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Brown adipocyte

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https://www.readbyqxmd.com/read/29241534/integrating-extracellular-flux-measurements-and-genome-scale-modeling-reveals-differences-between-brown-and-white-adipocytes
#1
Alfred K Ramirez, Matthew D Lynes, Farnaz Shamsi, Ruidan Xue, Yu-Hua Tseng, C Ronald Kahn, Simon Kasif, Jonathan M Dreyfuss
White adipocytes are specialized for energy storage, whereas brown adipocytes are specialized for energy expenditure. Explicating this difference can help identify therapeutic targets for obesity. A common tool to assess metabolic differences between such cells is the Seahorse Extracellular Flux (XF) Analyzer, which measures oxygen consumption and media acidification in the presence of different substrates and perturbagens. Here, we integrate the Analyzer's metabolic profile from human white and brown adipocytes with a genome-scale metabolic model to predict flux differences across the metabolic map...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29238745/dye-based-mito-thermometry-and-its-application-in-thermogenesis-of-brown-adipocytes
#2
Tao-Rong Xie, Chun-Feng Liu, Jian-Sheng Kang
Mitochondrion is the main intracellular site for thermogenesis and attractive energy expenditure targeting for obesity therapy. Here, we develop a method of mitochondrial thermometry based on Rhodamine B methyl ester, which equilibrates as a thermosensitive mixture of nonfluorescent and fluorescent resonance forms. Using this approach, we are able to demonstrate that the efficacy of norepinephrine-induced thermogenesis is low, and measure the maximum transient rate of temperature increase in brown adipocytes...
2017: Biophysics Reports
https://www.readbyqxmd.com/read/29237539/cdkn2a-deficiency-promotes-adipose-tissue-browning
#3
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/29236751/lysophosphatidic-acid-receptor-mrna-levels-in-heart-and-white-adipose-tissue-are-associated-with-obesity-in-mice-and-humans
#4
Amy Brown, Intekhab Hossain, Lester J Perez, Carine Nzirorera, Kathleen Tozer, Kenneth D'Souza, Purvi C Trivedi, Christie Aguiar, Alexandra M Yip, Jennifer Shea, Keith R Brunt, Jean-Francois Legare, Ansar Hassan, Thomas Pulinilkunnil, Petra C Kienesberger
BACKGROUND: Lysophosphatidic acid (LPA) receptor signaling has been implicated in cardiovascular and obesity-related metabolic disease. However, the distribution and regulation of LPA receptors in the myocardium and adipose tissue remain unclear. OBJECTIVES: This study aimed to characterize the mRNA expression of LPA receptors (LPA1-6) in the murine and human myocardium and adipose tissue, and its regulation in response to obesity. METHODS: LPA receptor mRNA levels were determined by qPCR in i) heart ventricles, isolated cardiomyocytes, and perigonadal adipose tissue from chow or high fat-high sucrose (HFHS)-fed male C57BL/6 mice, ii) 3T3-L1 adipocytes and HL-1 cardiomyocytes under conditions mimicking gluco/lipotoxicity, and iii) human atrial and subcutaneous adipose tissue from non-obese, pre-obese, and obese cardiac surgery patients...
2017: PloS One
https://www.readbyqxmd.com/read/29235464/syk-kinase-mediates-brown-fat-differentiation-and-activation
#5
Marko Knoll, Sally Winther, Anirudh Natarajan, Huan Yang, Mengxi Jiang, Prathapan Thiru, Aliakbar Shahsafaei, Tony E Chavarria, Dudley W Lamming, Lei Sun, Jacob B Hansen, Harvey F Lodish
Brown adipose tissue (BAT) metabolism influences glucose homeostasis and metabolic health in mice and humans. Sympathetic stimulation of β-adrenergic receptors in response to cold induces proliferation, differentiation, and UCP1 expression in pre-adipocytes and mature brown adipocytes. Here we show that spleen tyrosine kinase (SYK) is upregulated during brown adipocyte differentiation and activated by β-adrenergic stimulation. Deletion or inhibition of SYK, a kinase known for its essential roles in the immune system, blocks brown and white pre-adipocyte proliferation and differentiation in vitro, and results in diminished expression of Ucp1 and other genes regulating brown adipocyte function in response to β-adrenergic stimulation...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29233981/a-mir-327-fgf10-fgfr2-mediated-autocrine-signaling-mechanism-controls-white-fat-browning
#6
Carina Fischer, Takahiro Seki, Sharon Lim, Masaki Nakamura, Patrik Andersson, Yunlong Yang, Jennifer Honek, Yangang Wang, Yanyan Gao, Fang Chen, Nilesh J Samani, Jun Zhang, Masato Miyake, Seiichi Oyadomari, Akihiro Yasue, Xuri Li, Yun Zhang, Yizhi Liu, Yihai Cao
Understanding the molecular mechanisms regulating beige adipocyte formation may lead to the development of new therapies to combat obesity. Here, we report a miRNA-based autocrine regulatory pathway that controls differentiation of preadipocytes into beige adipocytes. We identify miR-327 as one of the most downregulated miRNAs targeting growth factors in the stromal-vascular fraction (SVF) under conditions that promote white adipose tissue (WAT) browning in mice. Gain- and loss-of-function experiments reveal that miR-327 targets FGF10 to prevent beige adipocyte differentiation...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29230933/biology-and-pathological-implications-of-brown-adipose-tissue-promises-and-caveats-for-the-control-of-obesity-and-its-associated-complications
#7
Pablo Tapia, Marta Fernández-Galilea, Fermín Robledo, Pablo Mardones, José E Galgani, Víctor A Cortés
The discovery of metabolically active brown adipose tissue (BAT) in adult humans has fuelled the research of diverse aspects of this previously neglected tissue. BAT is solely present in mammals and its clearest physiological role is non-shivering thermogenesis, owing to the capacity of brown adipocytes to dissipate metabolic energy as heat. Recently, a number of other possible functions have been proposed, including direct regulation of glucose and lipid homeostasis and the secretion of a number of factors with diverse regulatory actions...
December 11, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/29222583/correction-to-pioglitazone-reduces-cold-induced-brown-fat-glucose-uptake-despite-induction-of-browning-in-cultured-human-adipocytes-a-randomised-controlled-trial-in-humans
#8
Rebecca K C Loh, Melissa F Formosa, Nina Eikelis, David A Bertovic, Mitchell J Anderson, Shane A Barwood, Shane Nanayakkara, Neale D Cohen, Andre La Gerche, Anne T Reutens, Kenneth S Yap, Thomas W Barber, Gavin W Lambert, Martin H Cherk, Stephen J Duffy, Bronwyn A Kingwell, Andrew L Carey
The baseline insulin data given in Table 1 for the placebo group were incorrectly reported as 51 ± 10 pmol/l instead of 48 ± 10 pmol/l. This mistake also impacts on data reported in Table 4.
December 8, 2017: Diabetologia
https://www.readbyqxmd.com/read/29217172/nobiletin-induces-brown-adipocyte-like-phenotype-and-ameliorates-stress-in-3t3-l1-adipocytes
#9
Jameel Lone, Hilal Ahmad Parray, Jong Won Yun
Browning of white adipocytes (beiging) is an attractive therapeutic strategy against obesity and its associated metabolic complications. Nobiletin (NOB) is a polymethoxylated flavone present in Citrus fruits and has been reported to have anti-obesity effects. Here, we report that nobiletin exerts dual modulatory effects on adipocytes via induction of browning in 3T3-L1 white adipocytes and amelioration of stress in adipocytes. Nobiletin-induced beiging was investigated by determining expression levels of beige-specific genes and proteins by RT-PCR and immunoblot analysis, respectively...
December 4, 2017: Biochimie
https://www.readbyqxmd.com/read/29212073/age-induced-changes-in-white-brite-and-brown-adipose-depots-a-mini-review
#10
Markus Schosserer, Johannes Grillari, Christian Wolfrum, Marcel Scheideler
Aging is a time-related process of functional decline at organelle, cellular, tissue, and organismal level that ultimately limits life. Cellular senescence is a state of permanent growth arrest in response to stress and one of the major drivers of aging and age-related disorders. Senescent cells accumulate with age, and removal of these cells delays age-related disorders in different tissues and prolongs healthy lifespan. One of the most studied aging mechanisms is the accumulation of reactive oxygen species damage in cells, organs, and organisms over time...
December 7, 2017: Gerontology
https://www.readbyqxmd.com/read/29203476/ucp1-deficiency-increases-adipose-tissue-monounsaturated-fatty-acid-synthesis-and-trafficking-to-the-liver
#11
Laura M Bond, James M Ntambi
Uncoupling protein-1 (UCP1) facilitates thermogenesis in brown and beige adipocytes and can promote energy expenditure by decreasing mitochondrial respiratory efficiency. Defects in UCP1 and brown adipose tissue thermogenesis subject animals to chronic cold stress and elicit compensatory responses to generate heat. How UCP1 regulates white adipose tissue (WAT) lipid biology and tissue crosstalk is not completely understood. Here, we probe the effect of UCP1 deficiency on fatty acid metabolism in inguinal and epididymal WAT and investigate how these metabolic perturbations influence hepatic lipid homeostasis...
December 3, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29202451/akt3-inhibits-adipogenesis-and-protects-from-diet-induced-obesity-via-signaling-pathway
#12
Liang Ding, Lifang Zhang, Sudipta Biswas, Rebecca C Schugar, J Mark Brown, Tatiana Byzova, Eugene Podrez
Three Akt isoforms, encoded by 3 separate genes, are expressed in mammals. While the roles of Akt1 and Akt2 in metabolism are well established, it is not yet known whether Akt3 plays a role in metabolic diseases. We now report that Akt3 protects mice from high-fat diet-induced obesity by suppressing an alternative pathway of adipogenesis via with no lysine protein kinase-1 (WNK1) and serum/glucocorticoid-inducible kinase 1 (SGK1). We demonstrate that Akt3 specifically phosphorylates WNK1 at T58 and promotes its degradation via the ubiquitin-proteasome pathway...
November 16, 2017: JCI Insight
https://www.readbyqxmd.com/read/29198749/mitochondrial-fission-is-associated-with-ucp1-activity-in-human-brite-beige-adipocytes
#13
Didier F Pisani, Valentin Barquissau, Jean-Claude Chambard, Diane Beuzelin, Rayane A Ghandour, Maude Giroud, Aline Mairal, Sophie Pagnotta, Saverio Cinti, Dominique Langin, Ez-Zoubir Amri
OBJECTIVE: Thermogenic adipocytes (i.e. brown or brite/beige adipocytes) are able to burn large amounts of lipids and carbohydrates as a result of highly active mitochondria and enhanced uncoupled respiration, due to UCP1 activity. Although mitochondria are the key organelles for this thermogenic function, limited human data are available. METHODS/RESULTS: We characterized changes in the mitochondrial function of human brite adipocytes, using hMADS cells as a model of white- to brite-adipocyte conversion...
November 22, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29188818/no-evidence-of-white-adipocyte-browning-after-endurance-exercise-training-in-obese-men
#14
T Tsiloulis, A L Carey, J Bayliss, B Canny, R C R Meex, M J Watt
BACKGROUND/OBJECTIVES: The phenomenon of adipocyte 'beiging' involves the conversion of non-classic brown adipocytes to brown-like adipose tissue with thermogenic, fat-burning properties, and this phenomenon has been shown in rodents to slow the progression of obesity-associated metabolic diseases. Rodent studies consistently report adipocyte beiging after endurance exercise training, indicating that increased thermogenic capacity in these adipocytes may underpin the improved health benefits of exercise training...
November 30, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29187824/the-implication-of-pgc-1%C3%AE-on-fatty-acid-transport-across-plasma-and-mitochondrial-membranes-in-the-insulin-sensitive-tissues
#15
REVIEW
Elżbieta Supruniuk, Agnieszka Mikłosz, Adrian Chabowski
PGC-1α coactivator plays a decisive role in the maintenance of lipid balance via engagement in numerous metabolic processes (i.e., Krebs cycle, β-oxidation, oxidative phosphorylation and electron transport chain). It constitutes a link between fatty acids import and their complete oxidation or conversion into bioactive fractions through the coordination of both the expression and subcellular relocation of the proteins involved in fatty acid transmembrane movement. Studies on cell lines and/or animal models highlighted the existence of an upregulation of the total and mitochondrial FAT/CD36, FABPpm and FATPs content in skeletal muscle in response to PGC-1α stimulation...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29178600/genetic-markers-of-brown-adipose-tissue-identity-and-in-vitro-brown-adipose-tissue-activity-in-humans
#16
Emmani B M Nascimento, Lauren M Sparks, Adeline Divoux, Marike W van Gisbergen, Evie P M Broeders, Johanna A Jörgensen, Gert Schaart, Nicole D Bouvy, Wouter D van Marken Lichtenbelt, Patrick Schrauwen
OBJECTIVE: Human brown adipose tissue (BAT) activity decreases with age and obesity. In addition to uncoupling protein 1 (UCP1), several genetic markers of BAT in humans have been published. However, the link between human BAT activity and genetic markers has been inadequately explored. METHODS: White adipose tissue (WAT) and BAT biopsies were obtained from 16 patients undergoing deep neck surgery. In vitro differentiated adipocytes were used to measure norepinephrine-stimulated mitochondrial uncoupling as a measure of in vitro BAT activity...
November 27, 2017: Obesity
https://www.readbyqxmd.com/read/29176631/lack-of-adipocyte-fndc5-irisin-expression-and-secretion-reduces-thermogenesis-and-enhances-adipogenesis
#17
D Pérez-Sotelo, A Roca-Rivada, I Baamonde, J Baltar, A I Castro, E Domínguez, M Collado, F F Casanueva, M Pardo
Irisin is a browning-stimulating molecule secreted from the fibronectin type III domain containing 5 precursor (FNDC5) by muscle tissue upon exercise stimulation. Despite its beneficial role, there is an unmet and clamorous need to discern many essential aspects of this protein and its mechanism of action not only as a myokine but also as an adipokine. Here we contribute to address this topic by revealing the nature and role of FNDC5/irisin in adipose tissue. First, we show that FNDC5/irisin expression and secretion are induced by adipocyte differentiation and confirm its over-secretion by human obese visceral (VAT) and subcutaneous (SAT) adipose tissues...
November 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29175051/fatty-acid-oxidation-is-required-for-active-and-quiescent-brown-adipose-tissue-maintenance-and-thermogenic-programing
#18
Elsie Gonzalez-Hurtado, Jieun Lee, Joseph Choi, Michael J Wolfgang
OBJECTIVE: To determine the role of fatty acid oxidation on the cellular, molecular, and physiologic response of brown adipose tissue to disparate paradigms of chronic thermogenic stimulation. METHODS: Mice with an adipose-specific loss of Carnitine Palmitoyltransferase 2 (Cpt2A-/-), that lack mitochondrial long chain fatty acid β-oxidation, were subjected to environmental and pharmacologic interventions known to promote thermogenic programming in adipose tissue...
November 11, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29175050/vacuolar-protein-sorting-13c-is-a-novel-lipid-droplet-protein-that-inhibits-lipolysis-in-brown-adipocytes
#19
Vanesa D Ramseyer, Victoria A Kimler, James G Granneman
OBJECTIVE: Brown adipose tissue (BAT) thermogenesis depends on the mobilization and oxidation of fatty acids from intracellular lipid droplets (LD) within brown adipocytes (BAs); however, the identity and function of LD proteins that control BAT lipolysis remain incomplete. Proteomic analysis of mouse BAT subcellular fractions identified vacuolar protein sorting 13C (VPS13C) as a novel LD protein. The aim of this work was to investigate the role of VPS13C on BA LDs. METHODS: Biochemical fractionation and high resolution confocal and immuno-transmission electron microscopy (TEM) were used to determine the subcellular distribution of VPS13C in mouse BAT, white adipose tissue, and BA cell culture...
November 12, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29172481/fucoxanthin-and-its-metabolite-fucoxanthinol-do-not-induce-browning-in-human-adipocytes
#20
Candida J Rebello, Frank L Greenway, William Johnson, David Ribnicky, Alexander Poulev, Krisztian Stadler, Ann Coulter
Evidence from rodent studies suggests that the anti-obesity effects of fucoxanthin relate to the activation of brown fat and the conversion of white adipocytes to the brown phenotype as well as to downregulation of adipocyte differentiation. Further, obese females given a fucoxanthin supplement for 12 weeks displayed a reduction in body weight. In this study, fucoxanthinol the metabolite present in human plasma, stimulated lipolysis acutely in human adipocytes. However, there was no effect on oxygen consumption rate or the mRNA expression of UCP1, CPT-1β, and GLUT4, the genes largely associated with the browning of adipose tissue and consequential metabolic effects, when human adipocytes were treated with fucoxanthin or fucoxanthinol...
November 27, 2017: Journal of Agricultural and Food Chemistry
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