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https://www.readbyqxmd.com/read/28324027/follistatin-targets-distinct-pathways-to-promote-brown-adipocyte-characteristics-in-brown-and-white-adipose-tissues
#1
Rajan Singh, Melissa Braga, Srinivasa T Reddy, Se-Jin Lee, Meher Parveen, Victor Grijalva, Laurent Vergnes, Shehla Pervin
We previously demonstrated that Fst expression is highest in brown adipose tissue (BAT) and skeletal muscle, but is also present at substantial levels in epididymal (Epi) and subcutaneous (SC) white adipose tissues (WAT). Fst promotes mouse brown preadipocyte differentiation and promotes browning during differentiation of mouse embryonic fibroblasts (MEFs). Fst-transgenic (Fst-Tg) mouse show significant increase in circulating Fst levels and increased brown adipose mass. BAT of Fst-Tg mice had increased expression of brown adipose-associated markers including uncoupling protein 1 (UCP1), PRDM16, PGC-1α and Glut4...
January 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28296255/breg-dependent-islet-transplant-tolerance-is-also-nk-cell-dependent
#2
Christian Schuetz, Kang Mi Lee, Ryan Scott, Lisa Kojima, Laura Washburn, Liye Liu, Wei-Hui Liu, Haley Tector, Ji Lei, Heidi Yeh, James Kim, James F Markmann
Immunologic tolerance to solid organ and islet cell grafts has been achieved in various rodent models using antibodies directed at CD45RB and Tim-1. We have shown that this form of tolerance depends on regulatory B-cells. To elucidate further the mechanism by which Bregs induce tolerance we investigated the requirement of NK and NKT cells in this model. To do so, hyperglycemic B6, μMT, Beige or CD1d(-/-) mice received Balb/c islet grafts and treatment with the tolerance inducing regimen consisting of anti-CD45RB and anti -TIM1...
March 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28270523/id1-promotes-obesity-by-suppressing-brown-adipose-thermogenesis-and-white-adipose-browning
#3
Mallikarjun Patil, Bal Krishan Sharma, Sawsan Elattar, Judith Chang, Shweta Kapil, Jinling Yuan, Ande Satyanarayana
Obesity results from increased energy intake or defects in energy expenditure. Brown adipose tissue (BAT) is specialized for energy expenditure, a process called adaptive thermogenesis. Peroxisome proliferator activated receptor γ coactivator 1α (PGC1α) controls BAT-mediated thermogenesis by regulating the expression of Ucp1 Inhibitor of differentiation 1 (Id1) is a helix-loop-helix transcription factor that plays important roles in cell proliferation and differentiation. Here, we demonstrate a novel function of Id1 in BAT thermogenesis and programming of beige adipocytes in white adipose tissue (WAT)...
March 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28270520/functional-human-beige-adipocytes-from-induced-pluripotent-stem-cells
#4
Anne-Claire Guénantin, Nolwenn Briand, Emilie Capel, Florent Dumont, Romain Morichon, Claire Provost, Francesca Stillitano, Dorota Jeziorowska, Jean-Pierre Siffroi, Roger J Hajjar, Bruno Fève, Jean-Sébastien Hulot, Philippe Collas, Jacqueline Capeau, Corinne Vigouroux
Activation of thermogenic beige adipocytes has recently emerged as a promising therapeutic target in obesity and diabetes. Relevant human models for beige adipocyte differentiation are essential to implement such therapeutic strategies. We report a straightforward and efficient protocol to generate functional human beige adipocytes from induced pluripotent stem cells (hiPSCs). Without overexpression of exogenous adipogenic genes, our method recapitulates an adipogenic developmental pathway through successive mesodermal and adipogenic progenitor stages...
March 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28254844/vegf-a-expressing-adipose-tissue-shows-rapid-beiging-enhanced-survival-after-transplantation-and-confers-il4-independent-metabolic-improvements
#5
Jiyoung Park, Min Kim, Kai Sun, Yu Aaron An, Xue Gu, Philipp E Scherer
Adipocyte-derived VEGF-A plays a crucial role in angiogenesis and contributes to adipocyte function and systemic metabolism, such as insulin resistance, chronic inflammation and beigeing of subcutaneous adipose tissue. Utilizing a doxycycline (Dox)-inducible adipocyte-specific VEGF-A overexpressing mouse model, we investigated the dynamics of local VEGF-A effects on tissue beiging of adipose tissue transplants. VEGF-A overexpression in adipocytes triggers angiogenesis. We also observe a rapid appearance of beige fat cells in subcutaneous white adipose tissue (sWATs) within as early as 2 days post induction of VEGF-A...
March 2, 2017: Diabetes
https://www.readbyqxmd.com/read/28250021/mast-cells-promote-seasonal-white-adipose-beiging-in-humans
#6
Brian S Finlin, Beibei Zhu, Amy L Confides, Philip M Westgate, Brianna D Harfmann, Esther E Dupont-Versteegden, Philip A Kern
Human subcutaneous white adipose tissue (SC WAT) increases the expression of beige adipocyte genes in the winter. Studies in rodents suggest that a number of immune mediators are important in the beiging response. Here we studied the seasonal beiging response in SC WAT from lean humans. We measured the gene expression of various immune cell markers and performed multivariate analysis of the gene expression data to identify genes that predict UCP1. IL4 and, unexpectedly, the mast cell marker CPA3 predicted UCP1 gene expression...
March 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28246203/mitochondrial-homeostasis-in-adipose-tissue-remodeling
#7
REVIEW
Svetlana Altshuler-Keylin, Shingo Kajimura
Mitochondrial homeostasis is regulated by a balance between mitochondrial biogenesis and degradation. Emerging evidence suggests that mitophagy, a selective form of autophagy that degrades mitochondria, plays a key role in the physiology and pathophysiology of mitochondria-enriched cells, such as brown and beige adipocytes. This review discusses findings regarding the roles of autophagy and mitophagy in cellular development, maintenance, and functions of metabolic organs, including adipose tissue, liver, and pancreas...
February 28, 2017: Science Signaling
https://www.readbyqxmd.com/read/28244053/using-thermogenic-beige-cells-to-identify-biologically-active-small-molecules-and-peptides
#8
Ling Wu, Bin Xu
Incorporating molecular libraries in chemical biology screenings in cultured cells has been successfully used for gene discovery in many cellular processes. It has the unique potential to uncover novel mechanisms of complex cellular biology through the screening of small molecules and protein biologics in relevant cell-based assays. Recent development in the understanding and generation of thermogenic adipocytes provides opportunities for potential anti-obesity therapeutics discovery. In this chapter, we describe screening methods using thermogenic beige cells to identify novel compounds and peptides that activate adipocyte thermogenesis...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28244044/genetic-mouse-models-the-powerful-tools-to-study-fat-tissues
#9
Xingxing Kong, Kevin W Williams, Tiemin Liu
Obesity and Type 2 diabetes (T2D) are associated with a variety of comorbidities that contribute to mortality around the world. Although significant effort has been expended in understanding mechanisms that mitigate the consequences of this epidemic, the field has experienced limited success thus far. The potential ability of brown adipose tissue (BAT) to counteract obesity and metabolic disease in rodents (and potentially in humans) has been a topical realization. Recently, there is also another thermogenic fat cell called beige adipocytes, which are located among white adipocytes and share similar activated responses to cyclic AMP as classical BAT...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28244040/isolation-of-immune-cells-from-adipose-tissue-for-flow-cytometry
#10
Jonathan R Brestoff
Beige and brown adipocytes are thermogenic cells essential for maintaining metabolic homeostasis within white adipose tissue (WAT) and brown adipose tissue (BAT), respectively. Emerging studies indicate that various immune cell types such as alternatively activated macrophages (AAMacs), eosinophils, and group 2 innate lymphoid cells (ILC2s) critically regulate beige and/or brown adipocyte development and activation to protect against obesity and maintain core body temperature. These findings suggest that studies of beige and brown adipose tissue may benefit from traditional immunologic approaches such as flow cytometry of immune cells residing within WAT and BAT...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28244039/immuno-magnetic-isolation-and-thermogenic-differentiation-of-white-adipose-tissue-progenitor-cells
#11
Rohollah Babaei, Irem Bayindir-Buchhalter, Irina Meln, Alexandros Vegiopoulos
Appropriate cell models are necessary for the investigation of thermogenic beige adipocyte differentiation from progenitor cells. Here, we describe a primary cell culture method that is based on defined progenitor cells from murine white adipose tissue and aims at minimizing confounding factors including cell heterogeneity and nonphysiological differentiation inducers. Adipocyte progenitor cells are enriched by immuno-magnetic separation, expanded minimally, and induced for beige adipocyte differentiation with carbaprostacyclin, a stable analogue of the endogenous mediator PGI2...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28244038/flow-cytometric-isolation-and-differentiation-of-adipogenic-progenitor-cells-into-brown-and-brite-beige-adipocytes
#12
Jochen Steinbring, Antonia Graja, Anne-Marie Jank, Tim J Schulz
Aside from mature adipocytes, adipose tissue harbors several distinct cell populations including immune cells, endothelial cells, and adipogenic progenitor cells (AdPCs). AdPCs represent the reservoir of regenerative cells that replenishes adipocytes during normal cellular turnover and during times of increased demand for triglyceride-storage capacity. The worldwide increase in pathologies associated with the metabolic syndrome, such as obesity and type-2 diabetes, has heightened public and scientific interest in adipose tissues and the cell biological processes of adipose tissue formation and function...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28244037/flow-cytometry-assisted-isolation-of-adipose-tissue-derived-stem-cells
#13
Umesh D Wankhade, Sushil G Rane
Adipose tissue dysfunction is typically seen in metabolic diseases, particularly obesity and diabetes. White adipocytes store fat while brown adipocyte dissipates it via thermogenesis. In addition, beige adipocytes develop in white fat depots in response to stimulation of β-adrenergic pathways. It appears that the three types of adipocytes-white, brown, and beige-can be formed de novo from stem/precursor cells or via transdifferentiation. Identifying the presumptive progenitors that harbor capacity to differentiate to these distinct adipocyte cell types will enable their functional characterization...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28229360/thyroid-hormone-acting-via-tr%C3%AE-induces-expression-of-browning-genes-in-mouse-bone-marrow-adipose-tissue
#14
Richard C Lindsey, Subburaman Mohan
PURPOSE: Mutant hypothyroid mouse models have recently shown that thyroid hormone is critical for skeletal development during an important prepubertal growth period. Additionally, thyroid hormone negatively regulates total body fat, consistent with the well-established effects of thyroid hormone on energy and fat metabolism. Since bone marrow mesenchymal stromal cells differentiate into both adipocytes and osteoblasts and a relationship between bone marrow adipogenesis and osteogenesis has been predicted, we hypothesized thyroid hormone deficiency during the postnatal growth period increases marrow adiposity in mice...
February 22, 2017: Endocrine
https://www.readbyqxmd.com/read/28223294/the-%C3%AE-3-adrenergic-receptor-is-dispensable-for-browning-of-adipose-tissues
#15
Jasper M A de Jong, René T F Wouters, Nathalie Boulet, Barbara Cannon, Jan Nedergaard, Natasa Petrovic
Brown and brite/beige adipocytes are attractive therapeutic targets to treat metabolic diseases. To maximally utilize their functional potential, further understanding is required about their identities and their functional differences. Recent studies with β3-adrenergic receptor knockout mice reported that brite/beige adipocytes, but not classical brown adipocytes, require the β3-adrenergic receptor for cold-induced transcriptional activation of thermogenic genes. We aimed to further characterize this requirement of the β3-adrenergic receptor as a functional distinction between classical brown and brite/beige adipocytes...
February 21, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28223167/intracavitary-t4-immunotherapy-of-malignant-mesothelioma-using-pan-erbb-re-targeted-car-t-cells
#16
Astero Klampatsa, Daniela Y Achkova, David M Davies, Ana C Parente-Pereira, Natalie Woodman, James Rosekilly, Georgina Osborne, Thivyan Thayaparan, Andrea Bille, Michael Sheaf, James F Spicer, Juliet King, John Maher
Malignant mesothelioma remains an incurable cancer. We demonstrated that mesotheliomas expressed EGFR (79.2%), ErbB4 (49.0%) and HER2 (6.3%), but lacked ErbB3. At least one ErbB family member was expressed in 88% of tumors. To exploit ErbB dysregulation in this disease, patient T-cells were engineered by retroviral transduction to express a panErbB-targeted chimeric antigen receptor (CAR), co-expressed with a chimeric cytokine receptor that allows interleukin (IL)-4 mediated CAR T-cell proliferation. This combination is referred to as T4 immunotherapy...
February 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28220393/common-and-distinct-regulation-of-human-and-mouse-brown-and-beige-adipose-tissues-a-promising-therapeutic-target-for-obesity
#17
REVIEW
Xuejiao Liu, Christopher Cervantes, Feng Liu
Obesity, which underlies various metabolic and cardiovascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissipation...
February 20, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28214707/shortcuts-to-a-functional-adipose-tissue-the-role-of-small-non-coding-rnas
#18
REVIEW
Bruna B Brandão, Beatriz A Guerra, Marcelo A Mori
Metabolic diseases such as type 2 diabetes are a major public health issue worldwide. These diseases are often linked to a dysfunctional adipose tissue. Fat is a large, heterogenic, pleiotropic and rather complex tissue. It is found in virtually all cavities of the human body, shows unique plasticity among tissues, and harbors many cell types in addition to its main functional unit - the adipocyte. Adipose tissue function varies depending on the localization of the fat depot, the cell composition of the tissue and the energy status of the organism...
February 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/28197149/treatment-of-infantile-inflammatory-bowel-disease-and-autoimmunity-by-allogeneic-stem-cell-transplantation-in-lps-responsive-beige-like-anchor-deficiency
#19
Shahrzad Bakhtiar, Laura Gámez-Díaz, Andrea Jarisch, Jan Soerensen, Bodo Grimbacher, Bernd Belohradsky, Klaus-Michael Keller, Christoph Rietschel, Thomas Klingebiel, Sibylle Koletzko, Michael H Albert, Peter Bader
Inflammatory bowel disease (IBD) in young children can be a clinical manifestation of various primary immunodeficiency syndromes. Poor clinical outcome is associated with poor quality of life and high morbidity from the complications of prolonged immunosuppressive treatment and malabsorption. In 2012, mutations in the lipopolysaccharide-responsive beige-like anchor (LRBA) gene were identified as the cause of an autoimmunity and immunodeficiency syndrome. Since then, several LRBA-deficient patients have been reported with a broad spectrum of clinical manifestations without reliable predictive prognostic markers...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28178562/young-and-lean-elimination-of-senescent-cells-boosts-adaptive-thermogenesis
#20
Pablo J Fernandez-Marcos, Manuel Serrano
Thermogenesis converts the chemical energy of nutrients into heat, and this is associated to improved metabolic performance. In a previous issue of Cell Metabolism, Berry et al. (2017) reported that the progenitors of thermogenic beige adipocytes lose functionality with aging, and this process can be reversed with strategies that eliminate senescent cells.
February 7, 2017: Cell Metabolism
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