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https://www.readbyqxmd.com/read/27900258/adipocyte-specific-hypoxia-inducible-gene-2-promotes-fat-deposition-and-diet-induced-insulin-resistance
#1
Marina T DiStefano, Rachel J Roth Flach, Ozlem Senol-Cosar, Laura V Danai, Joseph V Virbasius, Sarah M Nicoloro, Juerg Straubhaar, Sezin Dagdeviren, Martin Wabitsch, Olga T Gupta, Jason K Kim, Michael P Czech
OBJECTIVE: Adipose tissue relies on lipid droplet (LD) proteins in its role as a lipid-storing endocrine organ that controls whole body metabolism. Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein in hepatocytes that promotes hepatic lipid storage, but its role in the adipocyte had not been investigated. Here we tested the hypothesis that Hig2 localization to LDs in adipocytes promotes adipose tissue lipid deposition and systemic glucose homeostasis. METHOD: White and brown adipocyte-deficient (Hig2(fl/fl) × Adiponection cre+) and selective brown/beige adipocyte-deficient (Hig2(fl/fl) × Ucp1 cre+) mice were generated to investigate the role of Hig2 in adipose depots...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27898069/clozapine-modifies-the-differentiation-program-of-human-adipocytes-inducing-browning
#2
E Kristóf, Q-M Doan-Xuan, A K Sárvári, Á Klusóczki, P Fischer-Posovszky, M Wabitsch, Z Bacso, P Bai, Z Balajthy, L Fésüs
Administration of second-generation antipsychotic drugs (SGAs) often leads to weight gain and consequent cardio-metabolic side effects. We observed that clozapine but not six other antipsychotic drugs reprogrammed the gene expression pattern of differentiating human adipocytes ex vivo, leading to an elevated expression of the browning marker gene UCP1, more and smaller lipid droplets and more mitochondrial DNA than in the untreated white adipocytes. Laser scanning cytometry showed that up to 40% of the differentiating single primary and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes had the characteristic morphological features of browning cells...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27895388/acetate-alters-expression-of-genes-involved-in-beige-adipogenesis-in-3t3-l1-cells-and-obese-kk-ay-mice
#3
Satoko Hanatani, Hiroyuki Motoshima, Yuki Takaki, Shuji Kawasaki, Motoyuki Igata, Takeshi Matsumura, Tatsuya Kondo, Takafumi Senokuchi, Norio Ishii, Junji Kawashima, Daisuke Kukidome, Seiya Shimoda, Takeshi Nishikawa, Eiichi Araki
The induction of beige adipogenesis within white adipose tissue, known as "browning", has received attention as a novel potential anti-obesity strategy. The expression of some characteristic genes including PR domain containing 16 is induced during the browning process. Although acetate has been reported to suppress weight gain in both rodents and humans, its potential effects on beige adipogenesis in white adipose tissue have not been fully characterized. We examined the effects of acetate treatment on 3T3-L1 cells and in obese diabetic KK-Ay mice...
November 2016: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/27889388/cellular-aging-contributes-to-failure-of-cold-induced-beige-adipocyte-formation-in-old-mice-and-humans
#4
Daniel C Berry, Yuwei Jiang, Robert W Arpke, Elizabeth L Close, Aki Uchida, David Reading, Eric D Berglund, Michael Kyba, Jonathan M Graff
Cold temperatures induce progenitor cells within white adipose tissue to form beige adipocytes that burn energy and generate heat; this is a potential anti-diabesity therapy. However, the potential to form cold-induced beige adipocytes declines with age. This creates a clinical roadblock to potential therapeutic use in older individuals, who constitute a large percentage of the obesity epidemic. Here we show that aging murine and human beige progenitor cells display a cellular aging, senescence-like phenotype that accounts for their age-dependent failure...
November 21, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27888588/lps-responsive-beige-like-anchor-gene-mutation-associated-with-possible-bronchiolitis-obliterans-organizing-pneumonia-associated-with-hypogammaglobulinemia-and-normal-igm-phenotype-and-low-number-of-b-cells
#5
Sima Shokri, Mohammad Nabavi, Tatjana Hirschmugl, Asghar Aghamohammadi, Saba Arshi, Mohamad Hassan Bemanian, Morteza Fallahpour, Rasool Molatefi, Mahsa Rekabi, Narges Eslami, Javad Ahmadian, Kian Darabi, Gholam Reza Sedighi, Maryam Monajemzadeh, Mohammadreza Modaresi, Nima Parvaneh, Kaan Boztug, Nima Rezaei
LPS-Responsive Beige-like Anchor (LRBA) deficiency is a disease which has recently been described in a group of patients with common variable immunodeficiency (CVID) in association with autoimmunity and/or inflammatory bowel disease (IBD)-like phenotype. We here describe a 10-year-old boy who experienced recurrent infections, mainly in the respiratory system, associated with thrombocytopenia and anemia. Immunological workup showed low numbers of B cells and low IgG, but normal IgM levels. In spite of therapeutic doses of antibiotics, antivirals, and antifungal agents, in addition to immunoglobulin replacement therapy, he developed disseminated involvement of both lungs with peripheral nodules; transbronchial lung biopsy revealed possible bronchiolitis obliterans organizing pneumonia (BOOP)...
October 2016: Acta Medica Iranica
https://www.readbyqxmd.com/read/27881733/lysosomal-trafficking-regulator-lyst-links-membrane-trafficking-to-toll-like-receptor-mediated-inflammatory-responses
#6
Andreas Westphal, Weijia Cheng, Jinbo Yu, Guntram Grassl, Martina Krautkrämer, Otto Holst, Niko Föger, Kyeong-Hee Lee
Subcellular compartmentalization of receptor signaling is an emerging principle in innate immunity. However, the functional integration of receptor signaling pathways into membrane trafficking routes and its physiological relevance for immune responses is still largely unclear. In this study, using Lyst-mutant beige mice, we show that lysosomal trafficking regulator Lyst links endolysosomal organization to the selective control of toll-like receptor 3 (TLR3)- and TLR4-mediated proinflammatory responses. Consequently, Lyst-mutant mice showed increased susceptibility to bacterial infection and were largely resistant to endotoxin-induced septic shock...
November 23, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27869309/roles-of-notch-signaling-in-adipocyte-progenitor-cells-and-mature-adipocytes
#7
REVIEW
Tizhong Shan, Jiaqi Liu, Weiche Wu, Ziye Xu, Yizhen Wang
Adipose tissues, composed with mature adipocytes and preadipocytic stromal/stem cells, play crucial roles in whole body energy metabolism and regenerative medicine. Mature adipocytes are derived and differentiated from mesenchymal stem cells (MSCs) or preadipocytes. This differentiation process, also called adipogenesis, is regulated by several signaling pathways and transcription factors. Notch1 signaling is a highly conserved pathway that is indispensable for stem cell hemostasis and tissue development. In adipocyte progenitor cells, Notch1 signaling regulates the adipogenesis process including proliferation and differentiation of the adipocyte progenitor cells in vitro...
November 21, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27866221/inter-organ-regulation-of-adipose-tissue-browning
#8
REVIEW
Simeng Wang, Xiaoyong Yang
Adaptive thermogenesis is an important component of energy expenditure. Brown adipocytes are best known for their ability to convert chemical energy into heat. Beige cells are brown-like adipocytes that arise in white adipose tissue in response to certain environmental cues to dissipate heat and improve metabolic homeostasis. A large body of intrinsic factors and external signals are critical for the function of beige adipocytes. In this review, we discuss recent advances in our understanding of neuronal, hormonal, and metabolic regulation of the development and activation of beige adipocytes, with a focus on the regulation of beige adipocytes by other organs, tissues, and cells...
November 19, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27855539/mouse-p2y4-nucleotide-receptor-is-a-negative-regulator-of-cardiac-adipose-derived-stem-cell-differentiation-and-cardiac-fat-formation
#9
Anne Lemaire, Marion Vanorlé, Michael Horckmans, Larissa di Pietrantonio, Sophie Clouet, Bernard Robaye, Jean-Marie Boeynaems, Didier Communi
Cardiac adipose-derived stem cells (cASCs) have the ability to differentiate into multiple cell lineages giving them a high potential for use in regenerative medicine. Cardiac fat tissue still raises many unsolved questions related to its formation and features. P2Y nucleotide receptors have already been described as regulators of differentiation of bone-marrow derived stem cells but remain poorly investigated in cASCs. We defined here the P2Y4 nucleotide receptor as a negative regulator of cardiac fat formation and cASC differentiation...
November 17, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27853148/the-lipid-sensor-gpr120-promotes-brown-fat-activation-and-fgf21-release-from-adipocytes
#10
Tania Quesada-López, Rubén Cereijo, Jean-Valery Turatsinze, Anna Planavila, Montserrat Cairó, Aleix Gavaldà-Navarro, Marion Peyrou, Ricardo Moure, Roser Iglesias, Marta Giralt, Decio L Eizirik, Francesc Villarroya
The thermogenic activity of brown adipose tissue (BAT) and browning of white adipose tissue are important components of energy expenditure. Here we show that GPR120, a receptor for polyunsaturated fatty acids, promotes brown fat activation. Using RNA-seq to analyse mouse BAT transcriptome, we find that the gene encoding GPR120 is induced by thermogenic activation. We further show that GPR120 activation induces BAT activity and promotes the browning of white fat in mice, whereas GRP120-null mice show impaired cold-induced browning...
November 17, 2016: Nature Communications
https://www.readbyqxmd.com/read/27849358/immune-modulation-of-brown-ing-adipose-tissue-in-obesity
#11
Susan M van den Berg, Andrea D van Dam, Patrick C N Rensen, Menno P J de Winther, Esther Lutgens
Obesity is associated with a variety of medical conditions such as type 2 diabetes and cardiovascular diseases and is therefore responsible for high morbidity and mortality rates. Increasing energy expenditure by brown adipose tissue (BAT) is a current novel strategy to reduce the excessive energy stores in obesity. Brown adipocytes burn energy to generate heat and are mainly activated upon cold exposure. As prolonged cold exposure is not a realistic therapy, researchers worldwide are searching for novel ways to activate BAT and/or induce beiging of WAT...
November 16, 2016: Endocrine Reviews
https://www.readbyqxmd.com/read/27824136/lrba-is-essential-for-allogeneic-responses-in-bone-marrow-transplantation
#12
Mi Young Park, Raki Sudan, Neetu Srivastava, Sudha Neelam, Christie Youngs, Jia-Wang Wang, Robert W Engelman, William G Kerr
The PH-BEACH-WD40 (PBW) protein family members play a role in coordinating receptor signaling and intracellular vesicle trafficking. LPS-Responsive-Beige-like Anchor (LRBA) is a PBW protein whose immune function remains elusive. Here we show that LRBA-null mice are viable, but exhibit compromised rejection of allogeneic, xenogeneic and missing self bone-marrow grafts. Further, we demonstrate that LRBA-null Natural Killer (NK) cells exhibit impaired signaling by the key NK activating receptors, NKp46 and NKG2D...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27766104/differential-role-of-adipose-tissues-in-obesity-and-related-metabolic-and-vascular-complications
#13
Almudena Gómez-Hernández, Nuria Beneit, Sabela Díaz-Castroverde, Óscar Escribano
This review focuses on the contribution of white, brown, and perivascular adipose tissues to the pathophysiology of obesity and its associated metabolic and vascular complications. Weight gain in obesity generates excess of fat, usually visceral fat, and activates the inflammatory response in the adipocytes and then in other tissues such as liver. Therefore, low systemic inflammation responsible for insulin resistance contributes to atherosclerotic process. Furthermore, an inverse relationship between body mass index and brown adipose tissue activity has been described...
2016: International Journal of Endocrinology
https://www.readbyqxmd.com/read/27760045/deficiency-of-base-excision-repair-enzyme-neil3-drives-increased-predisposition-to-autoimmunity
#14
Michel J Massaad, Jia Zhou, Daisuke Tsuchimoto, Janet Chou, Haifa Jabara, Erin Janssen, Salomé Glauzy, Brennan G Olson, Henner Morbach, Toshiro K Ohsumi, Klaus Schmitz, Markianos Kyriacos, Jennifer Kane, Kumiko Torisu, Yusaku Nakabeppu, Luigi D Notarangelo, Eliane Chouery, Andre Megarbane, Peter B Kang, Eman Al-Idrissi, Hasan Aldhekri, Eric Meffre, Masayuki Mizui, George C Tsokos, John P Manis, Waleed Al-Herz, Susan S Wallace, Raif S Geha
Alterations in the apoptosis of immune cells have been associated with autoimmunity. Here, we have identified a homozygous missense mutation in the gene encoding the base excision repair enzyme Nei endonuclease VIII-like 3 (NEIL3) that abolished enzymatic activity in 3 siblings from a consanguineous family. The NEIL3 mutation was associated with fatal recurrent infections, severe autoimmunity, hypogammaglobulinemia, and impaired B cell function in these individuals. The same homozygous NEIL3 mutation was also identified in an asymptomatic individual who exhibited elevated levels of serum autoantibodies and defective peripheral B cell tolerance, but normal B cell function...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27758866/mitochondrial-activity-in-human-white-adipocytes-is-regulated-by-the-ubiquitin-carrier-protein-9-microrna-30a-axis
#15
Eun Hee Koh, Yong Chen, David A Bader, Mark P Hamilton, Bin He, Brian York, Shingo Kajimura, Sean E McGuire, Sean M Hartig
The acquisition of beige adipocyte features by white fat cells corresponds to protection against obesity-induced metabolic diseases in humans and animal models of type 2 diabetes. In adipose tissue, expression of the E2 small ubiquitin-like modifier ligase ubiquitin carrier protein 9 (Ubc9) is positively correlated with markers of insulin resistance and corresponds with impaired browning of human white adipocytes. However, the molecular regulation of Ubc9 expression in adipocytes and other cells remains unclear...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27752996/pi3k-and-mapk-pathways-mediate-the-bdnf-trkb-increased-metastasis-in-neuroblastoma
#16
Zhongyan Hua, Xiao Gu, Yudi Dong, Fei Tan, Zhihui Liu, Carol J Thiele, Zhijie Li
Brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor TrkB have been reported to be associated with poor prognosis in neuroblastoma (NB) patients. Our previous studies indicated that BDNF activation of TrkB induces chemo-resistance through activation of phosphoinositide-3-kinase (PI3K)/Akt pathway. In this study, we investigated the role of BDNF/TrkB on metastasis in NB. A tetracycline-regulated TrkB-expressing NB cell line (TB3) was used. Scratch wound healing assay, Boyden chamber migration, and invasion assays were performed to study the migration and invasion of TB3 cells...
October 17, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27751202/invited-review-pre-and-postnatal-adipose-tissue-development-in-farm-animals-from-stem-cells-to-adipocyte-physiology
#17
I Louveau, M-H Perruchot, M Bonnet, F Gondret
Both white and brown adipose tissues are recognized to be differently involved in energy metabolism and are also able to secrete a variety of factors called adipokines that are involved in a wide range of physiological and metabolic functions. Brown adipose tissue is predominant around birth, except in pigs. Irrespective of species, white adipose tissue has a large capacity to expand postnatally and is able to adapt to a variety of factors. The aim of this review is to update the cellular and molecular mechanisms associated with pre- and postnatal adipose tissue development with a special focus on pigs and ruminants...
November 2016: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/27742571/regulation-of-brown-and-beige-fat-by-micrornas
#18
Yong Chen, Ruping Pan, Alexander Pfeifer
MicroRNAs (miRNAs) are small non-coding RNA molecules consisting of approximately 20 to 22 nucleotides. They play a very important role in the regulation of gene expression. miRNAs can be found in different species and a variety of organs and tissues including adipose tissue. There are two types of adipose tissue in mammals: White adipose tissue (WAT) is the largest energy storage, whereas brown adipose tissue (BAT) dissipates energy to maintain body temperature. BAT was first identified in hibernating animals and newborns as a defense against cold...
October 11, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27738055/a-novel-calcium-dependent-kinase-inhibitor-1517-cures-cryptosporidiosis-in-immunosuppressed-mice
#19
A Castellanos-Gonzalez, H Sparks, S Nava, W Huang, Z Zhang, K Rivas, M Hulverson, L Barrett, K K Ojo, E Fan, W C Van Voorhis, A C White
Cryptosporidium is recognized as one of the main causes of childhood diarrhea worldwide. However, the current treatment for cryptosporidiosis is suboptimal. Calcium flux is essential for entry in apicomplexan parasites. Calcium dependent protein kinases (CDPKs) are distinct from protein kinases of mammals, and the CDPK1 of the apicomplexan Cryptosporidium lack side-chains that typically block a hydrophobic pocket in protein kinases. We exploited this to develop bumped kinase inhibitors (BKI) that selectively target CDPK1...
October 12, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27704210/fat-tissues-the-brite-and-the-dark-sides
#20
Yong Chen, Ruping Pan, Alexander Pfeifer
Fat tissue is well known for its capacity to store energy and its detrimental role in obesity and metaflammation. However, humans possess different types of fat that have different functions in physiology and metabolic diseases. Apart from white adipose tissue (WAT), the body's main energy storage, there is also brown adipose tissue (BAT) that dissipates energy as a defense against cold and maintains energy balance for the whole body. BAT is present not only in newborns but also in adult humans and its mass correlates with leanness...
October 4, 2016: Pflügers Archiv: European Journal of Physiology
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