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https://www.readbyqxmd.com/read/29138472/functional-characterization-of-the-ucp1-associated-oxidative-phenotype-of-human-epicardial-adipose-tissue
#1
Kanta Chechi, Pierre Voisine, Patrick Mathieu, Mathieu Laplante, Sébastian Bonnet, Frédéric Picard, Philippe Joubert, Denis Richard
Brown fat presence and metabolic activity has been associated with lower body mass index, higher insulin sensitivity and better cardiometabolic profile in humans. We, and others, have previously reported the presence of Ucp1, a marker of brown adipocytes, in human epicardial adipose tissue (eAT). Characterization of the metabolic activity and associated physiological relevance of Ucp1 within eAT, however, is still awaited. Here, we validate the presence of Ucp1 within human eAT and its 'beige' nature. Using in-vitro analytical approaches, we further characterize its thermogenic potential and demonstrate that human eAT is capable of undergoing enhanced uncoupling respiration upon stimulation...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133512/exosomes-from-adipose-derived-stem-cells-attenuate-adipose-inflammation-and-obesity-through-polarizing-m2-macrophages-and-beiging-in-white-adipose-tissues
#2
Hui Zhao, Qianwen Shang, Zhenzhen Pan, Yang Bai, Zequn Li, Huiying Zhang, Qiu Zhang, Chun Guo, Lining Zhang, Qun Wang
Adipose-derived stem cells (ADSCs) play critical roles in controlling obesity-associated inflammation and metabolic disorders. Exosomes from ADSCs exert protective effects in several diseases, but their roles in obesity and related pathological conditions remain unclear. Here we showed that treatment of obese mice with ADSC-derived exosomes facilitated their metabolic homeostasis including improved insulin sensitivity (27.8% improvement), reduced obesity and alleviated hepatic steatosis. ADSC-derived exosomes drove M2 macrophage polarization, inflammation reduction and beiging in white adipose tissues (WAT) of diet-induced obese mice...
November 13, 2017: Diabetes
https://www.readbyqxmd.com/read/29132013/chimeric-antigen-receptor-modified-t-cells-redirected-to-epha2-for-the-immunotherapy-of-non-small-cell-lung-cancer
#3
Ning Li, Shaohui Liu, Mingjiao Sun, Wei Chen, Xiaogang Xu, Zhu Zeng, Yemin Tang, Yongquan Dong, Alex H Chang, Qiong Zhao
Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) is overexpressed in more than 90% of non-small cell lung cancer (NSCLC) but not significantly in normal lung tissue. It is therefore an important tumor antigen target for chimeric antigen receptors (CAR)-T-based therapy in NSCLC. Here, we developed a specific CAR targeted to EphA2, and the anti-tumor effects of this CAR were investigated. A second generation CAR with co-stimulatory receptor 4-1BB targeted to EphA2 was developed. The functionality of EphA2-specific T cells in vitro was tested with flow cytometry and real-time cell electronic sensing system assays...
November 10, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29131244/a-review-on-irisin-a-new-protagonist-that-mediates-muscle-adipose-bone-neuron-connectivity
#4
B Grygiel-Górniak, M Puszczewicz
Physical activity improves the quality of life and decreases the risk of several diseases (i.e. stroke, hypertension, myocardial infarction, obesity, and malignancies). Skeletal muscles are considered as an endocrine organ that produces myokines characterized by a paracrine or endocrine activity. Irisin is a circulating hormone-like myokine and is secreted as a product of fibronectin type III domain-containing protein 5 from skeletal muscle in response to exercise. This molecule regulates the energy metabolism and acts in adipose tissue, bones, and nervous system...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29119382/role-of-brown-adipose-tissue-in-metabolic-syndrome-aging-and-cancer-cachexia
#5
REVIEW
Meng Dong, Jun Lin, Wonchung Lim, Wanzhu Jin, Hyuek Jong Lee
Brown adipose tissue (BAT) plays a fundamental role in maintaining body temperature by producing heat. BAT that had been know to exist only in mammals and the human neonate has received great attention for the treatment of obesity and diabetes due to its important function in energy metabolism, ever since it is recently reported that human adults have functional BAT. In addition, beige adipocytes, brown adipocytes in white adipose tissue (WAT), have also been shown to take part in whole body metabolism. Multiple lines of evidence demonstrated that transplantation or activation of BAT or/and beige adipocytes reversed obesity and improved insulin sensitivity...
November 8, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/29111497/effects-of-growth-hormone-on-uncoupling-protein-1-in-white-adipose-tissues-in-obese-mice
#6
Misa Hayashi, Kumi Futawaka, Rie Koyama, Yue Fan, Midori Matsushita, Asuka Hirao, Yuki Fukuda, Ayako Nushida, Syoko Nezu, Tetsuya Tagami, Kenji Moriyama
OBJECTIVE: The transition of white adipocytes to beige cells (a phenomenon referred to as browning or beigeing) during obesity has been previously reported. Our study aimed to examine the mechanisms through which obesity induced by a high fat diet (HFD) affects uncoupling protein 1 (UCP1) expression via signal transduction and activator of transcription 5 (STAT5s). DESIGN: Seven-week-old male C57BL/6J mice were fed a normal or HFD for 11weeks. Body weight, white adipose tissue weight, and blood lipid and glucose levels were measured...
October 24, 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/29101383/physiological-and-genomic-insights-into-the-lifestyle-of-arsenite-oxidizing-herminiimonas-arsenitoxidans
#7
Hyeon-Woo Koh, Moonsuk Hur, Myung-Suk Kang, Youn-Bong Ku, Rohit Ghai, Soo-Je Park
Arsenic, a representative toxic metalloid, is responsible for serious global health problems. Most organisms possess arsenic resistance strategies to mitigate this toxicity. Here, we reported a microorganism, strain AS8, from heavy metal/metalloid-contaminated soil that is able to oxidize arsenite, and investigated its physiological and genomic traits. Its cells were rod-shaped and Gram-negative, and formed small beige-pigmented colonies. 16S rRNA-based phylogenetic analysis indicated that the strain belongs to the genus Herminiimonas and is closely related to Herminiimonas glaciei UMB49(T) (98...
November 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29100408/a-novel-fc-engineered-human-icam-1-cd54-antibody-with-potent-anti-myeloma-activity-developed-by-cellular-panning-of-phage-display-libraries
#8
Katja Klausz, Michael Cieker, Christian Kellner, Hans-Heinrich Oberg, Dieter Kabelitz, Thomas Valerius, Renate Burger, Martin Gramatzki, Matthias Peipp
To identify antibodies suitable for multiple myeloma (MM) immunotherapy, a cellular screening approach was developed using plasma cell lines JK-6L and INA-6 and human synthetic single-chain fragment variable (scFv) phage libraries. Isolated phage antibodies were screened for myeloma cell surface reactivity. Due to its binding characteristics, phage PIII-15 was selected to generate the scFv-Fc fusion protein TP15-Fc with an Fc domain optimized for FcγRIIIa binding. Various MM cell lines and patient-derived CD138-positive malignant plasma cells, but not granulocytes, B or T lymphocytes from healthy donors were recognized by TP15-Fc...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29077398/control-of-adipogenic-differentiation-in-mesenchymal-stem-cells-via-endogenous-gene-activation-using-crispr-cas9
#9
Yuichi Furuhata, Yuta Nihongaki, Moritoshi Sato, Keitaro Yoshimoto
Mesenchymal stem cells (MSCs) are of interest in regenerative medicine owing to their multilineage differentiation and self-renewal properties. Understanding the in vivo differentiation process is necessary for clinical applications including cell therapy and transplantation. This remains challenging owing to the lack of induction methods that imitate the natural programming process. Endogenous gene regulation of tissue-specific transcription factors is therefore desirable. In the present study, we demonstrated endogenous activation of adipogenic genes through the dCas9-based transcription system and achieved efficient induction of different types of adipocyte-like cells from MSCs...
November 7, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29064586/a-pivotal-role-of-ampk-signaling-in-medicarpin-mediated-formation-of-brown-and-beige-adipocytes-from-c3h10t1-2-mesenchymal-stem-cells
#10
Khan Mohammad Imran, Dahyeon Yoon, Yong-Sik Kim
Obesity poses a substantial threat of a worldwide epidemic and requires better understanding of adipose-tissue biology as well as necessitates research into the etiology and therapeutic interventions. In this study, Medicarpin (Med), a natural pterocarpan, was selected (by screening) as a small-molecule inducer of adipocyte differentiation among 854 candidates by using C3H10T1/2 mesenchymal stem cell; a cellular model of adipogenesis. Med induced the expression of brown-adipocyte commitment marker Bmp7 as well as the early regulators of brown fat fate Pparγ, Prdm16, and Pgc-1α during differentiation of C3H10T1/2 mesenchymal stem cells...
October 24, 2017: BioFactors
https://www.readbyqxmd.com/read/29045824/enhanced-doxorubicin-delivery-to-hepatocellular-carcinoma-cells-via-cd147-antibody-conjugated-immunoliposomes
#11
Jian Wang, Zhitao Wu, Guoyu Pan, Junsheng Ni, Fangyuan Xie, Beige Jiang, Lixin Wei, Jie Gao, Weiping Zhou
HAb18G/CD147, an important marker in the progression of hepatocellular carcinoma (HCC), is highly expressed on the surface of HCC cells. To increase the therapeutic efficacy of Doxil (PEGylated liposomal doxorubicin) against HCC, we constructed CD147-targeted doxorubicin-loaded immunoliposomes (Anti-CD147 ILs-DOX) by conjugating F(ab')2 of a CD147-specific monoclonal antibody to DSPE-PEG-MAL, and then inserted the antibody-conjugated polymer to Doxil. Anti-CD147 ILs-DOX delivered DOX to CD147-overexpressing HCC cells specifically and efficiently in vitro and in vivo, resulting in enhanced therapeutic effects than non-targeted controls...
October 15, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29040448/male-brown-fat-specific-double-knockout-of-igfir-ir-atrophy-mitochondrial-fission-failure-impaired-thermogenesis-and-obesity
#12
Vanesa Viana-Huete, Carlos Guillén, Gema García, Silvia Fernández, Ana García-Aguilar, C R Kahn, Manuel Benito
It is unknown how the lack of IR (insulin receptor)/ IGFIR (insulin like growth factor receptor) in a tissue-specific manner does affect brown fat development and mitochondrial integrity and function and its impact on the redistribution of the adipose organ and the metabolic status. To address this important issue, we have developed the IR/IGFIR double knockout in brown adipose tissue-specific manner (DKO). Lack of those receptors caused a severe brown fat atrophy, an enhanced beige cell clusters in inguinal fat, loss of mitochondrial mass, mitochondrial damage related to cristae disruption, and the loss of proteins involved in autophagosome formation, mitophagy, mitochondrial quality control and dynamics and thermogenesis...
October 10, 2017: Endocrinology
https://www.readbyqxmd.com/read/29033835/farnesol-has-an-anti-obesity-effect-in-high-fat-diet-induced-obese-mice-and-induces-the-development-of-beige-adipocytes-in-human-adipose-tissue-derived-mesenchymal-stem-cells
#13
Hye-Lin Kim, Yunu Jung, Jinbong Park, Dong-Hyun Youn, JongWook Kang, Seona Lim, Beom Su Lee, Mi-Young Jeong, Seong-Kyu Choe, Raekil Park, Kwang Seok Ahn, Jae-Young Um
Brown adipocytes dissipate energy as heat and hence have an important therapeutic capacity for obesity. Development of brown-like adipocytes (also called beige) is also another attractive target for obesity treatment. Here, we investigated the effect of farnesol, an isoprenoid, on adipogenesis in adipocytes and on the browning of white adipose tissue (WAT) as well as on the weight gain of high-fat diet (HFD)-induced obese mice. Farnesol inhibited adipogenesis and the related key regulators including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α through the up-regulation of AMP-activated protein kinase in 3T3-L1 murine adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29031730/bidirectional-manipulation-of-gene-expression-in-adipocytes-using-crispra-and-sirna
#14
Morten Lundh, Kaja Pluciñska, Marie S Isidor, Patricia S S Petersen, Brice Emanuelli
OBJECTIVE: Functional investigation of novel gene/protein targets associated with adipocyte differentiation or function heavily relies on efficient and accessible tools to manipulate gene expression in adipocytes in vitro. Recent advances in gene-editing technologies such as CRISPR-Cas9 have not only eased gene editing but also greatly facilitated modulation of gene expression without altering the genome. Here, we aimed to develop and validate a competent in vitro adipocyte model of controllable functionality as well as multiplexed gene manipulation in adipocytes, using the CRISPRa "SAM" system and siRNAs to simultaneously overexpress and silence selected genes in the same cell populations...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031720/brown-adipocytes-can-display-a-mammary-basal-myoepithelial-cell-phenotype-in%C3%A2-vivo
#15
Li Li, Baoguo Li, Min Li, Chaoqun Niu, Guanlin Wang, Ting Li, Elżbieta Król, Wanzhu Jin, John R Speakman
OBJECTIVE: Previous work has suggested that white adipocytes may also show a mammary luminal secretory cell phenotype during lactation. The capacity of brown and beige/brite adipocytes to display a mammary cell phenotype and the levels at which they demonstrate such phenotypes in vivo is currently unknown. METHODS: To investigate the putative adipocyte origin of mammary gland cells, we performed genetic lineage-labeling experiments in BAT and the mammary glands...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29021914/retinoic-acid-induces-white-adipose-tissue-browning-by-increasing-adipose-vascularity-and-inducing-beige-adipogenesis-of-pdgfr%C3%AE-adipose-progenitors
#16
Bo Wang, Xing Fu, Xingwei Liang, Jeanene M Deavila, Zhixiu Wang, Liang Zhao, Qiyu Tian, Junxing Zhao, Noe Alberto Gomez, Sophie C Trombetta, Mei-Jun Zhu, Min Du
Formation of beige adipocytes within white adipose tissue enhances energy expenditure, which is a promising strategy to reduce obesity and prevent metabolic symptoms. Vitamin A and its bioactive metabolite, retinoic acid (RA), have regulatory roles in lipid metabolism. Here we report that RA induces white adipose tissue browning via activating vascular endothelial growth factor (VEGF) signaling. RA triggered angiogenesis and elicited de novo generation of platelet-derived growth factor receptor α positive (PDGFRα(+)) adipose precursor cells via VEGFA/VEGFR2 signaling...
2017: Cell Discovery
https://www.readbyqxmd.com/read/29019320/distinct-cellular-and-molecular-mechanisms-for-%C3%AE-3-adrenergic-receptor-induced-beige-adipocyte-formation
#17
Yuwei Jiang, Daniel C Berry, Jonathan M Graff
Beige/brite adipocytes are induced within white adipose tissues (WAT) and, when activated, consume glucose and fatty acids to produce heat. Classically, two stimuli have been used to trigger a beiging response: cold temperatures and β3-adrenergic receptor (Adrb3) agonists. These two beiging triggers have been used interchangeably but whether these two stimuli may induce beiging differently at cellular and molecular levels remains unclear. Here, we found that cold-induced beige adipocyte formation requires Adrb1, not Adrb3, activation...
October 11, 2017: ELife
https://www.readbyqxmd.com/read/28988965/do-estrogens-enhance-activation-of-brown-and-beiging-of-adipose-tissues
#18
Aaron P Frank, Biff F Palmer, Deborah J Clegg
Obesity and its associated co-morbidities are worldwide public health concerns. Obesity is characterized by excessive adipose tissue accumulation; however, it is important to recognize that human and rodent adipose tissues are made up of several distinct adipose tissue sub-types. White adipose tissue (WAT) is considered the prototypical fat cell, due to its capacity and capability to store large amounts of lipid. In contrast, brown adipose tissue (BAT) oxidizes substrates to generate heat. BAT contains more mitochondria than WAT and express uncoupling protein-1 (UCP1), which mediates BAT thermogenesis...
October 5, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28983409/systems-biology-reveals-uncoupling-beyond-ucp1-in-human-white-fat-derived-beige-adipocytes
#19
Elin Nyman, Stefano Bartesaghi, Rebecka Melin Rydfalk, Sandra Eng, Charlotte Pollard, Peter Gennemark, Xiao-Rong Peng, Gunnar Cedersund
Pharmaceutical induction of metabolically active beige adipocytes in the normally energy storing white adipose tissue has potential to reduce obesity. Mitochondrial uncoupling in beige adipocytes, as in brown adipocytes, has been reported to occur via the uncoupling protein 1 (UCP1). However, several previous in vitro characterizations of human beige adipocytes have only measured UCP1 mRNA fold increase, and assumed a direct correlation with metabolic activity. Here, we provide an example of pharmaceutical induction of beige adipocytes, where increased mRNA levels of UCP1 are not translated into increased protein levels, and perform a thorough analysis of this example...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28978420/fasting-the-microbiota-to-improve-metabolism
#20
Joel T Haas, Bart Staels
While intermittent or periodic fasting provides a variety of favorable health benefits, the molecular mediators of these effects are poorly understood. In this issue of Cell Metabolism, Li and colleagues (2017) highlight the role of gut microbiota in mediating benefits of intermittent fasting through activation of adipose tissue beiging.
October 3, 2017: Cell Metabolism
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