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https://www.readbyqxmd.com/read/29764980/interplay-of-cell-cell-contacts-and-rhoa-mrtf-a-signaling-regulates-cardiomyocyte-identity
#1
Tatjana Dorn, Jessica Kornherr, Elvira I Parrotta, Dorota Zawada, Harold Ayetey, Gianluca Santamaria, Laura Iop, Elisa Mastantuono, Daniel Sinnecker, Alexander Goedel, Ralf J Dirschinger, Ilaria My, Svenja Laue, Tarik Bozoglu, Christian Baarlink, Tilman Ziegler, Elisabeth Graf, Rabea Hinkel, Giovanni Cuda, Stefan Kääb, Andrew A Grace, Robert Grosse, Christian Kupatt, Thomas Meitinger, Austin G Smith, Karl-Ludwig Laugwitz, Alessandra Moretti
Cell-cell and cell-matrix interactions guide organ development and homeostasis by controlling lineage specification and maintenance, but the underlying molecular principles are largely unknown. Here, we show that in human developing cardiomyocytes cell-cell contacts at the intercalated disk connect to remodeling of the actin cytoskeleton by regulating the RhoA-ROCK signaling to maintain an active MRTF/SRF transcriptional program essential for cardiomyocyte identity. Genetic perturbation of this mechanosensory pathway activates an ectopic fat gene program during cardiomyocyte differentiation, which ultimately primes the cells to switch to the brown/beige adipocyte lineage in response to adipogenesis-inducing signals...
May 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29758288/micrornas-in-brown-and-beige-fat
#2
REVIEW
Deborah Goody, Alexander Pfeifer
Brown adipose tissue (BAT) dissipates energy as heat and its activity correlates with leanness in human adults. Understanding the mechanisms behind the activation of BAT and the process of "browning", i.e. the appearance of inducible brown adipocytes called beige or brite (brown-in-white) cells in white adipose tissue (WAT), is of great interest for developing novel therapies to combat obesity. MicroRNAs (miRNAs) are small transcriptional regulators that control gene expression in a variety of tissues, including WAT and BAT...
May 11, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29757365/multifaceted-roles-of-beige-fat-in-energy-homeostasis-beyond-ucp1
#3
Carlos Henrique Sponton, Shingo Kajimura
Beige adipocytes are an inducible form of thermogenic adipose cells that emerge within the white adipose tissue in response to a variety of environmental stimuli, such as chronic cold acclimation. Similar to brown adipocytes that reside in brown adipose tissue (BAT) depots, beige adipocytes are also thermogenic; however beige adipocytes possess unique, distinguishing characteristics in their developmental regulation and biological function. This review highlights recent advances in our understanding of beige adipocytes, focusing on the diverse roles of beige fat in the regulation of energy homeostasis that are independent of the canonical thermogenic pathway via uncoupling protein 1 (UCP1)...
May 10, 2018: Endocrinology
https://www.readbyqxmd.com/read/29750960/a-novel-role-for-ptk2b-in-cultured-beige-adipocyte-differentiation
#4
Bin Ni, Jared S Farrar, Shanshan Chen, Joseph C Lownik, Francesco S Celi
Adipocyte differentiation is a tightly regulated process which requires the sequential and organized expression of numerous genes and proteins. Phosphorylation of cytoplasmic proteins and key transcription factors represents a critical regulatory mechanism of the process leading to adipocyte maturation and modulation of associated metabolic pathways. Despite the recognition of the importance of protein phosphorylation in adipocyte biology, relatively little is known about the role of specific kinases in thermogenic (brown or beige) adipocyte differentiation and function...
May 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29750781/metabolic-benefits-of-inhibition-of-p38%C3%AE-in-white-adipose-tissue-in-obesity
#5
Shengjie Zhang, Hongchao Cao, Yan Li, Yanyan Jing, Shengnan Liu, Cheng Ye, Hui Wang, Shuxian Yu, Chengyuan Peng, Lijian Hui, Yu-Cheng Wang, Haibing Zhang, Feifan Guo, Qiwei Zhai, Hui Wang, Ruimin Huang, Ling Zhang, Jingjing Jiang, Wei Liu, Hao Ying
p38 has long been known as a central mediator of protein kinase A (PKA) signaling in brown adipocytes, which positively regulate the transcription of uncoupling protein 1 (UCP-1). However, the physiological role of p38 in adipose tissues, especially the white adipose tissue (WAT), is largely unknown. Here, we show that mice lacking p38α in adipose tissues display a lean phenotype, improved metabolism, and resistance to diet-induced obesity. Surprisingly, ablation of p38α causes minimal effects on brown adipose tissue (BAT) in adult mice, as evident from undetectable changes in UCP-1 expression, mitochondrial function, body temperature (BT), and energy expenditure...
May 11, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29740429/rapid-flow-cytometry-based-test-for-the-diagnosis-of-lipopolysaccharide-responsive-beige-like-anchor-lrba-deficiency
#6
Laura Gámez-Díaz, Elena C Sigmund, Veronika Reiser, Werner Vach, Sophie Jung, Bodo Grimbacher
The diagnosis of lipopolysaccharide-responsive beige-like-anchor-protein (LRBA) deficiency currently relies on gene sequencing approaches that do not support a timely diagnosis and clinical management. We developed a rapid and sensitive test for clinical implementation based on the detection of LRBA protein by flow cytometry in peripheral blood cells after stimulation. LRBA protein was assessed in a prospective cohort of 54 healthy donors and 57 patients suspected of LRBA deficiency. Receiver operating characteristics analysis suggested an LRBA:MFI ratio cutoff point of 2...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29729716/diffuse-type-gastric-mucinous-and-signet-ring-cell-adenocarcinoma-in-a-captive-california-king-snake-lampropeltis-getula-californiae
#7
C-S Hsueh, W-T Li, C-R Jeng, V F Pang, H-W Chang
An adult female California king snake (Lampropeltis getula californiae) housed in Taipei Zoo was presented with a 2-week history of anorexia, fatigue and abdominal swelling. Exploratory laparotomy revealed a gastric mass with two circular perforations and multiple mottled white to beige protuberances along the mucosal surface. Histologically, the gastric mass showed an invasive, transmural growth of epithelial cells arranged in nests, lobules, acini and sheets in the mucosa and submucosa that progressively transformed into signet ring cells in the muscularis externa and subserosa...
April 2018: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/29719233/toward-an-understanding-of-how-immune-cells-control-brown-and-beige-adipobiology
#8
REVIEW
Francesc Villarroya, Rubén Cereijo, Joan Villarroya, Aleix Gavaldà-Navarro, Marta Giralt
Immune cells were recently found to have an unexpected involvement in controlling the thermogenic activity of brown and beige adipose tissue. Here, we review how macrophages, eosinophils, type 2 innate lymphoid cells, and T lymphocytes are linked to this process. In particular, the recruitment of alternatively activated macrophages and eosinophils is associated with brown fat activation and white fat browning. Conversely, pro-inflammatory immune cell recruitment represses the thermogenic activity of brown and beige adipose tissues via cytokines that inhibit noradrenergic signaling...
May 1, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29704660/genetic-and-epigenetic-control-of-adipose-development
#9
REVIEW
Olga Gulyaeva, Jon Dempersmier, Hei Sook Sul
White adipose tissue (WAT) is the primary energy storage organ and its excess contributes to obesity, while brown adipose tissue (BAT) and inducible thermogenic (beige/brite) adipocytes in WAT dissipate energy via Ucp1 to maintain body temperature. BAT and subcutaneous WAT develop perinatally while visceral WAT forms after birth from precursors expressing distinct markers, such as Myf5, Pref-1, Wt1, and Prx1, depending on the anatomical location. In addition to the embryonic adipose precursors, a pool of endothelial cells or mural cells expressing Pparγ, Pdgfrβ, Sma and Zfp423 may become adipocytes during WAT expansion in adults...
April 25, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29692364/mitophagy-controls-beige-adipocyte-maintenance-through-a-parkin-dependent-and-ucp1-independent-mechanism
#10
Xiaodan Lu, Svetlana Altshuler-Keylin, Qiang Wang, Yong Chen, Carlos Henrique Sponton, Kenji Ikeda, Pema Maretich, Takeshi Yoneshiro, Shingo Kajimura
Beige adipocytes are an inducible form of mitochondria-enriched thermogenic adipocytes that emerge in response to external stimuli, such as chronic cold exposure. We have previously shown that after the withdrawal of external stimuli, beige adipocytes directly acquire a white fat-like phenotype through autophagy-mediated mitochondrial degradation. We investigated the upstream pathway that mediates mitochondrial clearance and report that Parkin-mediated mitophagy plays a key role in the beige-to-white adipocyte transition...
April 24, 2018: Science Signaling
https://www.readbyqxmd.com/read/29692363/jak-tgf%C3%AE-cross-talk-links-transient-adipose-tissue-inflammation-to-beige-adipogenesis
#11
Rohollah Babaei, Maximilian Schuster, Irina Meln, Sarah Lerch, Rayane A Ghandour, Didier F Pisani, Irem Bayindir-Buchhalter, Julia Marx, Shuang Wu, Gabriele Schoiswohl, Adrian T Billeter, Damir Krunic, Jan Mauer, Yun-Hee Lee, James G Granneman, Lars Fischer, Beat P Müller-Stich, Ez-Zoubir Amri, Erin E Kershaw, Mathias Heikenwälder, Stephan Herzig, Alexandros Vegiopoulos
The transient activation of inflammatory networks is required for adipose tissue remodeling including the "browning" of white fat in response to stimuli such as β3-adrenergic receptor activation. In this process, white adipose tissue acquires thermogenic characteristics through the recruitment of so-called beige adipocytes. We investigated the downstream signaling pathways impinging on adipocyte progenitors that promote de novo formation of adipocytes. We showed that the Jak family of kinases controlled TGFβ signaling in the adipose tissue microenvironment through Stat3 and thereby adipogenic commitment, a function that was required for beige adipocyte differentiation of murine and human progenitors...
April 24, 2018: Science Signaling
https://www.readbyqxmd.com/read/29692362/transient-inflammatory-signaling-promotes-beige-adipogenesis
#12
REVIEW
Kai Sun, Zhanguo Gao, Mikhail G Kolonin
Inflammatory signaling has been implicated in adipose tissue remodeling and metabolism. In this issue of Science Signaling , Babaei et al report that lipolysis induced by β3-adrenergic signaling triggers transient inflammation that directs progenitor cells toward beige adipogenesis.
April 24, 2018: Science Signaling
https://www.readbyqxmd.com/read/29687396/isolation-and-differentiation-of-murine-primary-brown-beige-preadipocytes
#13
Hui Yu, Margo Emont, Heejin Jun, Jun Wu
Studies on thermogenic adipose cells (brown and beige fat) hold promise to treat obesity and its associated metabolic disorders due to the ability of these cells to dissipate energy in the form of heat. Although immortalized adipose cell lines have been widely used to investigate cell autonomous regulations, many physiological functions of thermogenic fat need to be studied with primary fat cells. Here, we present a detailed protocol of the isolation, culture, and differentiation of primary brown and beige preadipocytes from the stromal vascular fraction of murine interscapular and inguinal adipose depots...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29680372/inkt-cells-ameliorate-human-autoimmunity-lessons-from-alopecia-areata
#14
Amal Ghraieb, Aviad Keren, Alex Ginzburg, Yehuda Ullmann, Adam G Schrum, Ralf Paus, Amos Gilhar
Alopecia areata (AA) is understood to be a CD8+/NKG2D+ T cell-dependent autoimmune disease. Here, we demonstrate that human AA pathogenesis of is also affected by iNKT10 cells, an unconventional T cell subtype whose number is significantly increased in AA compared to healthy human skin. AA lesions can be rapidly induced in healthy human scalp skin xenotransplants on Beige-SCID mice by intradermal injections of autologous healthy-donor PBMCs pre-activated with IL-2. We show that in this in vivo model, the development of AA lesions is prevented by recognized the iNKT cell activator, α-galactosylceramide (α-GalCer), which stimulates iNKT cells to expand and produce IL-10...
April 18, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29678576/aging-impairs-beige-adipocyte-differentiation-of-mesenchymal-stem-cells-via-the-reduced-expression-of-sirtuin-1
#15
Vuong Cat Khanh, Amin Firman Zulkifli, Chiho Tokunaga, Toshiharu Yamashita, Yuji Hiramatsu, Osamu Ohneda
In the body, different types of adipose tissue perform different functions, with brown and beige adipose tissues playing unique roles in dissipating energy. Throughout life, adipocytes are regenerated from progenitors, and this process is impaired by aging. One of the progenitors of adipocytes are mesenchymal stem cells (MSCs), which have recently become a promising tool for stem cell therapy. However, whether or not aging impairs the brown/beige adipocyte differentiation of adipose tissue-derived MSCs (AT-MSCs) remains unclear...
April 17, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29657031/warming-induces-significant-reprogramming-of-beige-but-not-brown-adipocyte-cellular-identity
#16
Hyun Cheol Roh, Linus T Y Tsai, Mengle Shao, Danielle Tenen, Yachen Shen, Manju Kumari, Anna Lyubetskaya, Christopher Jacobs, Brian Dawes, Rana K Gupta, Evan D Rosen
Beige and brown adipocytes generate heat in response to reductions in ambient temperature. When warmed, both beige and brown adipocytes exhibit morphological "whitening," but it is unknown whether or to what extent this represents a true shift in cellular identity. Using cell-type-specific profiling in vivo, we uncover a unique paradigm of temperature-dependent epigenomic plasticity of beige, but not brown, adipocytes, with conversion from a brown to a white chromatin state. Despite this profound shift in cellular identity, warm whitened beige adipocytes retain an epigenomic memory of prior cold exposure defined by an array of poised enhancers that prime thermogenic genes for rapid response during a second bout of cold exposure...
April 5, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29618935/metabolic-profiling-of-follistatin-overexpression-a-novel-therapeutic-strategy-for-metabolic-diseases
#17
Rajan Singh, Shehla Pervin, Se-Jin Lee, Alan Kuo, Victor Grijalva, John David, Laurent Vergnes, Srinivasa T Reddy
Background: Follistatin (Fst) promotes brown adipocyte characteristics in adipose tissues. Methods: Abdominal fat volume (CT scan), glucose clearance (GTT test), and metabolomics analysis (mass spectrometry) of adipose tissues from Fst transgenic (Fst-Tg) and wild type (WT) control mice were analyzed. Oxygen consumption (Seahorse Analyzer) and lipidomics (gas chromatography) was analyzed in 3T3-L1 cells. Results: Fst-Tg mice show significant decrease in abdominal fat content, increased glucose clearance, improved plasma lipid profiles and significant changes in several conventional metabolites compared to the WT mice...
2018: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/29617639/adipose-tissue-flexes-its-muscles
#18
Sven Enerbäck
How brown and beige adipocytes activate UCP1-dependent thermogenesis has been studied in great detail. In Cell Metabolism, Tharp et al. (2018) have recently added another interesting dimension to this by demonstrating that actinomyosin-mediated elasticity regulates the thermogenic capacity of UCP1+ adipocytes, opening up new ways by which UCP1-dependent thermogenesis can be stimulated.
April 3, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29601828/identification-of-variants-in-ret-and-ihh-pathway-members-in-a-large-family-with-history-of-hirschsprung-disease
#19
Y Sribudiani, R K Chauhan, M M Alves, L Petrova, E Brosens, C Harrison, T Wabbersen, B M de Graaf, T Rügenbrink, G Burzynski, R W W Brouwer, W F J van IJcken, S M Maas, A de Klein, J Osinga, B J L Eggen, A J Burns, A S Brooks, I T Shepherd, R M W Hofstra
BACKGROUND & AIMS: Hirschsprung disease (HSCR) is an inherited congenital disorder characterized by absence of enteric ganglia in the distal part of the gut. Variants in ret proto-oncogene (RET) have been associated with up to 50% of familial and 35% of sporadic cases. We searched for variants that affect disease risk in a large, multi-generational family with history of HSCR in a linkage region previously associated with the disease (4q31.3-q32.3) and exome wide. METHODS: We performed exome sequencing analyses of a family in the Netherlands with 5 members diagnosed with HSCR and 2 members diagnosed with functional constipation...
March 27, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29563605/low-temperature-exposure-induces-browning-of-bone-marrow-stem-cell-derived-adipocytes-in-vitro
#20
Ksenija Velickovic, Hilda Anaid Lugo Leija, Ian Bloor, James Law, Harold Sacks, Michael Symonds, Virginie Sottile
Brown and beige adipocytes are characterised as expressing the unique mitochondrial uncoupling protein (UCP)1 for which the primary stimulus in vivo is cold exposure. The extent to which cold-induced UCP1 activation can also be achieved in vitro, and therefore perform a comparable cellular function, is unknown. We report an in vitro model to induce adipocyte browning using bone marrow (BM) derived mesenchymal stem cells (MSC), which relies on differentiation at 32 °C instead of 37 °C. The low temperature promoted browning in adipogenic cultures, with increased adipocyte differentiation and upregulation of adipogenic and thermogenic factors, especially UCP1...
March 21, 2018: Scientific Reports
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