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https://www.readbyqxmd.com/read/28636934/the-tmao-producing-enzyme-flavin-containing-monooxygenase-3-regulates-obesity-and-the-beiging-of-white-adipose-tissue
#1
Rebecca C Schugar, Diana M Shih, Manya Warrier, Robert N Helsley, Amy Burrows, Daniel Ferguson, Amanda L Brown, Anthony D Gromovsky, Markus Heine, Arunachal Chatterjee, Lin Li, Xinmin S Li, Zeneng Wang, Belinda Willard, YongHong Meng, Hanjun Kim, Nam Che, Calvin Pan, Richard G Lee, Rosanne M Crooke, Mark J Graham, Richard E Morton, Carl D Langefeld, Swapan K Das, Lawrence L Rudel, Nizar Zein, Arthur J McCullough, Srinivasan Dasarathy, W H Wilson Tang, Bernadette O Erokwu, Chris A Flask, Markku Laakso, Mete Civelek, Sathyamangla V Naga Prasad, Joerg Heeren, Aldons J Lusis, Stanley L Hazen, J Mark Brown
Emerging evidence suggests that microbes resident in the human intestine represent a key environmental factor contributing to obesity-associated disorders. Here, we demonstrate that the gut microbiota-initiated trimethylamine N-oxide (TMAO)-generating pathway is linked to obesity and energy metabolism. In multiple clinical cohorts, systemic levels of TMAO were observed to strongly associate with type 2 diabetes. In addition, circulating TMAO levels were associated with obesity traits in the different inbred strains represented in the Hybrid Mouse Diversity Panel...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28626215/genetic-variation-in-the-obesity-gene-fto-is-not-associated-with-decreased-fat-oxidation-the-neo-study
#2
L L Blauw, R Noordam, S Trompet, J F P Berbée, F R Rosendaal, D van Heemst, K W van Dijk, D O Mook-Kanamori, R de Mutsert, P C N Rensen
BACKGROUND: The FTO gene harbours the strongest common genetic variant associated with obesity. Recently, rs1421085-T to -C substitution mapped in FTO was shown to induce a developmental shift of human adipocytes from an energy-combusting beige to an energy-storing white phenotype in vitro. As browning of adipocytes selectively enhances fat oxidation (FatOx), we hypothesized that rs1421085-C in FTO is associated with deceased FatOx compared with carbohydrate oxidation (CarbOx) and an increased respiratory quotient (RQ)...
June 19, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28624262/dibenzazepine-loaded-nanoparticles-induce-local-browning-of-white-adipose-tissue-to-counteract-obesity
#3
Chunhui Jiang, Mario Alberto Cano-Vega, Feng Yue, Liangju Kuang, Naagarajan Narayanan, Gozde Uzunalli, Madeline P Merkel, Shihuan Kuang, Meng Deng
Inhibition of Notch signaling via systemic drug administration triggers conversion of white adipocytes into beige adipocytes (browning) and reduces adiposity. However, translation of this discovery into clinical practice is challenged by potential off-target side effects and lack of control over the location and temporal extent of beige adipocyte biogenesis. Here, we demonstrate an alternative approach to stimulate browning using nanoparticles (NPs) composed of FDA-approved poly(lactide-co-glycolide) that enable sustained local release of a Notch inhibitor (dibenzazepine, DBZ)...
June 15, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28617554/the-study-on-specific-umbilical-blood-dc-vaccine-for-beige-nude-mice-loaded-human-colorectal-carcinoma-to-induce-anti-tumor-immunity
#4
Z-X Fu, J-S Han, F Liu, Z-L Zhao, D-B Li, L Shi, J-T Dong, Y Zhou, J-H Cai
OBJECTIVE: This study is to observe the immunosuppression of CD137L transfected umbilical blood Dcs (Dendritic cell) vaccine to tumor development of SCID/ Beige nude mice. MATERIALS AND METHODS: Samples of umbilical blood in the childbirth pregnant women were collected by density gradient centrifugation. Umbilical cord blood dendritic cells (Dcs) were transfected by specific CD137L via LipofectamineTM method and cells were harvested. Meanwhile, the peripheral blood of volunteers was collected to isolate Dcs, the Dcs were cultured for 5 days and hatched with SW-1116 cells antigen...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28611475/murine-lrba-deficiency-causes-ctla-4-deficiency-in-tregs-without-progression-to-immune-dysregulation
#5
Deborah Burnett, Ian Parish, Etienne Masle-Farquhar, Robert Brink, Christopher Goodnow
Inherited mutations in Lipopolysaccharide Responsive Beige-like Anchor (LRBA) cause a recessive human immune dysregulation syndrome with memory B cell and antibody deficiency (common variable immunodeficiency, CVID), inflammatory bowel disease, enlarged spleen and lymph nodes, accumulation of activated T cells, and multiple autoimmune diseases. To understand the pathogenesis of the syndrome, C57BL/6 mice carrying a homozygous truncating mutation in Lrba were produced using CRISPR/Cas9-mediated gene targeting...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28610025/a-new-species-of-the-genus-i-gracixalus-i-amphibia-anura-rhacophoridae-%C3%A2-from-mount-jinggang-southeastern-china
#6
Zhao-Chi Zeng, Jian Zhao, Chun-Quan Chen, Guo-Ling Chen, Zhong Zhang, Ying-Yong Wang
A new species, Gracixalus jinggangensis sp. nov., is described based on a series of specimens collected from Mount Jinggang, Jiangxi Province, southeastern China. The new species is distinguished from all other known congeners by the following combination of morphological characters: relatively small body size, SVL 27.9-33.8 mm in nine males and 31.6 mm in a single female; upper eyelid and dorsum lacking spines; skin of dorsal and lateral surface of head, body and limbs rough with sparsely scattered with tubercles; ventral skin granular; tibiotarsal projection absent; finger webbing rudimentary; toes with moderately developed webbing; brown to beige above in life, with an inverse Y-shaped dark brown marking extending from the interorbital region to the middle of dorsum; males with a single, subgular vocal sac, barely visible nuptial pads with minute granules on the dorsal surface of the bases of first and second fingers...
April 4, 2017: Zootaxa
https://www.readbyqxmd.com/read/28604703/cold-induced-conversion-of-cholesterol-to-bile-acids-in-mice-shapes-the-gut-microbiome-and-promotes-adaptive-thermogenesis
#7
Anna Worthmann, Clara John, Malte C Rühlemann, Miriam Baguhl, Femke-Anouska Heinsen, Nicola Schaltenberg, Markus Heine, Christian Schlein, Ioannis Evangelakos, Chieko Mineo, Markus Fischer, Maura Dandri, Claus Kremoser, Ludger Scheja, Andre Franke, Philip W Shaul, Joerg Heeren
Adaptive thermogenesis is an energy-demanding process that is mediated by cold-activated beige and brown adipocytes, and it entails increased uptake of carbohydrates, as well as lipoprotein-derived triglycerides and cholesterol, into these thermogenic cells. Here we report that cold exposure in mice triggers a metabolic program that orchestrates lipoprotein processing in brown adipose tissue (BAT) and hepatic conversion of cholesterol to bile acids via the alternative synthesis pathway. This process is dependent on hepatic induction of cytochrome P450, family 7, subfamily b, polypeptide 1 (CYP7B1) and results in increased plasma levels, as well as fecal excretion, of bile acids that is accompanied by distinct changes in gut microbiota and increased heat production...
June 12, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28601686/exaggerated-t-follicular-helper-cell-responses-in-lrba-deficiency-due-to-failure-of-ctla4-mediated-regulation
#8
Fayhan J Alroqi, Louis-Marie Charbonnier, Safa Baris, Ayca Kiykim, Janet Chou, Craig D Platt, Abdulrahman Algassim, Sevgi Keles, Bandar K Al Saud, Fowzan S Alkuraya, Michael Jordan, Raif S Geha, Talal A Chatila
PURPOSE: LRBA (lipopolysaccharide-responsive beige like anchor protein) and CTLA4 (cytotoxic T lymphocyte antigen 4) deficiencies give rise to overlapping phenotypes of immune dysregulation and autoimmunity, with dramatically increased frequencies of circulating T Follicular helper (cTFH) cells. We sought to determine the mechanisms of cTFH cell dysregulation in LRBA deficiency and the utility of monitoring cTFH cells as a correlate of clinical response to CTLA4-Ig therapy. METHODS: cTFH cells and other lymphocyte subpopulations were characterized...
June 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28593918/beyond-obesity-thermogenic-adipocytes-and-cardiometabolic-health
#9
Peter Aldiss, Neele Dellschaft, Harold Sacks, Helen Budge, Michael E Symonds
The global prevalence of obesity and related cardiometabolic disease continues to increase through the 21st century. Whilst multi-factorial, obesity is ultimately caused by chronic caloric excess. However, despite numerous interventions focussing on reducing caloric intake these either fail or only elicit short-term changes in body mass. There is now a focus on increasing energy expenditure instead which has stemmed from the recent 're-discovery' of cold-activated brown adipose tissue (BAT) in adult humans and inducible 'beige' adipocytes...
May 26, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28585199/adipose-tissue-function-and-expandability-as-determinants-of-lipotoxicity-and-the-metabolic-syndrome
#10
Stefania Carobbio, Vanessa Pellegrinelli, Antonio Vidal-Puig
The adipose tissue organ is organised as distinct anatomical depots located all along the body axis and it is constituted of three different types of adipocytes : white, beige and brown which are integrated with vascular, immune, neural and extracellular stroma cells. These distinct adipocytes serve different specialised functions. The main function of white adipocytes is to ensure healthy storage of excess nutrients/energy and its rapid mobilisation to supply the demand of energy imposed by physiological cues in other organs, whereas brown and beige adipocytes are designed for heat production through uncoupling lipid oxidation from energy production...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28571052/melioidosis-with-possible-haemophagocytic-lymphohistiocytosis
#11
Junaid Beig, Kerry Read, Darren Welch, Hasan Bhally
No abstract text is available yet for this article.
June 2, 2017: New Zealand Medical Journal
https://www.readbyqxmd.com/read/28562054/highly-selective-synthesis-of-dihydrobenzo-d-isoxazoles-and-dihydrobenzo-d-oxazoles-from-oximes-and-arynes-via-in-situ-generation-of-nitrones
#12
Tuanli Yao, Beige Ren, Bo Wang, Yanna Zhao
An efficient method for the synthesis of dihydrobenzo[d]isoxazoles and dihydrobenzo[d]oxazoles bearing a quaternary carbon center has been developed. The reaction involves generation of a ketonitrone intermediate in situ from a ketoxime and an aryne. A novel thermal rearrangement of the dihydrobenzo[d]isoxazole products to the corresponding dihydrobenzo[d]oxazoles has been observed. These transformations tolerate a variety of functional groups and offer a rapid and efficient way to diverse dihydrobenzo[d]isoxazoles and dihydrobenzo[d]oxazoles under mild transition-metal-free conditions...
May 31, 2017: Organic Letters
https://www.readbyqxmd.com/read/28547916/non-shivering-thermogenesis-as-a-mechanism-to-facilitate-sustainable-weight-loss
#13
REVIEW
B F Palmer, D J Clegg
Currently, there is a significant percentage of the population who are or will be classified as obese, necessitating novel strategies to facilitate sustainable weight loss. Reductions in basal metabolic rate occur in the face of weight loss and pose formidable barriers to individuals attempting to sustain meaningful weight reductions. Here, we discuss the mechanisms by which non-shivering thermogenesis may provide insight into metabolic pathways that can become druggable targets to facilitate sustainable weight loss...
May 25, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28543963/ageing-is-associated-with-brown-adipose-tissue-remodelling-and-loss-of-white-fat-browning-in-female-c57bl-6-mice
#14
Leidyanne Ferreira Gonçalves, Thaissa Queiroz Machado, Camila Castro-Pinheiro, Nathalia Guimaraes de Souza, Karen Jesus Oliveira, Caroline Fernandes-Santos
Fat storage changes throughout life and affects body metabolism. Ageing impact on brown (BAT) and white adipose tissue (WAT) deserves attention, especially in females, because they are less prone to age-induced weight gain. While in male mice the impact of ageing on adipose tissue remodelling is well characterized, the effects in female mice remain largely unclear. Thus, we investigated BAT and WAT remodelling during ageing in female C57BL/6 mice. At 3 months, body weight was 24 ± 0.3 g (mean±SD), and it increased from 6 to 9 months of age (+20%, P < 0...
May 24, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28538730/blocking-fsh-induces-thermogenic-adipose-tissue-and-reduces-body-fat
#15
Peng Liu, Yaoting Ji, Tony Yuen, Elizabeth Rendina-Ruedy, Victoria E DeMambro, Samarth Dhawan, Wahid Abu-Amer, Sudeh Izadmehr, Bin Zhou, Andrew C Shin, Rauf Latif, Priyanthan Thangeswaran, Animesh Gupta, Jianhua Li, Valeria Shnayder, Samuel T Robinson, Yue Eric Yu, Xingjian Zhang, Feiran Yang, Ping Lu, Yu Zhou, Ling-Ling Zhu, Douglas J Oberlin, Terry F Davies, Michaela R Reagan, Aaron Brown, T Rajendra Kumar, Solomon Epstein, Jameel Iqbal, Narayan G Avadhani, Maria I New, Henrik Molina, Jan B van Klinken, Edward X Guo, Christoph Buettner, Shozeb Haider, Zhuan Bian, Li Sun, Clifford J Rosen, Mone Zaidi
Menopause is associated with bone loss and enhanced visceral adiposity. A polyclonal antibody that targets the β-subunit of the pituitary hormone follicle-stimulating hormone (Fsh) increases bone mass in mice. Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr. The antibody also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue and enhances thermogenesis. These actions result from the specific binding of the antibody to the β-subunit of Fsh to block its action...
June 1, 2017: Nature
https://www.readbyqxmd.com/read/28536316/-adipose-stem-cell-system
#16
Yumiko Oishi, Ichiro Manabe
Adipose tissues are the major organ that controls systemic energy metabolism and maintain homeostasis by storing lipids, dissipating them as heat, and producing various adipokines. There are two major classes of adipocytes: white and brown adipocytes. White adipocytes store and release lipids, while brown adipocytes burn substrates to produce heat. In addition to classical brown adipose tissues consisting of brown adipocytes, cold exposure and β3 stimulation induce development of brown cell-like "beige" adipocytes in white adipose tissues...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28530121/glucocorticoids-retain-bi-potent-fibroblast-progenitors-during-alveolar-septation-in-mice
#17
Stephen E McGowan, Diann M McCoy
Glucocorticoids have been widely used and exert pleiotropic effects on alveolar structure and function, but do not improve the long-term clinical outcomes for patients with bronchopulmonary dysplasia, emphysema, or interstitial lung diseases. Treatments which foster alveolar regeneration could substantially improve the long-term outcomes for such patients. One approach to alveolar regeneration is to stimulate and guide intrinsic alveolar progenitors along developmental pathways used during secondary septation...
May 21, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28512785/clinical-immunological-molecular-analyses-and-outcomes-of-iranian-patients-with-lrba-deficiency-a-longitudinal-study
#18
Gholamreza Azizi, Hassan Abolhassani, Seyed Alireza Mahdaviani, Zahra Chavoshzadeh, Peyman Eshghi, Reza Yazdani, Fatemeh Kiaee, Mohammadreza Shaghaghi, Javad Mohammadi, Nima Rezaei, Lennart Hammarström, Asghar Aghamohammadi
BACKGROUND: LPS-responsive beige-like anchor protein (LRBA) deficiency is a combined immunodeficiency caused by mutation in LRBA gene. The patients have a variety of clinical symptoms including hypogammaglobulinemia, recurrent infections, autoimmunity and enteropathy. METHODS: A total of 17 LRBA-deficient patients were enrolled in this longitudinal study. For all patients, demographic information, clinical records, laboratory and molecular data were collected. RESULTS: Hypogammaglobulinemia were reported in 14 (82...
May 17, 2017: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/28507796/lyg1-exerts-antitumor-function-through-promoting-the-activation-proliferation-and-function-of-cd4-t-cells
#19
Huihui Liu, Yanfei Zhang, Zhengyang Liu, Pingzhang Wang, Xiaoning Mo, Weiwei Fu, Wanchang Liu, Yingying Cheng, Wenling Han
Identification of novel stimulatory cytokines with antitumor function would have great value in tumor immunotherapy investigations. Here, we report LYG1 (Lysozyme G-like 1) identified through the strategy of Immunogenomics as a novel classical secretory protein with tumor-inhibiting function. LYG1 recombinant protein (rhLYG1) could significantly suppress the growth of B16 tumors in WT B6 mice, but not in SCID-beige mice, Rag1(-/-) mice, CD4(+)- or CD8(+) T cell-deleted mice. It could increase the number of CD4(+) and CD8(+) T cells in tumor-infiltrating lymphocytes, tumor-draining lymph nodes, and spleens, and promote IFNγ production by T cells in tumor-bearing mice...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507197/muscle-adipose-tissue-cross-talk
#20
Kristin I Stanford, Laurie J Goodyear
Exercise training results in adaptations to both skeletal muscle and white adipose tissue (WAT) and protects against metabolic disorders including obesity and type 2 diabetes. Exercise-induced adaptations include an altered profile of secreted proteins, both myokines (from skeletal muscle) and adipokines (from adipose tissue). These secreted proteins may act in an endocrine manner to facilitate tissue-to-tissue communication and "cross talk," likely working together to improve overall metabolic health. Some studies suggest that contracting skeletal muscles release myokines that may function to alter the phenotype of WAT, including WAT "beiging," in which there is increased expression of beige marker genes and increased presence of multilocular cells within the WAT...
May 15, 2017: Cold Spring Harbor Perspectives in Medicine
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