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primary adipocyte diabetes

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https://www.readbyqxmd.com/read/29323267/scaffold-free-generation-of-uniform-adipose-spheroids-for-metabolism-research-and-drug-discovery
#1
Aloysius J Klingelhutz, Francoise A Gourronc, Anna Chaly, David A Wadkins, Anthony J Burand, Kathleen R Markan, Sharon O Idiga, Meng Wu, Matthew J Potthoff, James A Ankrum
Adipose tissue dysfunction is critical to the development of type II diabetes and other metabolic diseases. While monolayer cell culture has been useful for studying fat biology, 2D culture often does not reflect the complexity of fat tissue. Animal models are also problematic in that they are expensive, time consuming, and may not completely recapitulate human biology because of species variation. To address these problems, we have developed a scaffold-free method to generate 3D adipose spheroids from primary or immortal human or mouse pre-adipocytes...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317436/the-diabetes-gene-and-wnt-pathway-effector-tcf7l2-regulates-adipocyte-development-and-function
#2
Xi Chen, Ayala Iriscilla, Chris Shannon, Marcel Fourcaudot, Nikhil K Acharya, Christopher P Jenkinson, Sami Heikkinen, Luke Norton
The gene encoding for transcription factor 7-like 2 (TCF7L2) is the strongest type 2 diabetes (T2DM) candidate gene discovered to date. The TCF7L2 protein is a key transcriptional effector of the Wnt/β-catenin signaling pathway, which is an important developmental pathway that negatively regulates adipogenesis. However, the precise role that TCF7L2 plays in the development and function of adipocytes remains largely unknown. Using a combination of in vitro approaches, we first show that TCF7L2 protein is increased during adipogenesis in 3T3-L1 cells and primary adipocyte stem cells (ASC), and that TCF7L2 expression is required for the regulation of Wnt signaling during adipogenesis...
January 9, 2018: Diabetes
https://www.readbyqxmd.com/read/29283422/hyperglycemia-augments-the-adipogenic-transdifferentiation-potential-of-tenocytes-and-is-alleviated-by-cyclic-mechanical-stretch
#3
Yu-Fu Wu, Yu-Ting Huang, Hsing-Kuo Wang, Chung-Chen Jane Yao, Jui-Sheng Sun, Yuan-Hung Chao
Diabetes mellitus is associated with damage to tendons, which may result from cellular dysfunction in response to a hyperglycemic environment. Tenocytes express diminished levels of tendon-associated genes under hyperglycemic conditions. In contrast, mechanical stretch enhances tenogenic differentiation. However, whether hyperglycemia increases the non-tenogenic differentiation potential of tenocytes and whether this can be mitigated by mechanical stretch remains elusive. We explored the in vitro effects of high glucose and mechanical stretch on rat primary tenocytes...
December 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29237539/cdkn2a-deficiency-promotes-adipose-tissue-browning
#4
Nabil Rabhi, Sarah Anissa Hannou, Xavier Gromada, Elisabet Salas, Xi Yao, Frédérik Oger, Charlène Carney, Isabel C Lopez-Mejia, Emmanuelle Durand, Iandry Rabearivelo, Amélie Bonnefond, Emilie Caron, Lluis Fajas, Christian Dani, Philippe Froguel, Jean-Sébastien Annicotte
OBJECTIVES: Genome-wide association studies have reported that DNA polymorphisms at the CDKN2A locus modulate fasting glucose in human and contribute to type 2 diabetes (T2D) risk. Yet the causal relationship between this gene and defective energy homeostasis remains elusive. Here we sought to understand the contribution of Cdkn2a to metabolic homeostasis. METHODS: We first analyzed glucose and energy homeostasis from Cdkn2a-deficient mice subjected to normal or high fat diets...
December 1, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29167318/trail-reduces-impaired-glucose-tolerance-and-nafld-in-the-high-fat-diet-fed-mouse
#5
Stella Bernardi, Barbara Toffoli, Veronica Tisato, Fleur Bossi, Stefania Biffi, Andrea Lorenzon, Giorgio Zauli, Paola Secchiero, Bruno Fabris
AIMS/HYPOTHESIS: Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis-inducing ligand) may have an important role in the treatment of type 2 diabetes. It has been shown that TRAIL deficiency worsens diabetes and that TRAIL delivery, when it is given before disease onset, slows down its development. This study aimed at evaluating whether TRAIL had the potential to treat type 2 diabetes. METHODS: Thirty male C57BL/6J mice were randomized to a standard or a high-fat diet (HFD)...
November 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29155147/selective-and-membrane-permeable-small-molecule-inhibitors-of-nicotinamide-n-methyltransferase-reverse-high-fat-diet-induced-obesity-in-mice
#6
Harshini Neelakantan, Virginia Vance, Michael D Wetzel, Hua-Yu Leo Wang, Stanton F McHardy, Celeste C Finnerty, Jonathan D Hommel, Stanley J Watowich
There is a critical need for new mechanism-of-action drugs that reduce the burden of obesity and associated chronic metabolic comorbidities. A potentially novel target to treat obesity and type 2 diabetes is nicotinamide-N-methyltransferase (NNMT), a cytosolic enzyme with newly identified roles in cellular metabolism and energy homeostasis. To validate NNMT as an anti-obesity drug target, we investigated the permeability, selectivity, mechanistic, and physiological properties of a series of small molecule NNMT inhibitors...
November 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29097199/trpv4-is-involved-in-irisin-induced-endothelium-dependent-vasodilation
#7
Li Ye, Mengnan Xu, Min Hu, Hai Zhang, Xianming Tan, Qing Li, Bing Shen, Junhao Huang
Irisin, an exercise-induced myokine, induces conversion of white into brown adipocytes, promoting mitochondrial biogenesis and energy expenditure. Irisin has a vascular protective effect on endothelial function in animals, including humans. Defects in irisin signaling pathways result in endothelial dysfunction in obesity and diabetes. However, the mechanisms underlying the effects of irisin on endothelial function have not been elucidated. Transient receptor potential vanilloid subtype 4 (TRPV4) channels are one of the most important Ca(2+)-permeable cation channels in vascular endothelial cells...
October 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29046921/pioglitazone-reduces-cold-induced-brown-fat-glucose-uptake-despite-induction-of-browning-in-cultured-human-adipocytes-a-randomised-controlled-trial-in-humans
#8
Rebecca K C Loh, Melissa F Formosa, Nina Eikelis, David A Bertovic, Mitchell J Anderson, Shane A Barwood, Shane Nanayakkara, Neale D Cohen, Andre La Gerche, Anne T Reutens, Kenneth S Yap, Thomas W Barber, Gavin W Lambert, Martin H Cherk, Stephen J Duffy, Bronwyn A Kingwell, Andrew L Carey
AIMS/HYPOTHESIS: Increasing brown adipose tissue (BAT) activity is a possible therapeutic strategy to increase energy expenditure and glucose and lipid clearance to ameliorate obesity and associated comorbidities. The thiazolidinedione (TZD) class of glucose-lowering drugs increase BAT browning in preclinical experimental models but whether these actions extend to humans in vivo is unknown. The aim of this study was to determine the effect of pioglitazone treatment on adipocyte browning and adaptive thermogenesis in humans...
October 18, 2017: Diabetologia
https://www.readbyqxmd.com/read/29031721/cdkal1-a-type-2-diabetes-susceptibility-gene-regulates-mitochondrial-function-in-adipose-tissue
#9
Colin J Palmer, Raphael J Bruckner, Joao A Paulo, Lawrence Kazak, Jonathan Z Long, Amir I Mina, Zhaoming Deng, Katherine B LeClair, Jessica A Hall, Shangyu Hong, Peter-James H Zushin, Kyle L Smith, Steven P Gygi, Susan Hagen, David E Cohen, Alexander S Banks
OBJECTIVES: Understanding how loci identified by genome wide association studies (GWAS) contribute to pathogenesis requires new mechanistic insights. Variants within CDKAL1 are strongly linked to an increased risk of developing type 2 diabetes and obesity. Investigations in mouse models have focused on the function of Cdkal1 as a tRNA(Lys) modifier and downstream effects of Cdkal1 loss on pro-insulin translational fidelity in pancreatic β-cells. However, Cdkal1 is broadly expressed in other metabolically relevant tissues, including adipose tissue...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28885548/novel-insights-into-the-adipokinome-of-obese-and-obese-diabetic-mouse-models
#10
Birgit Knebel, Simon Goeddeke, Gereon Poschmann, Daniel F Markgraf, Sylvia Jacob, Ulrike Nitzgen, Waltraud Passlack, Christina Preuss, Hans-Dieter Dicken, Kai Stühler, Sonja Hartwig, Stefan Lehr, Jorg Kotzka
The group of adipokines comprises hundreds of biological active proteins and peptides released from adipose tissue. Alterations of those complex protein signatures are suggested to play a crucial role in the pathophysiology of multifactorial, metabolic diseases. We hypothesized that also the pathophysiology of type-2-diabetes is linked to the dysregulation of the adipocyte secretome. To test this, we investigated mouse models with monogenic defects in leptin signaling which are susceptible to adipositas (C57BL/6 Cg-Lep(ob) (obob)) or adipositas with diabetes (C57BL/KS Cg-Lepr(db) (dbdb)) according to their genetic background...
September 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28842503/the-c-terminal-fibrinogen-like-domain-of-angiopoietin-like-4-stimulates-adipose-tissue-lipolysis-and-promotes-energy-expenditure
#11
Allison E McQueen, Deepthi Kanamaluru, Kimberly Yan, Nora E Gray, Leslie Wu, Mei-Lan Li, Anthony Chang, Adeeba Hasan, Daniel Stifler, Suneil K Koliwad, Jen-Chywan Wang
Angptl4 (Angiopoietin-like 4) is a circulating protein secreted by white and brown adipose tissues and the liver. Structurally, Angptl4 contains an N-terminal coiled-coil domain (CCD) connected to a C-terminal fibrinogen-like domain (FLD) via a cleavable linker, and both full-length Angptl4 and its individual domains circulate in the bloodstream. Angptl4 inhibits extracellular lipoprotein lipase (LPL) activity and stimulates the lipolysis of triacylglycerol stored by adipocytes in the white adipose tissue (WAT)...
September 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28791439/metabolic-crosstalk-between-fatty-pancreas-and-fatty-liver-effects-on-local-inflammation-and-insulin-secretion
#12
Felicia Gerst, Robert Wagner, Gabriele Kaiser, Madhura Panse, Martin Heni, Jürgen Machann, Malte N Bongers, Tina Sartorius, Bence Sipos, Falko Fend, Christian Thiel, Silvio Nadalin, Alfred Königsrainer, Norbert Stefan, Andreas Fritsche, Hans-Ulrich Häring, Susanne Ullrich, Dorothea Siegel-Axel
AIMS/HYPOTHESIS: Obesity-linked ectopic fat accumulation is associated with the development of type 2 diabetes. Whether pancreatic and liver steatosis impairs insulin secretion is controversial. We examined the crosstalk of human pancreatic fat cells with islets and the role of diabetogenic factors, i.e. palmitate and fetuin-A, a hepatokine released from fatty liver. METHODS: Human pancreatic resections were immunohistochemically stained for insulin, glucagon, somatostatin and the macrophage/monocyte marker CD68...
November 2017: Diabetologia
https://www.readbyqxmd.com/read/28732776/rad-gtpase-is-essential-for-the-regulation-of-bone-density-and-bone-marrow-adipose-tissue-in-mice
#13
Catherine N Withers, Drew M Brown, Innocent Byiringiro, Matthew R Allen, Keith W Condon, Jonathan Satin, Douglas A Andres
The small GTP-binding protein Rad (RRAD, Ras associated with diabetes) is the founding member of the RGK (Rad, Rem, Rem2, and Gem/Kir) family that regulates cardiac voltage-gated Ca(2+) channel function. However, its cellular and physiological functions outside of the heart remain to be elucidated. Here we report that Rad GTPase function is required for normal bone homeostasis in mice, as Rad deletion results in significantly lower bone mass and higher bone marrow adipose tissue (BMAT) levels. Dynamic histomorphometry in vivo and primary calvarial osteoblast assays in vitro demonstrate that bone formation and osteoblast mineralization rates are depressed, while in vitro osteoclast differentiation is increased, in the absence of Rad...
October 2017: Bone
https://www.readbyqxmd.com/read/28720757/integrative-analyses-of-translatome-and-transcriptome-reveal-important-translational-controls-in-brown-and-white-adipose-regulated-by-micrornas
#14
David W Reid, Dan Xu, Peng Chen, Hongyuan Yang, Lei Sun
The epidemic of obesity and diabetes has markedly spurred the research interest in adipocyte biology. Brown adipocytes are specialized for energy expenditure and of therapeutic interest for treatment of metabolic diseases, but how brown adipocytes are distinguished from white adipocytes at the level of translational regulation remains poorly understood. To systemically determine the translational control of gene expression in adipose tissue, we performed ribosome profiling and RNA-seq in parallel to depict the translatome and transcriptome changes during primary brown and white adipogenesis, and between brown and white adipose tissue...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28628672/low-dose-exposure-to-bisphenols-a-f-and-s-of-human-primary-adipocyte-impacts-coding-and-non-coding-rna-profiles
#15
Marie Verbanck, Mickaël Canouil, Audrey Leloire, Véronique Dhennin, Xavier Coumoul, Loïc Yengo, Philippe Froguel, Odile Poulain-Godefroy
Bisphenol A (BPA) exposure has been suspected to be associated with deleterious effects on health including obesity and metabolically-linked diseases. Although bisphenols F (BPF) and S (BPS) are BPA structural analogs commonly used in many marketed products as a replacement for BPA, only sparse toxicological data are available yet. Our objective was to comprehensively characterize bisphenols gene targets in a human primary adipocyte model, in order to determine whether they may induce cellular dysfunction, using chronic exposure at two concentrations: a "low-dose" similar to the dose usually encountered in human biological fluids and a higher dose...
2017: PloS One
https://www.readbyqxmd.com/read/28583918/gpr120-suppresses-adipose-tissue-lipolysis-and-synergizes-with-gpr40-in-antidiabetic-efficacy
#16
Santhosh Satapati, Ying Qian, Margaret S Wu, Aleksandr Petrov, Ge Dai, Sheng-Ping Wang, Yonghua Zhu, Xiaolan Shen, Eric S Muise, Ying Chen, Emanuel Zycband, Adam Weinglass, Jerry Di Salvo, John S Debenham, Jason M Cox, Ping Lan, Vinit Shah, Stephen F Previs, Mark Erion, David E Kelley, Liangsu Wang, Andrew D Howard, Jin Shang
GPR40 and GPR120 are fatty acid sensors that play important roles in glucose and energy homeostasis. GPR40 potentiates glucose-dependent insulin secretion and demonstrated in clinical studies robust glucose lowering in type 2 diabetes. GPR120 improves insulin sensitivity in rodents, albeit its mechanism of action is not fully understood. Here, we postulated that the antidiabetic efficacy of GPR40 could be enhanced by coactivating GPR120. A combination of GPR40 and GPR120 agonists in db/db mice, as well as a single molecule with dual agonist activities, achieved superior glycemic control compared with either monotherapy...
August 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28534013/serum-from-pregnant-women-with-gestational-diabetes-mellitus-increases-the-expression-of-fabp4-mrna-in-primary-subcutaneous-human-pre-adipocytes
#17
Lan Li, Se Jin Lee, Song Yi Kook, Tae Gyu Ahn, Ji Yeon Lee, Jong Yun Hwang
OBJECTIVE: Gestational diabetes mellitus (GDM) is defined as glucose intolerance first detected during pregnancy. It can result in pregnancy complications such as birth injury, stillbirth. Fatty acid-binding protein 4 (FABP4), found in adipose tissue, is associated with insulin resistance, and type 2 diabetes. The aim of this study was to investigate whether FABP4 in the placenta and decidua of pregnant women with GDM is higher than that in normal pregnant women, and whether serum from pregnant women with GDM may cause adipocytes to secrete more FABP4 than does serum from a normal pregnant group...
May 2017: Obstetrics & Gynecology Science
https://www.readbyqxmd.com/read/28528355/increased-retinol-free-rbp4-contributes-to-insulin-resistance-in-gestational-diabetes-mellitus
#18
Yanmin Chen, Ping Lv, Mengkai Du, Zhaoxia Liang, Menglin Zhou, Danqing Chen
PURPOSE: Retinol-binding protein 4 (RBP4) is a circulating retinol transporter that is strongly associated with insulin resistance. The aim of this study was to evaluate the RBP4 and retinol level in rat model of gestational diabetes mellitus and the relationship between retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) and insulin resistance. METHODS: Pregnant rats were administered streptozotocin to induce diabetes. The RBP4 and retinol levels were evaluated in GDM and normal pregnant rats...
July 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28447068/microrna-21-is-up-regulated-in-adipose-tissue-of-obese-diabetic-subjects
#19
Valeria Guglielmi, Monica D'Adamo, Rossella Menghini, Marina Cardellini, Paolo Gentileschi, Massimo Federici, Paolo Sbraccia
We investigated miR21 expression in omental (OAT) and subcutaneous adipose tissue (SAT) from 16 obese subjects undergoing bariatric surgery. Patients were divided into two age- and BMI-matched groups according to the presence of type 2 diabetes (T2D). miR21 was not differently expressed in OAT and SAT. However, miR21 expression was two folds greater in adipose tissue in patients with T2D. Accordingly, in primary cultures of adipocytes from non diabetic overweight subjects, miR21 expression increased after 24-h exposure to high glucose and insulin...
March 31, 2017: Nutrition and Healthy Aging
https://www.readbyqxmd.com/read/28416283/activation-of-irf1-in-human-adipocytes-leads-to-phenotypes-associated-with-metabolic-disease
#20
Max Friesen, Raymond Camahort, Youn-Kyoung Lee, Fang Xia, Robert E Gerszten, Eugene P Rhee, Rahul C Deo, Chad A Cowan
The striking rise of obesity-related metabolic disorders has focused attention on adipocytes as critical mediators of disease phenotypes. To better understand the role played by excess adipose in metabolic dysfunction it is crucial to decipher the transcriptional underpinnings of the low-grade adipose inflammation characteristic of diseases such as type 2 diabetes. Through employing a comparative transcriptomics approach, we identified IRF1 as differentially regulated between primary and in vitro-derived genetically matched adipocytes...
May 9, 2017: Stem Cell Reports
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