chronic diseases, including cardiovascular syndromes, with low grade inflammation as a central player. Attenuating myeloperoxidase (MPO) activity, an inflammatory enzyme associated with obesity, hypertension and heart failure, could have protective effects on multiple organs. Herein, the effects of the novel oral available MPO inhibitor AZM198 were studied in an obese/hypertensive mouse model which displays a cardiac phenotype. Eight week old male C57BL6/J mice received 16 weeks of high fat diet (HFD) combined with angiotensin II (AngII) infusion during the last 4 weeks, with low fat diet and saline infusion as control. Treated animals showed therapeutic AZM198 levels (2.1 µM), corresponding to 95% MPO inhibition. AZM198 reduced elevated circulating MPO levels in HFD/AngII mice to normal values. Independent of food intake, bodyweight increase and fat accumulation were attenuated by AZM198, alongside with reduced visceral adipose tissue (VAT) inflammation and attenuated severity of nonalcoholic steatohepatitis. The HFD/AngII perturbation caused impaired cardiac relaxation and contraction, and increased cardiac hypertrophy and fibrosis. AZM198 treatment did, however, not improve these cardiac parameters. Thus, AZM198 had positive effects on the main lipid controlling tissues in the body, namely adipose tissue and liver. This did, however, not directly result in improved cardiac function.

scholarly journals Wnt signaling mediates oncogenic synergy between Akt and Dlx5 in T-cell lymphomagenesis by enhancing cholesterol synthesis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yinfei Tan ◽  
Eleonora Sementino ◽  
Zemin Liu ◽  
Kathy Q. Cai ◽  
Joseph R. Testa
Keyword(s):  
Transcription Factor ◽  
T Cell ◽  
Cholesterol Synthesis ◽  
Regulatory Element ◽  
Cholesterol Biosynthesis ◽  
Homeobox Gene ◽  
Rna Seq ◽  
Expression Of Genes ◽  
Highly Sensitive ◽  
Sterol Regulatory Element

Abstract The Dlx5 homeobox gene was first implicated as an oncogene in a T-ALL mouse model expressing myristoylated (Myr) Akt2. Furthermore, overexpression of Dlx5 was sufficient to drive T-ALL in mice by directly activating Akt and Notch signaling. These findings implied that Akt2 cooperates with Dlx5 in T-cell lymphomagenesis. To test this hypothesis, Lck-Dlx5;Lck-MyrAkt2 transgenic mice were generated. MyrAkt2 synergized with Dlx5 to greatly accelerate and enhance the dissemination of T-lymphomagenesis. RNA-seq analysis performed on lymphomas from Lck-Dlx5;Lck-MyrAkt mice revealed upregulation of genes involved in the Wnt and cholesterol biosynthesis pathways. Combined RNA-seq and ChIP-seq analysis of lymphomas from Lck-Dlx5;Lck-MyrAkt mice demonstrated that β-catenin directly regulates genes involved in sterol regulatory element binding transcription factor 2 (Srebf2)-cholesterol synthesis. These lymphoma cells had high Lef1 levels and were highly sensitive to β-catenin and Srebf2-cholesterol synthesis inhibitors. Similarly, human T-ALL cell lines with activated NOTCH and AKT and elevated LEF1 levels were sensitive to inhibition of β-catenin and cholesterol pathways. Furthermore, LEF1 expression positively correlated with expression of genes involved in the cholesterol synthesis pathway in primary human T-ALL specimens. Together, these data suggest that targeting β-catenin and/or cholesterol biosynthesis, together with AKT, could have therapeutic efficacy in a subset of T-ALL patients.

scholarly journals Non-Viable Lactobacillus johnsonii JNU3402 Protects against Diet-Induced Obesity

Foods ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1494
Author(s):  
Garam Yang ◽  
Eunjeong Hong ◽  
Sejong Oh ◽  
Eungseok Kim
Keyword(s):  
Adipose Tissue ◽  
Body Weight Gain ◽  
Normal Diet ◽  
The Body ◽  
Peroxisome Proliferator ◽  
Lactobacillus Johnsonii ◽  
Peroxisome Proliferator Activated Receptor ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
And Function

In this study, the role of non-viable Lactobacillus johnsonii JNU3402 (NV-LJ3402) in diet-induced obesity was investigated in mice fed a high-fat diet (HFD). To determine whether NV-LJ3402 exhibits a protective effect against diet-induced obesity, 7-week-old male C57BL/6J mice were fed a normal diet, an HFD, or an HFD with NV-LJ3402 for 14 weeks. NV-LJ3402 administration was associated with a significant reduction in body weight gain and in liver, epididymal, and inguinal white adipose tissue (WAT) and brown adipose tissue weight in HFD-fed mice. Concomitantly, NV-LJ3402 administration to HFD-fed mice also decreased the triglyceride levels in the plasma and metabolic tissues and slightly improved insulin resistance. Furthermore, NV-LJ3402 enhanced gene programming for energy dissipation in the WATs of HFD-fed mice as well as in 3T3-L1 adipocytes with increased peroxisome proliferator-activated receptor-γ (PPARγ) transcriptional activity, suggesting that the PPARγ pathway plays a key role in mediating the anti-obesity effect of NV-LJ3402 in HFD-fed mice. Furthermore, NV-LJ3402 administration in HFD-fed mice enhanced mitochondrial levels and function in WATs and also increased the body temperature upon cold exposure. Together, these results suggest that NV-LJ3402 could be safely used to develop dairy products that ameliorate diet-induced obesity and hyperlipidemia.

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