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https://www.readbyqxmd.com/read/29351550/differential-actions-of-ppar-%C3%AE-and-ppar-%C3%AE-%C3%AE-on-beige-adipocyte-formation-a-study-in-the-subcutaneous-white-adipose-tissue-of-obese-male-mice
#1
Tamiris Lima Rachid, Flavia Maria Silva-Veiga, Francielle Graus-Nunes, Isabele Bringhenti, Carlos Alberto Mandarim-de-Lacerda, Vanessa Souza-Mello
BACKGROUND AND AIMS: Obesity compromises adipocyte physiology. PPARs are essential to adipocyte plasticity, but its isolated role in the browning phenomenon is not clear. This study aimed to examine whether activation of PPAR-α or PPAR-β/δ could induce beige cell depots in the subcutaneous white adipose tissue of diet-induced obese mice. MATERIAL AND METHODS: Sixty animals were randomly assigned to receive a control diet (C, 10% lipids) or a high-fat diet (HF, 50% lipids) for ten weeks...
2018: PloS One
https://www.readbyqxmd.com/read/29322691/raspberry-supplementation-improves-insulin-signaling-and-promotes-brown-like-adipocyte-development-in-white-adipose-tissue-of-obese-mice
#2
Tong Xing, Yifei Kang, Xinglian Xu, Bo Wang, Min Du, Mei-Jun Zhu
SCOPE: Excessive lipid accumulation in white adipose tissue (WAT) leads to chronic inflammation and metabolic dysfunction. Raspberry (RB) contains high amount of polyphenolics and dietary fibers. The objective of the study is to evaluate effects of RB supplementation on WAT morphology, inflammation and insulin signaling in high fat diet (HFD)-induced obese mice, and further explore the underlying mechanisms. METHODS AND RESULTS: C57BL/6J mice were fed with a control diet or a HFD supplemented with 0 or 5% freeze dried RB for 12 weeks...
January 10, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29320703/three-dimensional-adipose-tissue-imaging-reveals-regional-variation-in-beige-fat-biogenesis-and-prdm16-dependent-sympathetic-neurite-density
#3
Jingyi Chi, Zhuhao Wu, Chan Hee J Choi, Lily Nguyen, Saba Tegegne, Sarah E Ackerman, Audrey Crane, François Marchildon, Marc Tessier-Lavigne, Paul Cohen
While the cell-intrinsic pathways governing beige adipocyte development and phenotype have been increasingly delineated, comparatively little is known about how beige adipocytes interact with other cell types in fat. Here, we introduce a whole-tissue clearing method for adipose that permits immunolabeling and three-dimensional profiling of structures including thermogenic adipocytes and sympathetic innervation. We found that tissue architecture and sympathetic innervation differ significantly between subcutaneous and visceral depots...
January 9, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29320702/repression-of-adipose-tissue-fibrosis-through-a-prdm16-gtf2ird1-complex-improves-systemic-glucose-homeostasis
#4
Yutaka Hasegawa, Kenji Ikeda, Yong Chen, Diana L Alba, Daniel Stifler, Kosaku Shinoda, Takashi Hosono, Pema Maretich, Yangyu Yang, Yasushi Ishigaki, Jingyi Chi, Paul Cohen, Suneil K Koliwad, Shingo Kajimura
Adipose tissue fibrosis is a hallmark of malfunction that is linked to insulin resistance and type 2 diabetes; however, what regulates this process remains unclear. Here we show that the PRDM16 transcriptional complex, a dominant activator of brown/beige adipocyte development, potently represses adipose tissue fibrosis in an uncoupling protein 1 (UCP1)-independent manner. By purifying the PRDM16 complex, we identified GTF2IRD1, a member of the TFII-I family of DNA-binding proteins, as a cold-inducible transcription factor that mediates the repressive action of the PRDM16 complex on fibrosis...
January 9, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29317208/zinc-alpha2-glycoprotein-promotes-browning-in-adipocytes
#5
Xin-Hua Xiao, Xiao-Yan Qi, Ya-Di Wang, Li Ran, Jing Yang, Huan-Li Zhang, Can-Xin Xu, Ge-Bo Wen, Jiang-Hua Liu
Recent studies have highlighted recruiting and activating brite adipocytes in WAT (so-called "browning") would be an attractive anti-obesity strategy. Zinc alpha2 glycoprotein (ZAG) is reported to ameliorate glycolipid metabolism and lose body weight in obese mice. However whether the body reducing effect mediated by browning programme remains unclear. Here, we show that overexpression of ZAG in 3T3-L1 adipocytes enhanced expression of brown fat-specific markers (UCP-1, PRDM16 and CIDEA), mitochondrial biogenesis genes (PGC-1α, NRF-1/2 and mtTFA) and the key lipid metabolism lipases (ATGL, HSL, CPT1-A and p-acyl-CoA carboxylase)...
January 6, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29310926/identification-of-non-hla-genes-associated-with-development-of-islet-autoimmunity-and-type-1-diabetes-in-the-prospective-teddy-cohort
#6
Ashok Sharma, Xiang Liu, David Hadley, William Hagopian, Wei-Min Chen, Suna Onengut-Gumuscu, Carina Törn, Andrea K Steck, Brigitte I Frohnert, Marian Rewers, Anette-G Ziegler, Åke Lernmark, Jorma Toppari, Jeffrey P Krischer, Beena Akolkar, Stephen S Rich, Jin-Xiong She
Traditional linkage analysis and genome-wide association studies have identified HLA and a number of non-HLA genes as genetic factors for islet autoimmunity (IA) and type 1 diabetes (T1D). However, the relative risk associated with previously identified non-HLA genes is usually very small as measured in cases/controls from mixed populations. Genetic associations for IA and T1D may be more accurately assessed in prospective cohorts. In this study, 5806 subjects from the TEDDY (The Environmental Determinants of Diabetes in the Young) study, an international prospective cohort study, were genotyped for 176,586 SNPs on the ImmunoChip...
January 5, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29237539/cdkn2a-deficiency-promotes-adipose-tissue-browning
#7
Nabil Rabhi, Sarah Anissa Hannou, Xavier Gromada, Elisabet Salas, Xi Yao, Frédérik Oger, Charlène Carney, Isabel C Lopez-Mejia, Emmanuelle Durand, Iandry Rabearivelo, Amélie Bonnefond, Emilie Caron, Lluis Fajas, Christian Dani, Philippe Froguel, Jean-Sébastien Annicotte
OBJECTIVES: Genome-wide association studies have reported that DNA polymorphisms at the CDKN2A locus modulate fasting glucose in human and contribute to type 2 diabetes (T2D) risk. Yet the causal relationship between this gene and defective energy homeostasis remains elusive. Here we sought to understand the contribution of Cdkn2a to metabolic homeostasis. METHODS: We first analyzed glucose and energy homeostasis from Cdkn2a-deficient mice subjected to normal or high fat diets...
December 1, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29143709/acute-and-chronic-cold-exposure-differentially-affects-the-browning-of-porcine-white-adipose-tissue
#8
Y Gao, N R Qimuge, J Qin, R Cai, X Li, G Y Chu, W J Pang, G S Yang
Piglets are characteristically cold intolerant and thus susceptible to high mortality. However, browning of white adipose tissue (WAT) can induce non-shivering thermogenesis as a potential strategy to facilitate the animal's response to cold. Whether cold exposure can induce browning of subcutaneous WAT (sWAT) in piglets in a similar manner as it can in humans remains largely unknown. In this study, piglets were exposed to acute cold (4°C, 10 h) or chronic cold exposure (8°C, 15 days), and the genes and proteins of uncoupling protein 1 (UCP1)-dependent and independent thermogenesis, mitochondrial biogenesis, lipogenic and lipolytic processes were analysed...
November 16, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/29129783/hypoxia-induced-mir-214-expression-promotes-tumour-cell-proliferation-and-migration-by-enhancing-the-warburg-effect-in-gastric-carcinoma-cells
#9
Liuqing Yang, Weijie Zhang, Yanbo Wang, Tianhui Zou, Bin Zhang, Yuanyuan Xu, Taohong Pang, Qingqing Hu, Min Chen, Lei Wang, Ying Lv, Kai Yin, Hongwei Liang, Xi Chen, Guifang Xu, Xiaoping Zou
miR-214 is an important oncomiRNA and is upregulated in various types of cancer, including gastric cancer. However, the molecular mechanism underlying the ectopic expression and function of miR-214 in gastric cancer is largely undefined. In this study, we found that miR-214 induces the Warburg effect and promotes the migration and proliferation of human gastric cancer cells. According to the mechanistic analysis, miR-214 expression is induced by environmental hypoxia, and miR-214 mediates hypoxia-induced functions...
November 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29105287/gut-microbiota-interacts-with-markers-of-adipose-tissue-browning-insulin-action-and-plasma-acetate-in-morbid-obesity
#10
José María Moreno-Navarrete, Matteo Serino, Vincent Blasco-Baque, Vincent Azalbert, Richard H Barton, Marina Cardellini, Jèssica Latorre, Francisco Ortega, Mònica Sabater-Masdeu, Rémy Burcelin, Marc-Emmanuel Dumas, Wifredo Ricart, Massimo Federici, José Manuel Fernández-Real
SCOPE: To examine the potential relationship among gene expression markers of adipose tissue browning, gut microbiota and insulin sensitivity in humans. METHODS AND RESULTS: Gut microbiota composition and gene markers of browning were analysed in subcutaneous (SAT) and visceral (VAT) adipose tissue from morbidly obese subjects (n = 34). Plasma acetate was measured through (1) H NMR and insulin sensitivity using euglycemic hyperinsulinemic clamp. Subjects with insulin resistance showed an increase in the relative abundance (RA) of the phyla Bacteroidetes and Proteobacteria while RA of Firmicutes was decreased...
November 3, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29081505/serotonin-prevents-differentiation-into-brown-adipocytes-and-induces-trans-differentiation-into-white-adipocytes
#11
S Rozenblit-Susan, N Chapnik, O Froy
BACKGROUND/OBJECTIVES: Serotonin is synthesized by many cells in the periphery to affect vasoconstriction, intestinal motility, and glucose and lipid metabolism. It has recently been shown that serotonin leads to fat accumulation in white adipose tissue (WAT). However, the direct effect of serotonin on adipose tissue (BAT) differentiation and metabolism is limited. Therefore, our aim was to investigate the effect of serotonin on brown adipocyte metabolism and differentiation. METHODS: Non-differentiated HIB1B cells and differentiated HIB1B brown adipocytes were treated with serotonin and their metabolism and differentiation examined...
October 30, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29066463/angiotensin-1-7-stimulates-brown-adipose-tissue-and-reduces-diet-induced-obesity
#12
Hidechika Morimoto, Jun Mori, Hisakazu Nakajima, Yasuhiro Kawabe, Yusuke Tsuma, Shota Fukuhara, Kazuki Kodo, Kazuya Ikoma, Satoaki Matoba, Gavin Y Oudit, Hajime Hosoi
The renin-angiotensin system is a key regulator of metabolism with beneficial effects of the angiotensin 1-7 peptide. We hypothesized that the anti-obesity effect of Ang 1-7 is related to the stimulation of brown adipose tissue (BAT). We administered Ang 1-7 (0.54 mg・kg-1・d-1) for 28 days via implanted micro-osmotic pumps to mice with high-fat diet (HFD) induced obesity. Ang 1-7 treatment reduced body weight, upregulated thermogenesis and ameliorated impaired glucose homeostasis without affecting food consumption...
October 24, 2017: American Journal of Physiology. Endocrinology and Metabolism
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
#13
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/29063609/integrated-genome-analysis-of-uterine-leiomyosarcoma-to-identify-novel-driver-genes-and-targetable-pathways
#14
Tine Cuppens, Matthieu Moisse, Jeroen Depreeuw, Daniela Annibali, Eva Colas, Antonio Gil-Moreno, Jutta Huvila, Olli Carpén, Michal Zikán, Xavier Matias-Guiu, Philippe Moerman, Sabrina Croce, Diether Lambrechts, Frédéric Amant
Uterine leiomyosarcomas (uLMS) are rare, aggressive malignancies for which limited treatment options are available. To gain novel molecular insights into uLMS and identify potential novel therapeutic targets, we characterized 84 uLMS samples for genome-wide somatic copy number alterations, mutations, gene fusions and gene expression, and performed a data integration analysis. We found that alterations affecting TP53, RB1, PTEN, MED12, YWHAE and VIPR2 were present in the majority of uLMS. Pathway analyses additionally revealed that the PI3K/AKT/mTOR, estrogen-mediated S-phase entry and DNA damage response signaling pathways, for which inhibitors have already been developed and approved, frequently harbored genetic changes...
October 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29053761/the-transcription-factor-prdm16-marks-a-single-retinal-ganglion-cell-subtype-in-the-mouse-retina
#15
Sergio Groman-Lupa, Joseph Adewumi, Ko Uoon Park, Joseph A Brzezinski Iv
Purpose: Retinal ganglion cells (RGC) can be categorized into roughly 30 distinct subtypes. How these subtypes develop is poorly understood, in part because few unique subtype markers have been characterized. We tested whether the Prdm16 transcription factor is expressed by RGCs as a class or within particular ganglion cell subtypes. Methods: Embryonic and mature retinal sections and flatmount preparations were examined by immunohistochemistry for Prdm16 and several other cell type-specific markers...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29031730/bidirectional-manipulation-of-gene-expression-in-adipocytes-using-crispra-and-sirna
#16
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/29021914/retinoic-acid-induces-white-adipose-tissue-browning-by-increasing-adipose-vascularity-and-inducing-beige-adipogenesis-of-pdgfr%C3%AE-adipose-progenitors
#17
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
#18
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/28988768/crosstalk-between-kcnk3-mediated-ion-current-and-adrenergic-signaling-regulates-adipose-thermogenesis-and-obesity
#19
Yi Chen, Xing Zeng, Xuan Huang, Sara Serag, Clifford J Woolf, Bruce M Spiegelman
Adrenergic stimulation promotes lipid mobilization and oxidation in brown and beige adipocytes, where the harnessed energy is dissipated as heat in a process known as adaptive thermogenesis. The signaling cascades and energy-dissipating pathways that facilitate thermogenesis have been extensively described, yet little is known about the counterbalancing negative regulatory mechanisms. Here, we identify a two-pore-domain potassium channel, KCNK3, as a built-in rheostat negatively regulating thermogenesis. Kcnk3 is transcriptionally wired into the thermogenic program by PRDM16, a master regulator of thermogenesis...
November 2, 2017: Cell
https://www.readbyqxmd.com/read/28934139/phyllodulcin-a-natural-sweetener-regulates-obesity-related-metabolic-changes-and-fat-browning-related-genes-of-subcutaneous-white-adipose-tissue-in-high-fat-diet-induced-obese-mice
#20
Eunju Kim, Soo-Min Lim, Min-Soo Kim, Sang-Ho Yoo, Yuri Kim
Phyllodulcin is a natural sweetener found in Hydrangea macrophylla var. thunbergii. This study investigated whether phyllodulcin could improve metabolic abnormalities in high-fat diet (HFD)-induced obese mice. Animals were fed a 60% HFD for 6 weeks to induce obesity, followed by 7 weeks of supplementation with phyllodulcin (20 or 40 mg/kg body weight (b.w.)/day). Stevioside (40 mg/kg b.w./day) was used as a positive control. Phyllodulcin supplementation reduced subcutaneous fat mass, levels of plasma lipids, triglycerides, total cholesterol, and low-density lipoprotein cholesterol and improved the levels of leptin, adiponectin, and fasting blood glucose...
September 21, 2017: Nutrients
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