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Marie-Therese Rached, Steven J Millership, Silvia M A Pedroni, Agharul I Choudhury, Ana S H Costa, Darran G Hardy, Justyna A Glegola, Elaine E Irvine, Colin Selman, Megan C Woodberry, Vijay K Yadav, Sanjay Khadayate, Antonio Vidal-Puig, Samuel Virtue, Christian Frezza, Dominic J Withers
OBJECTIVE: Sympathetic nervous system and immune cell interactions play key roles in the regulation of metabolism. For example, recent convergent studies have shown that macrophages regulate obesity through brown adipose tissue (BAT) activation and beiging of white adipose tissue (WAT) via effects upon local catecholamine availability. However, these studies have raised issues about the underlying mechanisms involved including questions regarding the production of catecholamines by macrophages, the role of macrophage polarization state and the underlying intracellular signaling pathways in macrophages that might mediate these effects...
November 28, 2018: Molecular Metabolism
Sugata Hazra, Grant D Henson, R Colton Bramwell, Anthony J Donato, Lisa A Lesniewski
Blood flow regulation is a critical factor for tissue oxygenation and substrate supply. Increased reactivity of arteries to vasoconstrictors may increase vascular resistance, resulting in reduced blood flow. Here, we aimed to investigate the effect of high fat (HF) diet on stiffness and vasoconstrictor reactivity of white and brown adipose tissue (WAT and BAT) resistance arteries and also investigated the interconversion of both the adipose depots during HF diet condition. Vasoconstrictor reactivity,passive morphology and mechanical properties of arteries from B6D2F1 mice(5 month) fed a normal chow (NC) or HF diet (8 weeks) were measured using pressure myography...
December 14, 2018: American Journal of Physiology. Heart and Circulatory Physiology
K Kalavska, L Kucerova, S Schmidtova, L Toro, Z Kozovska, L Plank, M Chovanec, P Palacka, D Pindak, D Macak, J Mardiak, M Mego
Testicular germ cell tumors (TGCTs) are highly sensitive to cisplatin‑based chemotherapy. Nevertheless, there are metastatic tumors that do not completely respond to front‑line chemotherapy. For these tumors, surgical resection of residual masses is necessary to achieve long‑term disease control. Resected tissues represent valuable clinical material, which may be used for the engraftment into immunocompromised mice to produce patient‑derived xenografts (PDXs). They typically maintain similarities to the parental tumors and therefore serve as more realistic preclinical models...
October 5, 2018: Oncology Reports
Su Su, Anyonya R Guntur, Daniel C Nguyen, Shameem S Fakory, Chad C Doucette, Cassandra Leech, Humphrey Lotana, Matthew Kelley, Jaspreet Kohli, Julieta Martino, Sunder Sims-Lucas, Lucy Liaw, Calvin Vary, Clifford J Rosen, Aaron C Brown
Molecular- and cellular-based therapies have the potential to reduce obesity-associated disease. In response to cold, beige adipocytes form in subcutaneous white adipose tissue and convert energy stored in metabolic substrates to heat, making them an attractive therapeutic target. We developed a robust method to generate a renewable source of human beige adipocytes from induced pluripotent stem cells (iPSCs). Developmentally, these cells are derived from FOXF1+ mesoderm and progress through an expandable mural-like mesenchymal stem cell (MSC) to form mature beige adipocytes that display a thermogenically active profile...
December 11, 2018: Cell Reports
Wenli Yang, Patrick Seale
Beige fat cells hold significant promise for reducing obesity and metabolic disease. Su et al. (2018) present a robust method to produce human beige adipocytes from pluripotent stem cells via the generation of an expandable intermediary population of mesenchymal progenitor cells.
December 11, 2018: Cell Reports
Joseph Zhou, Anil Poudel, Prashanth Chandramani-Shivalingappa, Biao Xu, Ryan Welchko, Lixin Li
PURPOSE: Glucagon like peptide-1 (GLP-1) is produced to induce postprandial insulin secretion. Liraglutide, a full agonist of the GLP-1 receptor, has a protective effect on weight gain in obese subjects. Brown adipose tissue plays a major role in the control of energy balance and is known to be involved in the weight loss regulated by liraglutide. The putative anti-obesity properties of liraglutide and the cell signaling pathways involved were examined. METHODS: Four groups of C57/BL6 mice fed with chow or HFHS diet were injected with either liraglutide or vehicle for four weeks...
December 9, 2018: Endocrine
Aejin Lee, Ouliana Ziouzenkova
White adipose tissue (WAT) stores energy and also plays an important endocrine role in producing adipokines for communication with the peripheral and central nervous system. WAT consists of the major lipogenic unilocular adipocytes and the minor populations of beige and brite multilocular adipocytes. These multilocular adipocytes express thermogenic genes and have phenotypic similarity with thermogenic brown adipose tissue. According to a current paradigm, multilocular adipocytes have a thermogenic function in WAT...
February 2019: Neural Regeneration Research
Yang He, Rui-Xin Liu, Min-Ting Zhu, Wen-Bin Shen, Jing Xie, Zhi-Yin Zhang, Na Chen, Chang Shan, Xing-Zhi Guo, Yi-de Lu, Bei Tao, Li-Hao Sun, Hong-Yan Zhao, Rui Guo, Biao Li, Si-Min Liu, Guang Ning, Ji-Qiu Wang, Jian-Min Liu
BACKGROUND: Parathyroid hormone related protein (PTHrP) triggers white adipose tissue (WAT) browning and cachexia in lung cancer mouse models. It remains unknown whether excessive PTH secretion affects WAT browning and to what extent it contributes to body weight change in primary hyperparathyroidism (PHPT). METHODS: Using the adeno-associated virus injection, Pth gene over-expressed mice mimicking PHPT were firstly established to observe their WAT browning and body weight alteration...
December 6, 2018: EBioMedicine
Alma-Martina Cepika, Yohei Sato, Jeffrey Mao-Hwa Liu, Molly Javier Uyeda, Rosa Bacchetta, Maria Grazia Roncarolo
Monogenic diseases of the immune system, also known as inborn errors of immunity, are caused by single-gene mutations resulting in immune deficiency and dysregulation. More than 350 diseases have been described to date, and the number is rapidly expanding, with increasing availability of next-generation sequencing facilitating the diagnosis. The spectrum of immune dysregulation is wide, encompassing deficiencies in humoral, cellular, innate, and adaptive immunity; phagocytosis; and the complement system, which lead to autoinflammation and autoimmunity...
December 2018: Journal of Allergy and Clinical Immunology
Hongsuk Park, Anyuan He, Min Tan, Jordan M Johnson, John M Dean, Terri A Pietka, Yali Chen, Xiangyu Zhang, Fong-Fu Hsu, Babak Razani, Katsuhiko Funai, Irfan J Lodhi
Peroxisomes perform essential functions in lipid metabolism, including fatty acid oxidation and plasmalogen synthesis. Here, we describe a role for peroxisomal lipid metabolism in mitochondrial dynamics in brown and beige adipocytes. Adipose tissue peroxisomal biogenesis was induced in response to cold exposure through activation of the thermogenic co-regulator PRDM16. Adipose-specific knockout of the peroxisomal biogenesis factor Pex16 (Pex16-AKO) in mice impaired cold tolerance, decreased energy expenditure, and increased diet-induced obesity...
December 4, 2018: Journal of Clinical Investigation
Candida J Rebello, Frank L Greenway, Frank H Lau, Yuan Lin, Jacqueline M Stephens, William D Johnson, Ann A Coulter
OBJECTIVE: Naringenin, a citrus flavonoid, prevents diet-induced weight gain and improves glucose and lipid metabolism in rodents. There is evidence that naringenin activates brown fat and increases energy expenditure in mice, but little is known about its effects in humans. The goal of this study was to examine the effects of naringenin on energy expenditure in adipose tissue. METHODS: Human white adipocyte cultures (hADSC) and abdominal subcutaneous adipose tissue (pWAT) were treated with naringenin for 7 to 14 days...
December 2, 2018: Obesity
A Kaisanlahti, T Glumoff
Mammalian adipose tissue is traditionally categorized into white and brown relating to their function and morphology: while white serves as an energy storage, brown adipose tissue acts as the heat generator maintaining the core body temperature. The most recently identified type of fat, beige adipocyte tissue, resembles brown fat by morphology and function but is developmentally more related to white. The synthesis of beige fat, so-called browning of white fat, has developed into a topical issue in diabetes and metabolism research...
November 30, 2018: Journal of Physiology and Biochemistry
Edward T Chouchani, Lawrence Kazak, Bruce M Spiegelman
Brown and beige adipocytes can catabolize stored energy to generate heat, and this distinct capacity for thermogenesis could be leveraged as a therapy for metabolic diseases like obesity and type 2 diabetes. Thermogenic adipocytes drive heat production through close coordination of substrate supply with the mitochondrial oxidative machinery and effectors that control the rate of substrate oxidation. Together, this apparatus affords these adipocytes with tremendous capacity to drive thermogenesis. The best characterized thermogenic effector is uncoupling protein 1 (UCP1)...
November 20, 2018: Cell Metabolism
Yingkai Sun, Rui Wang, Shaoqian Zhao, Wen Li, Wen Liu, Lingyun Tang, Zhugang Wang, Weiqing Wang, Rui-Xin Liu, Guang Ning, Jiqiu Wang, Jie Hong
Browning of white adipose tissue has been proven to be a potential target to fight against obesity and its metabolic commodities, making the exploration of molecules involved in browning process important. Among those browning agents reported recently, FGF21 play as a quite promising candidate for treating obesity for its obvious enhancement of thermogenic capacity in adipocyte and significant improvement of metabolic disorders in both mice and human. However, whether other members of FGF family play roles in adipose thermogenesis and obese development is still an open question...
November 1, 2018: Journal of Molecular Endocrinology
Sanem Eren Akarcan, Neslihan Edeer Karaca, Guzide Aksu, Ayca Aykut, Deniz Yilmaz Karapinar, Funda Cetin, Yesim Aydinok, Elif Azarsiz, Eleonora Gambineri, Ozgur Cogulu, Ezgi Ulusoy Severcan, Hudaver Alper, Necil Kutukculer
Introduction: LPS-responsive beige-like anchor (LRBA) protein deficiency is a disease of immune dysregulation with autoimmunity affecting various systems. Case Presentation: Two male siblings with a novel LRBA mutation had different primary findings at admission: the younger sibling had chronic early-onset diarrhoea and the elder one had autoimmune haemolytic anaemia. During long-term follow-up for IPEX phenotype, both developed hypogammaglobulinaemia, enteropathy and lung involvement...
October 2018: JMM Case Reports
Vanessa Pellegrinelli, Vivian J Peirce, Laura Howard, Samuel Virtue, Dénes Türei, Martina Senzacqua, Andrea Frontini, Jeffrey W Dalley, Antony R Horton, Guillaume Bidault, Ilenia Severi, Andrew Whittle, Kamal Rahmouni, Julio Saez-Rodriguez, Saverio Cinti, Alun M Davies, Antonio Vidal-Puig
Activation of brown adipose tissue-mediated thermogenesis is a strategy for tackling obesity and promoting metabolic health. BMP8b is secreted by brown/beige adipocytes and enhances energy dissipation. Here we show that adipocyte-secreted BMP8b contributes to adrenergic-induced remodeling of the neuro-vascular network in adipose tissue (AT). Overexpression of bmp8b in AT enhances browning of the subcutaneous depot and maximal thermogenic capacity. Moreover, BMP8b-induced browning, increased sympathetic innervation and vascularization of AT were maintained at 28 °C, a condition of low adrenergic output...
November 26, 2018: Nature Communications
Thomas Mani, Pascal Blarer, Florian R Storck, Marco Pittroff, Theo Wernicke, Patricia Burkhardt-Holm
Microplastics are emerging pollutants in water bodies worldwide. The environmental entry areas must be studied to localise their sources and develop preventative and remedial solutions. Rivers are major contributors to the marine microplastics load. Here, we focus on a specific type of plastic microbead (diameter 286-954 μm, predominantly opaque, white-beige) that was repeatedly identified in substantial numbers between kilometres 677 and 944 of the Rhine River, one of Europe's main waterways. Specifically, we aimed (i) to confirm the reported abrupt increase in microbead concentrations between the cities of Leverkusen and Duisburg and (ii) to assess the concentration gradient of these particles along this stretch at higher resolution...
November 15, 2018: Environmental Pollution
Qi Wu, Si Sun, Zhiyu Li, Qian Yang, Bei Li, Shan Zhu, Lijun Wang, Juan Wu, Jingping Yuan, Changhua Yang, Juanjuan Li, Shengrong Sun
Emerging evidence supports the pivotal roles of cancer-associated cachexia in biological behaviour of breast cancer. However, the mediators and mechanisms that mediate cancer-induced cachexia remain unclear. Here, we show that breast cancer-derived exosomes alter adipocytes and muscle cells in terms of increased catabolism characterized by the release of metabolites. Likewise, tumour cells cocultivated with mature adipocytes or C2C12 exhibit an aggressive phenotype through inducing epithelial-mesenchymal transition...
November 24, 2018: Adipocyte
Li Yao, Yuhan Lai, Fei Xue, Lina Sun, Jialian Wang
A beige-pigmented, Gram-stain-negative, aerobic, non-motile, rod-shaped bacterium, named 24T , was isolated from sludge of a pesticide manufacturing factory in Nantong, Jiangsu Province, China. 16S rRNA gene sequence analysis revealed that strain 24T shared highest similarity with Parapusillimonas granuli Ch07T (98.20 %), followed by Candidimonas nitroreducens SC-089T (98.07 %) and Paracandidimonas soli IMT-305T (98.03 %). Phylogenetic trees showed that strain 24T formed a distinct clade with Paracandidimonas soli IMT-305T ...
November 22, 2018: International Journal of Systematic and Evolutionary Microbiology
Michael E Symonds, Grace Farhat, Peter Aldiss, Mark Pope, Helen Budge
There is increasing evidence that the global rise in temperature is contributing to the onset of diabetes, which could be mediated by a concomitant reduction in brown fat activity. Brown (and beige) fat are characterised as possessing a unique mitochondrial protein uncoupling protein (UCP)1 that when activated can rapidly generate large amounts of heat. Primary environmental stimuli of UCP1 include cold-exposure and diet, leading to increased activity of the sympathetic nervous system and large amounts of lipid and glucose being oxidised by brown fat...
November 21, 2018: Adipocyte
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