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https://www.readbyqxmd.com/read/28431377/metabolic-regulation-and-the-anti-obesity-perspectives-of-human-brown-fat
#1
REVIEW
Camilla Scheele, Søren Nielsen
Activation of brown adipose tissue (BAT) in adult humans increase glucose and fatty acid clearance as well as resting metabolic rate, whereas a prolonged elevation of BAT activity improves insulin sensitivity. However, substantial reductions in body weight following BAT activation has not yet been shown in humans. This observation raise the possibility for feedback mechanisms in adult humans in terms of a brown fat-brain crosstalk, possibly mediated by batokines, factors produced by and secreted from brown fat...
April 11, 2017: Redox Biology
https://www.readbyqxmd.com/read/28427098/opa1-in-lipid-metabolism-function-of-opa1-in-lipolysis-and-thermogenesis-of-adipocytes
#2
Dinh-Toi Chu, Yang Tao, Kjetil Taskén
OPA1 (Optic Atrophy 1) is a mitochondrial GTPase known to regulate fission of mitochondria. It was recently also shown to locate on lipid droplets in adipocytes where it functions as an A-kinase anchoring protein (AKAP) that mediates adrenergic control of lipolysis by facilitating PKA phosphorylation of perilipin (Plin1). In brown adipocytes indirect evidence support the notion that OPA1 regulation of fission serves to increase thermogenesis, which thereby contributes to dissipation of energy. In white adipocytes, OPA1 located on lipid droplets serves as a gatekeeper to control lipolysis induced by adrenergic agonists...
April 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28408241/maternal-retinoids-increase-pdgfr%C3%AE-progenitor-population-and-beige-adipogenesis-in-progeny-by-stimulating-vascular-development
#3
Bo Wang, Xing Fu, Xingwei Liang, Zhixiu Wang, Qiyuan Yang, Tiande Zou, Wei Nie, Junxing Zhao, Pengfei Gao, Mei-Jun Zhu, Jeanene M de Avila, Joseph Maricelli, Buel D Rodgers, Min Du
Maternal vitamin A intake varies but its impact on offspring metabolic health is unknown. Here we found that maternal vitamin A or retinoic acid (RA) administration expanded PDGFRα(+) adipose progenitor population in progeny, accompanied by increased blood vessel density and enhanced brown-like (beige) phenotype in adipose tissue, protecting offspring from obesity. Blockage of retinoic acid signaling by either BMS493 or negative RA receptor (RARαDN) over-expression abolished the increase in blood vessel density, adipose progenitor population, and beige adipogenesis stimulated by RA...
April 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28385602/svct-2-determines-the-sensitivity-to-ascorbate-induced-cell-death-in-cholangiocarcinoma-cell-lines-and-patient-derived-xenografts
#4
Changzheng Wang, Hongwei Lv, Wen Yang, Ting Li, Tian Fang, Guishuai Lv, Qin Han, Liwei Dong, Tianyi Jiang, Beige Jiang, Guangshun Yang, Hongyang Wang
Cholangiocarcinoma (CC) is a devastating malignancy with late diagnosis and poor response to conventional chemotherapy. Recent studies have revealed anti-cancer effect of vitamin C (l-ascorbic acid, ascorbate) in several types of cancer. However, the effect of l-ascorbic acid (AA) in CC remains elusive. Herein, we demonstrated that AA induced cytotoxicity in CC cells by generating intracellular reactive oxygen species (ROS), and subsequently DNA damage, ATP depletion, mTOR pathway inhibition. Moreover, AA worked synergistically with chemotherapeutic agent cisplatin to impair CC cells growth both in vitro and in vivo...
April 4, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28380374/mitochondrial-patch-clamp-of-beige-adipocytes-reveals-ucp1-positive-and-ucp1-negative-cells-both-exhibiting-futile-creatine-cycling
#5
Ambre M Bertholet, Lawrence Kazak, Edward T Chouchani, Marta G Bogaczyńska, Ishan Paranjpe, Gabrielle L Wainwright, Alexandre Bétourné, Shingo Kajimura, Bruce M Spiegelman, Yuriy Kirichok
Cold and other environmental factors induce "browning" of white fat depots-development of beige adipocytes with morphological and functional resemblance to brown fat. Similar to brown fat, beige adipocytes are assumed to express mitochondrial uncoupling protein 1 (UCP1) and are thermogenic due to the UCP1-mediated H(+) leak across the inner mitochondrial membrane. However, this assumption has never been tested directly. Herein we patch clamped the inner mitochondrial membrane of beige and brown fat to provide a direct comparison of their thermogenic H(+) leak (IH)...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28370281/new-insights-into-the-local-and-systemic-functions-of-sclerostin-regulation-of-quiescent-bone-lining-cells-and-beige-adipogenesis-in-peripheral-fat-depots
#6
Jesus Delgado-Calle, Teresita Bellido
No abstract text is available yet for this article.
March 29, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28368209/enhanced-cytotoxic-effect-of-camptothecin-nanosponges-in-anaplastic-thyroid-cancer-cells-in-vitro-and-in-vivo-on-orthotopic-xenograft-tumors
#7
Casimiro Luca Gigliotti, Benedetta Ferrara, Sergio Occhipinti, Elena Boggio, Giuseppina Barrera, Stefania Pizzimenti, Mirella Giovarelli, Roberto Fantozzi, Annalisa Chiocchetti, Monica Argenziano, Nausicaa Clemente, Francesco Trotta, Caterina Marchiò, Laura Annaratone, Renzo Boldorini, Umberto Dianzani, Roberta Cavalli, Chiara Dianzani
Anaplastic carcinoma of the thyroid (ATC) is a lethal human malignant cancer with median survival of 6 months. To date, no treatment has substantially changed its course, which makes urgent need for the development of novel drugs or novel formulations for drug delivery. Nanomedicine has enormous potential to improve the accuracy of cancer therapy by enhancing availability and stability, decreasing effective doses and reducing side effects of drugs. Camptothecin (CPT) is an inhibitor of DNA topoisomerase-I with several anticancer properties but has poor solubility and a high degradation rate...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28346411/the-cold-induced-lipokine-12-13-dihome-promotes-fatty-acid-transport-into-brown-adipose-tissue
#8
Matthew D Lynes, Luiz O Leiria, Morten Lundh, Alexander Bartelt, Farnaz Shamsi, Tian Lian Huang, Hirokazu Takahashi, Michael F Hirshman, Christian Schlein, Alexandra Lee, Lisa A Baer, Francis J May, Fei Gao, Niven R Narain, Emily Y Chen, Michael A Kiebish, Aaron M Cypess, Matthias Blüher, Laurie J Goodyear, Gökhan S Hotamisligil, Kristin I Stanford, Yu-Hua Tseng
Brown adipose tissue (BAT) and beige adipose tissue combust fuels for heat production in adult humans, and so constitute an appealing target for the treatment of metabolic disorders such as obesity, diabetes and hyperlipidemia. Cold exposure can enhance energy expenditure by activating BAT, and it has been shown to improve nutrient metabolism. These therapies, however, are time consuming and uncomfortable, demonstrating the need for pharmacological interventions. Recently, lipids have been identified that are released from tissues and act locally or systemically to promote insulin sensitivity and glucose tolerance; as a class, these lipids are referred to as 'lipokines'...
March 27, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28340549/long-term-in-vivo-monitoring-of-adult-derived-human-liver-stem-progenitor-cells-by-bioluminescence-imaging-pet-and-contrast-enhanced-ct
#9
Mei-Ju Hsu, Julie Prigent, Pierre-Edouard Dollet, Joachim Ravau, Lionel Larbanoix, Gaetan Van Simaeys, Anne Bol, Vincent Grégoire, Serge Goldman, Gisèle Deblandre, Mustapha Najimi, Etienne Sokal, Catherine Lombard
Adult-derived human liver stem/progenitor cells (ADHLSCs) have the potential to alleviate liver injury. However, the optimal delivery route and long-term biodistribution of ADHLSCs remains unclear. In this paper, we used a triple fusion reporter system to determine the kinetic differences in the biodistribution of ADHLSCs following intrasplenic (IS) and intrahepatic (IH) administration in SCID-beige mice. ADHLSCs were transduced with a lentiviral vector expressing a triple-fusion reporter comprising renilla luciferase, monomeric red fluorescent protein and truncated HSV-1 thymidine kinase...
March 24, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28338809/resveratrol-derivative-btm-0512-mitigates-obesity-by-promoting-beige-remodeling-of-subcutaneous-preadipocytes
#10
Qingqing Li, Kuansong Wang, Yipeng Ma, Chunxiang Qin, Changsheng Dong, Ping Jin, Yan Wu, Xiaoming Xiong, Niansheng Li, Changping Hu, Jun Peng, Zhichun Yang
Recent studies revealed that sirtuin 1 (SIRT1) is involved in the regulation of energy metabolism and its agonist resveratrol showed anti-obesity effect. This study aims to determine whether BTM-0512, a novel derivative of resveratrol, acts as an antagonist of obesity and to explore its possible mechanisms. High-fat diet (HFD)-induced obese mice were intragastrically administered with BTM-0512 (5, 10, and 20 mg/kg/day) or resveratrol (10 mg/kg/day). It was found that the body weight, Lee's index, ratio of visceral adipose tissue (VAT) to body weight, and blood glucose were significantly reduced in BTM-0512-treated mice when compared with those in mice treated with resveratrol...
February 24, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28324027/follistatin-targets-distinct-pathways-to-promote-brown-adipocyte-characteristics-in-brown-and-white-adipose-tissues
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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