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https://www.readbyqxmd.com/read/28530121/glucocorticoids-retain-bi-potent-fibroblast-progenitors-during-alveolar-septation-in-mice
#1
Stephen E McGowan, Diann M McCoy
Glucocorticoids have been widely used and exert pleiotropic effects on alveolar structure and function, but do not improve the long-term clinical outcomes for patients with bronchopulmonary dysplasia, emphysema, or interstitial lung diseases. Treatments which foster alveolar regeneration could substantially improve the long-term outcomes for such patients. One approach to alveolar regeneration is to stimulate and guide intrinsic alveolar progenitors along developmental pathways used during secondary septation...
May 21, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28493443/natural-alkaloid-bouchardatine-ameliorates-metabolic-disorders-in-high-fat-diet-fed-mice-via-stimulating-the-sirt1-lkb1-ampk-axis
#2
Yong Rao, Hong Yu, Lin Gao, Yu-Ting Lu, Zhao Xu, Hong Liu, Lian-Quan Gu, Ji-Ming Ye, Zhi-Shu Huang
BACKGROUND AND PURPOSE: Promoting energy metabolism is known to provide therapeutic effects for obesity and associated metabolic disorders. The present study evaluated the therapeutic effects of the newly-identified bouchardatine (Bou) on obesity associated metabolic disorders and the molechular mechanisms for these effects. EXPERIMENTAL APPROACH: The molecular mode of action of Bou for its effects on lipid metabolism was first examined in 3T3-L1 adipocytes and HepG2 cells...
May 10, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28486585/cold-adaptation-in-pigs-depends-on-ucp3-in-beige-adipocytes
#3
Jun Lin, Chunwei Cao, Cong Tao, Rongcai Ye, Meng Dong, Qiantao Zheng, Chao Wang, Xiaoxiao Jiang, Guosong Qin, Changguo Yan, Kui Li, John R Speakman, Yanfang Wang, Wanzhu Jin, Jianguo Zhao
Pigs lack functional UCP1 making them susceptible to cold. Nevertheless, several pig breeds are known to be cold resistant. The molecular mechanism(s) enabling such adaptation are currently unknown. Here, we show that this resistance is not dependent on shivering, but rather depends on UCP3 and white adipose tissue (WAT) browning. In two cold-resistant breeds (Tibetan and Min), but not a cold-sensitive breed (Bama), WAT browning was induced after cold exposure. Beige adipocytes from Tibetan pigs exhibited greater oxidative capacity than those from Bama pigs...
May 9, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28484396/nesfatin-1-in-the-lateral-parabrachial-nucleus-inhibits-food-intake-modulates-excitability-of-glucosensing-neurons-and-enhances-ucp1-expression-in-brown-adipose-tissue
#4
Jun-Hua Yuan, Xi Chen, Jing Dong, Di Zhang, Kun Song, Yue Zhang, Guang-Bo Wu, Xi-Hao Hu, Zheng-Yao Jiang, Peng Chen
Nesfatin-1, an 82-amino acid neuropeptide, has been shown to induce anorexia and energy expenditure. Food intake is decreased in ad libitum-fed rats following injections of nesfatin-1 into the lateral, third, or fourth ventricles of the brain. Although the lateral parabrachial nucleus (LPBN) is a key regulator of feeding behavior and thermogenesis, the role of nesfatin-1 in this structure has not yet been delineated. We found that intra-LPBN microinjections of nesfatin-1 significantly reduced nocturnal cumulative food intake and average meal sizes without affecting meal numbers in rats...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28481291/inflammation-downregulates-ucp1-expression-in-brown-adipocytes-potentially-via-sirt1-and-dbc1-interaction
#5
Mark K Nøhr, Natalia Bobba, Bjørn Richelsen, Sten Lund, Steen B Pedersen
Brown adipose tissue thermogenesis at the cost of energy is not only important for the development of obesity, but also possesses great promise in anti-obesity treatment. Uncoupling protein 1 (UCP1) expression has been reported to be under control of the intracellular deacetylase SIRT1. Here, we investigated the effect and mechanism of inflammation and sirtuin-1 (SIRT1) activation on the induction of thermogenic genes in immortalized brown adipocytes incubated with LPS or IL1β and mice with elevated inflammatory tone...
May 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28481288/an-additive-effect-of-promoting-thermogenic-gene-expression-in-mice-adipose-derived-stromal-vascular-cells-by-combination-of-rosiglitazone-and-cl316-243
#6
You-Lei Li, Xiao Li, Tian-Tuan Jiang, Jia-Min Fan, Xue-Li Zheng, Xin-E Shi, Tai-Yong Yu, Gui-Yan Chu, Gong-She Yang
It is well-documented that CL316,243 (a β3 agonist) or rosiglitazone (a PPARγ agonist) can induce white adipocyte populations to brown-like adipocytes, thus increasing energy consumption and combating obesity. However, whether there is a combined effect remains unknown. In the present study, stromal vascular cells of inguinal white adipose tissue (iWAT-SVCs for short) from mice were cultured and induced into browning by CL316,243, rosiglitazone, or both. Results showed that a combination of CL316,243 and rosiglitazone significantly upregulated the expression of the core thermogenic gene Ucp1 as well as genes related with mitochondrial function (Cidea, Cox5b, Cox7a1, Cox8b, and Cycs), compared with the treatment of CL316,243 or rosiglitazone alone...
May 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28469599/the-role-of-thyrotropin-receptor-activation-in-adipogenesis-and-modulation-of-fat-phenotype
#7
Mohd Shazli Draman, Michael Stechman, David Scott-Coombes, Colin M Dayan, Dafydd Aled Rees, Marian Ludgate, Lei Zhang
Evidence from clinical and experimental data suggests that thyrotropin receptor (TSHR) signaling is involved in energy expenditure through its impact on white adipose tissue (WAT) and brown adipose tissue (BAT). TSHR expression increases during mesenchymal stem cell (MSC) differentiation into fat. We hypothesize that TSHR activation [TSHR*, elevated thyroid-stimulating hormone, thyroid-stimulating antibodies (TSAB), or activating mutation] influences MSC differentiation, which contributes to body composition changes seen in hypothyroidism or Graves' disease (GD)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28467890/brown-and-brite-adipocytes-same-function-but-different-origin-and-response
#8
REVIEW
Dinh-Toi Chu, Barbara Gawronska-Kozak
Inducing brown adipocytes in white adipose tissues is a promising target to combat obesity and its related disorders in human beings. This goal has been especially encouraged by new important discoveries of human brown adipose tissues. The accumulating evidence confirms the presence of active brown adipocytes, not only in newborns, but also in adult humans. In rodents, there are two populations of the Ucp1-expressing adipocytes with well characterized-thermogenic functions, classical interscapular brown adipocytes and brite/beige adipocytes (brown adipocytes that are induced in white adipose tissues)...
April 30, 2017: Biochimie
https://www.readbyqxmd.com/read/28455142/a-fish-oil-diet-induces-mitochondrial-uncoupling-and-mitochondrial-unfolded-protein-response-in-epididymal-white-adipose-tissue-of-mice
#9
Shylesh Bhaskaran, Archana Unnikrishnan, Rojina Ranjit, Rizwan Qaisar, Gavin Pharaoh, Stephanie Matyi, Michael Kinter, Sathyaseelan S Deepa
White adipose tissue (WAT) mitochondrial dysfunction is linked to the pathogenesis of obesity driven insulin resistance. Dietary conditions that alter fat mass are known to affect white adipocyte mitochondrial function, however, the impact of high calorie diets on white adipocyte mitochondria is not fully understood. The aim of this study is to assess the effect of a diet rich in saturated or polyunsaturated fat on mitochondrial unfolded protein response (UPR(mt)), a retrograde signaling response that maintains mitochondrial homeostasis, in epididymal WAT (eWAT)...
April 26, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28453364/quantification-of-ucp1-function-in-human-brown-adipose-tissue
#10
Craig Porter
Brown adipose tissue (BAT) mitochondria are distinct from their counterparts in other tissues in that ATP production is not their primary physiologic role. BAT mitochondria are equipped with a specialized protein known as uncoupling protein 1 (UCP1). UCP1 short-circuits the electron transport chain, allowing mitochondrial membrane potential to be transduced to heat, making BAT a tissue capable of altering energy expenditure and fuel metabolism in mammals without increasing physical activity. The recent discovery that adult humans have metabolically active BAT has rekindled an interest in this intriguing tissue, with the overarching aim of manipulating BAT function to augment energy expenditure as a countermeasure for obesity and the metabolic abnormalities it incurs...
April 14, 2017: Adipocyte
https://www.readbyqxmd.com/read/28452586/stress-turns-on-the-heat-regulation-of-mitochondrial-biogenesis-and-ucp1-by-ros-in-adipocytes
#11
Sara P Ortega, Edward T Chouchani, Sihem Boudina
Reactive oxygen species (ROS) production and oxidative stress (OS) in adipose tissue are associated with obesity and insulin resistance (IR). The nature of this relationship i.e., cause and effect or consequence has not been clearly determined. We provide evidence that elevated mitochondrial ROS generated by adipocytes from mice with diet-induced obesity (DIO) represents an adaptive mechanism that precipitates fatty acid oxidation, mitochondrial biogenesis, and mitochondrial uncoupling in an effort to defend against weight gain...
January 2, 2017: Adipocyte
https://www.readbyqxmd.com/read/28442343/pig-has-no-uncoupling-protein-1
#12
Lianjie Hou, Jia Shi, Lingbo Cao, Guli Xu, Chingyuan Hu, Chong Wang
Brown adipose tissue (BAT) is critical for mammal's survival in the cold environment. Uncoupling protein 1 (UCP1) is responsible for the non-shivering thermogenesis in the BAT. Pig is important economically as a meat-producing livestock. However, whether BAT or more precisely UCP1 protein exists in pig remains a controversy. The objective of this study was to ascertain whether pig has UCP1 protein. In this study, we used rapid amplification of cDNA ends (RACE) technique to obtain the UCP1 mRNA 3' end sequence, confirmed only exons 1 and 2 of the UCP1 gene are transcribed in the pig...
June 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28436955/vitamin-a-mediates-conversion-of-monocyte-derived-macrophages-into-tissue-resident-macrophages-during-alternative-activation
#13
Uma Mahesh Gundra, Natasha M Girgis, Michael A Gonzalez, Mei San Tang, Hendrik J P Van Der Zande, Jian-Da Lin, Mireille Ouimet, Lily J Ma, Jordan Poles, Nikollaq Vozhilla, Edward A Fisher, Kathryn J Moore, P'ng Loke
It remains unclear whether activated inflammatory macrophages can adopt features of tissue-resident macrophages, or what mechanisms might mediate such a phenotypic conversion. Here we show that vitamin A is required for the phenotypic conversion of interleukin 4 (IL-4)-activated monocyte-derived F4/80(int)CD206(+)PD-L2(+)MHCII(+) macrophages into macrophages with a tissue-resident F4/80(hi)CD206(-)PD-L2(-)MHCII(-)UCP1(+) phenotype in the peritoneal cavity of mice and during the formation of liver granulomas in mice infected with Schistosoma mansoni...
April 24, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28431116/ontogeny-and-thermogenic-role-for-sternal-fat-in-female-sheep
#14
Belinda A Henry, Mark Pope, Mark Birtwistle, Rachael Loughnan, Reham Alagal, John-Paul Fuller-Jackson, Viv Perry, Helen Budge, Iain J Clarke, Michael E Symonds
Brown adipose tissue acting through a unique uncoupling protein (UCP1) has a critical role in preventing hypothermia in new-born sheep but is then considered to rapidly disappear during postnatal life. The extent to which the anatomical location of fat influences postnatal development and thermogenic function, particularly following feeding, in adulthood, are not known and were both examined in our study. Changes in gene expression of functionally important pathways (i.e. thermogenesis, development, adipogenesis and metabolism) were compared between sternal and retroperitoneal fat depots together with a representative skeletal muscle over the first month of postnatal life, coincident with the loss of brown fat and accumulation of white fat...
April 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28414329/alternatively-activated-macrophages-do-not-synthesize-catecholamines-or-contribute-to-adipose-tissue-adaptive-thermogenesis
#15
Katrin Fischer, Henry H Ruiz, Kevin Jhun, Brian Finan, Douglas J Oberlin, Verena van der Heide, Anastasia V Kalinovich, Natasa Petrovic, Yochai Wolf, Christoffer Clemmensen, Andrew C Shin, Senad Divanovic, Frank Brombacher, Elke Glasmacher, Susanne Keipert, Martin Jastroch, Joachim Nagler, Karl-Werner Schramm, Dasa Medrikova, Gustav Collden, Stephen C Woods, Stephan Herzig, Dirk Homann, Steffen Jung, Jan Nedergaard, Barbara Cannon, Matthias H Tschöp, Timo D Müller, Christoph Buettner
Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through β3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process...
May 2017: Nature Medicine
https://www.readbyqxmd.com/read/28414311/a-self-sustained-loop-of-inflammation-driven-inhibition-of-beige-adipogenesis-in-obesity
#16
Kyoung-Jin Chung, Antonios Chatzigeorgiou, Matina Economopoulou, Ruben Garcia-Martin, Vasileia I Alexaki, Ioannis Mitroulis, Marina Nati, Janine Gebler, Tjalf Ziemssen, Susan E Goelz, Julia Phieler, Jong-Hyung Lim, Katia P Karalis, Thalia Papayannopoulou, Matthias Blüher, George Hajishengallis, Triantafyllos Chavakis
In obesity, inflammation of white adipose tissue (AT) is associated with diminished generation of beige adipocytes ('beige adipogenesis'), a thermogenic and energy-dissipating function mediated by beige adipocytes that express the uncoupling protein UCP1. Here we delineated an inflammation-driven inhibitory mechanism of beige adipogenesis in obesity that required direct adhesive interactions between macrophages and adipocytes mediated by the integrin α4 and its counter-receptor VCAM-1, respectively; expression of the latter was upregulated in obesity...
June 2017: Nature Immunology
https://www.readbyqxmd.com/read/28414270/human-biallelic-mfn2-mutations-induce-mitochondrial-dysfunction-upper-body-adipose-hyperplasia-and-suppression-of-leptin-expression
#17
Nuno Rocha, David A Bulger, Andrea Frontini, Hannah Titheradge, Sigrid Bjerge Gribsholt, Rachel Knox, Matthew Page, Julie Harris, Felicity Payne, Claire Adams, Alison Sleigh, John Crawford, Anette Prior Gjesing, Jette Bork-Jensen, Oluf Pedersen, Inês Barroso, Torben Hansen, Helen Cox, Mary Reilly, Alex Rossor, Rebecca J Brown, Simeon I Taylor, Duncan McHale, Martin Armstrong, Elif A Oral, Vladimir Saudek, Stephen O'Rahilly, Eamonn R Maher, Bjørn Richelsen, David B Savage, Robert K Semple
MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial network fragmentation, disorganised cristae, and increased autophagosomes...
April 19, 2017: ELife
https://www.readbyqxmd.com/read/28408438/prdm16-represses-the-type-i-interferon-response-in-adipocytes-to-promote-mitochondrial-and-thermogenic-programing
#18
Megan Kissig, Jeff Ishibashi, Matthew J Harms, Hee-Woong Lim, Rachel R Stine, Kyoung-Jae Won, Patrick Seale
Brown adipose has the potential to counteract obesity, and thus, identifying signaling pathways that regulate the activity of this tissue is of great clinical interest. PRDM16 is a transcription factor that activates brown fat-specific genes while repressing white fat and muscle-specific genes in adipocytes. Whether PRDM16 also controls other gene programs to regulate adipocyte function was unclear. Here, we identify a novel role for PRDM16 in suppressing type I interferon (IFN)-stimulated genes (ISGs), including Stat1, in adipocytes in vitro and in vivo Ectopic activation of type I IFN signaling in brown adipocytes induces mitochondrial dysfunction and reduces uncoupling protein 1 (UCP1) expression...
April 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28404815/the-hepatokine-fgf21-is-crucial-for-peroxisome-proliferator-activated-receptor-%C3%AE-agonist-induced-amelioration-of-metabolic-disorders-in-obese-mice
#19
Tsuyoshi Goto, Mariko Hirata, Yumeko Aoki, Mari Iwase, Haruya Takahashi, Minji Kim, Yongjia Li, Huei-Fen Jheng, Wataru Nomura, Nobuyuki Takahashi, Chu-Sook Kim, Rina Yu, Shigeto Seno, Hideo Matsuda, Megumi Aizawa-Abe, Ken Ebihara, Nobuyuki Itoh, Teruo Kawada
Obesity causes excess fat accumulation in white adipose tissues (WAT) and also in other insulin-responsive organs such as the skeletal muscle, increasing the risk for insulin resistance, which can lead to obesity-related metabolic disorders. Peroxisome proliferator-activated receptor-α (PPARα) is a master regulator of fatty acid oxidation, whose activator is known to improve hyperlipidemia. However, the molecular mechanisms underlying PPARα activator-mediated reduction in adiposity and improvement of metabolic disorders are largely unknown...
April 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28398509/mll3-mll4-are-required-for-cbp-p300-binding-on-enhancers-and-super-enhancer-formation-in-brown-adipogenesis
#20
Binbin Lai, Ji-Eun Lee, Younghoon Jang, Lifeng Wang, Weiqun Peng, Kai Ge
Histone H3K4me1/2 methyltransferases MLL3/MLL4 and H3K27 acetyltransferases CBP/p300 are major enhancer epigenomic writers. To understand how these epigenomic writers orchestrate enhancer landscapes in cell differentiation, we have profiled genomic binding of MLL4, CBP, lineage-determining transcription factors (EBF2, C/EBPβ, C/EBPα, PPARγ), coactivator MED1, RNA polymerase II, as well as epigenome (H3K4me1/2/3, H3K9me2, H3K27me3, H3K36me3, H3K27ac), transcriptome and chromatin opening during adipogenesis of immortalized preadipocytes derived from mouse brown adipose tissue (BAT)...
April 8, 2017: Nucleic Acids Research
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