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Bruce spiegelman

Lawrence Kazak, Edward T Chouchani, Irina G Stavrovskaya, Gina Z Lu, Mark P Jedrychowski, Daniel F Egan, Manju Kumari, Xingxing Kong, Brian K Erickson, John Szpyt, Evan D Rosen, Michael P Murphy, Bruce S Kristal, Steven P Gygi, Bruce M Spiegelman
Brown adipose tissue (BAT) mitochondria exhibit high oxidative capacity and abundant expression of both electron transport chain components and uncoupling protein 1 (UCP1). UCP1 dissipates the mitochondrial proton motive force (Δp) generated by the respiratory chain and increases thermogenesis. Here we find that in mice genetically lacking UCP1, cold-induced activation of metabolism triggers innate immune signaling and markers of cell death in BAT. Moreover, global proteomic analysis reveals that this cascade induced by UCP1 deletion is associated with a dramatic reduction in electron transport chain abundance...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
Serkan Kir, Bruce M Spiegelman
Cachexia, a progressive weight loss in cancer patients that results from tumor-induced energy wasting, is a serious problem that interferes with response to treatment and affects quality of life. Recent studies suggest that thermogenesis of adipose tissues is involved in energy wasting and also point to a link between the atrophy of fat and muscle. Tumor-derived PTHrP has emerged as a key molecule playing multiple roles in cachexia, from fat "browning" factor to potential therapeutic target.
September 2016: Trends in Cancer
Ambre M Bertholet, Lawrence Kazak, Edward T Chouchani, Marta G Bogaczyńska, Ishan Paranjpe, Gabrielle L Wainwright, Alexandre Bétourné, Shingo Kajimura, Bruce M Spiegelman, Yuriy Kirichok
Cold and other environmental factors induce "browning" of white fat depots-development of beige adipocytes with morphological and functional resemblance to brown fat. Similar to brown fat, beige adipocytes are assumed to express mitochondrial uncoupling protein 1 (UCP1) and are thermogenic due to the UCP1-mediated H(+) leak across the inner mitochondrial membrane. However, this assumption has never been tested directly. Herein we patch clamped the inner mitochondrial membrane of beige and brown fat to provide a direct comparison of their thermogenic H(+) leak (IH)...
April 4, 2017: Cell Metabolism
Tina Wenz, Francisca Diaz, Bruce M Spiegelman, Carlos T Moraes
No abstract text is available yet for this article.
December 13, 2016: Cell Metabolism
Lykke Sylow, Jonathan Z Long, Isha A Lokurkar, Xing Zeng, Erik A Richter, Bruce M Spiegelman
Dasatinib (Sprycel) is a tyrosine kinase inhibitor approved for treatment of chronic myeloid leukemia. In this study, we identify dasatinib as a potent inducer of Peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α mRNA. Dasatinib increased PGC-1α mRNA expression up to 6-fold in 3T3-F442A adipocytes, primary adipocytes, and epididymal white adipose tissue from lean and diet-induced obese mice. Importantly, gene expression translated into increased PGC-1α protein content analyzed in melanoma cells and isolated mitochondria from adipocytes...
November 2016: Endocrinology
Xing Zeng, Mark P Jedrychowski, Yi Chen, Sara Serag, Gareth G Lavery, Steve P Gygi, Bruce M Spiegelman
Brown adipocytes display phenotypic plasticity, as they can switch between the active states of fatty acid oxidation and energy dissipation versus a more dormant state. Cold exposure or β-adrenergic stimulation favors the active thermogenic state, whereas sympathetic denervation or glucocorticoid administration promotes more lipid accumulation. Our understanding of the molecular mechanisms underlying these switches is incomplete. Here we found that LSD1 (lysine-specific demethylase 1), a histone demethylase, regulates brown adipocyte metabolism in two ways...
August 15, 2016: Genes & Development
Paul Cohen, Bruce M Spiegelman
The worldwide epidemic of obesity and type 2 diabetes has greatly increased interest in the biology and physiology of adipose tissues. Adipose (fat) cells are specialized for the storage of energy in the form of triglycerides, but research in the last few decades has shown that fat cells also play a critical role in sensing and responding to changes in systemic energy balance. White fat cells secrete important hormone-like molecules such as leptin, adiponectin, and adipsin to influence processes such as food intake, insulin sensitivity, and insulin secretion...
August 15, 2016: Molecular Biology of the Cell
Vassilios J Bezzerides, Colin Platt, Carolin Lerchenmüller, Kaavya Paruchuri, Nul Loren Oh, Chunyang Xiao, Yunshan Cao, Nina Mann, Bruce M Spiegelman, Anthony Rosenzweig
The mechanisms by which exercise mediates its multiple cardiac benefits are only partly understood. Prior comprehensive analyses of the cardiac transcriptional components and microRNAs dynamically regulated by exercise suggest that the CBP/p300-interacting protein CITED4 is a downstream effector in both networks. While CITED4 has documented functional consequences in neonatal cardiomyocytes in vitro, nothing is known about its effects in the adult heart. To investigate the impact of cardiac CITED4 expression in adult animals, we generated transgenic mice with regulated, cardiomyocyte-specific CITED4 expression...
June 16, 2016: JCI Insight
Jonathan Z Long, Katrin J Svensson, Leslie A Bateman, Hua Lin, Theodore Kamenecka, Isha A Lokurkar, Jesse Lou, Rajesh R Rao, Mi Ra Chang, Mark P Jedrychowski, Joao A Paulo, Steven P Gygi, Patrick R Griffin, Daniel K Nomura, Bruce M Spiegelman
Brown and beige adipocytes are specialized cells that express uncoupling protein 1 (UCP1) and dissipate chemical energy as heat. These cells likely possess alternative UCP1-independent thermogenic mechanisms. Here, we identify a secreted enzyme, peptidase M20 domain containing 1 (PM20D1), that is enriched in UCP1(+) versus UCP1(-) adipocytes. We demonstrate that PM20D1 is a bidirectional enzyme in vitro, catalyzing both the condensation of fatty acids and amino acids to generate N-acyl amino acids and also the reverse hydrolytic reaction...
July 14, 2016: Cell
Edward T Chouchani, Lawrence Kazak, Mark P Jedrychowski, Gina Z Lu, Brian K Erickson, John Szpyt, Kerry A Pierce, Dina Laznik-Bogoslavski, Ramalingam Vetrivelan, Clary B Clish, Alan J Robinson, Steve P Gygi, Bruce M Spiegelman
No abstract text is available yet for this article.
August 18, 2016: Nature
Miguel Soares Conceição, Mara Patricia Traina Chacon-Mikahil, Guilherme Defante Telles, Cleiton Augusto Libardi, Edson Manoel Mendes Júnior, Felipe Cassaro Vechin, André Luis Lugnani DE Andrade, Arthur Fernandes Gáspari, Patrícia Chakur Brum, Cláudia Regina Cavaglieri, Sara Serag, Bruce M Spiegelman, John A Hawley, Donny M Camera
INTRODUCTION: Exercise performed with blood flow restriction simultaneously enhances the acute responses to both myogenic and mitochondrial pathways with roles in training adaptation. We investigated isoform-specific gene expression of the peroxisome proliferator-activated receptor gamma coactivator 1 and selected target genes and proteins regulating skeletal muscle training adaptation. METHODS: Nine healthy, untrained males participated in a randomized, counterbalanced, crossover design in which each subject completed a bout of low-intensity endurance exercise performed with blood flow restriction (15 min cycling at 40% of V˙O2peak, BFR-EE), endurance exercise (30 min cycling at 70% of V˙O2peak, EE), or resistance exercise (4 × 10 repetitions of leg press at 70% of one-repetition maximum) separated by at least 1 wk of recovery...
September 2016: Medicine and Science in Sports and Exercise
Edward T Chouchani, Lawrence Kazak, Mark P Jedrychowski, Gina Z Lu, Brian K Erickson, John Szpyt, Kerry A Pierce, Dina Laznik-Bogoslavski, Ramalingam Vetrivelan, Clary B Clish, Alan J Robinson, Steve P Gygi, Bruce M Spiegelman
Brown and beige adipose tissues can dissipate chemical energy as heat through thermogenic respiration, which requires uncoupling protein 1 (UCP1). Thermogenesis from these adipocytes can combat obesity and diabetes, encouraging investigation of factors that control UCP1-dependent respiration in vivo. Here we show that acutely activated thermogenesis in brown adipose tissue is defined by a substantial increase in levels of mitochondrial reactive oxygen species (ROS). Remarkably, this process supports in vivo thermogenesis, as pharmacological depletion of mitochondrial ROS results in hypothermia upon cold exposure, and inhibits UCP1-dependent increases in whole-body energy expenditure...
April 7, 2016: Nature
Katrin J Svensson, Jonathan Z Long, Mark P Jedrychowski, Paul Cohen, James C Lo, Sara Serag, Serkan Kir, Kosaku Shinoda, Julia A Tartaglia, Rajesh R Rao, Alain Chédotal, Shingo Kajimura, Steven P Gygi, Bruce M Spiegelman
Activation of brown and beige fat can reduce obesity and improve glucose homeostasis through nonshivering thermogenesis. Whether brown or beige fat also secretes paracrine or endocrine factors to promote and amplify adaptive thermogenesis is not fully explored. Here we identify Slit2, a 180 kDa member of the Slit extracellular protein family, as a PRDM16-regulated secreted factor from beige fat cells. In isolated cells and in mice, full-length Slit2 is cleaved to generate several smaller fragments, and we identify an active thermogenic moiety as the C-terminal fragment...
March 8, 2016: Cell Metabolism
Amanda M Fretts, Dariush Mozaffarian, David S Siscovick, Irena B King, Barbara McKnight, Bruce M Psaty, Eric B Rimm, Colleen Sitlani, Frank M Sacks, Xiaoling Song, Nona Sotoodehnia, Donna Spiegelman, Rozenn N Lemaitre
BACKGROUND: Not much is known about the relations of circulating saturated fatty acids (SFAs), which are influenced by both metabolic and dietary determinants, with total and cause-specific mortality. OBJECTIVE: We examined the associations of plasma phospholipid SFAs with total and cause-specific mortality among 3941 older adults from the Cardiovascular Health Study, a population-based prospective study of adults aged ≥65 y who were followed from 1992 through 2011...
February 2016: Journal of Nutrition
Shingo Kajimura, Bruce M Spiegelman, Patrick Seale
Since brown adipose tissue (BAT) dissipates energy through UCP1, BAT has garnered attention as a therapeutic intervention for obesity and metabolic diseases including type 2 diabetes. As we better understand the physiological roles of classical brown and beige adipocytes, it is becoming clear that BAT is not simply a heat-generating organ. Increased beige fat mass in response to a variety of external/internal cues is associated with significant improvements in glucose and lipid homeostasis that may not be entirely mediated by UCP1...
October 6, 2015: Cell Metabolism
Mark P Jedrychowski, Christiane D Wrann, Joao A Paulo, Kaitlyn K Gerber, John Szpyt, Matthew M Robinson, K Sreekumaran Nair, Steven P Gygi, Bruce M Spiegelman
Exercise provides many health benefits, including improved metabolism, cardiovascular health, and cognition. We have shown previously that FNDC5, a type I transmembrane protein, and its circulating form, irisin, convey some of these benefits in mice. However, recent reports questioned the existence of circulating human irisin both because human FNDC5 has a non-canonical ATA translation start and because of claims that many human irisin antibodies used in commercial ELISA kits lack required specificity. In this paper we have identified and quantitated human irisin in plasma using mass spectrometry with control peptides enriched with heavy stable isotopes as internal standards...
October 6, 2015: Cell Metabolism
Paul Cohen, Bruce M Spiegelman
The epidemic of obesity and type 2 diabetes has increased interest in pathways that affect energy balance in mammalian systems. Brown fat, in all of its dimensions, can increase energy expenditure through the dissipation of chemical energy in the form of heat, using mitochondrial uncoupling and perhaps other pathways. We discuss here some of the thermodynamic and cellular aspects of recent progress in brown fat research. This includes studies of developmental lineages of UCP1(+) adipocytes, including the discovery of beige fat cells, a new thermogenic cell type...
July 2015: Diabetes
Patrick Schrauwen, Wouter D van Marken Lichtenbelt, Bruce M Spiegelman
The recent recognition that humans possess active depots of brown adipose tissue has boosted the interest in this tissue as a potential target for the prevention and treatment of obesity and related metabolic disorders. Furthermore, it was also revealed that brown adipose tissue (BAT) in humans may consist of so-called beige or brite adipocytes. So far, cold exposure is recognised as the strongest activator of BAT in humans, but there is much ongoing research focused on finding alternative activators of BAT...
August 2015: Diabetologia
Xiaojun Liu, Junjie Xiao, Han Zhu, Xin Wei, Colin Platt, Federico Damilano, Chunyang Xiao, Vassilios Bezzerides, Pontus Boström, Lin Che, Chunxiang Zhang, Bruce M Spiegelman, Anthony Rosenzweig
Exercise induces physiological cardiac growth and protects the heart against pathological remodeling. Recent work suggests exercise also enhances the heart's capacity for repair, which could be important for regenerative therapies. While microRNAs are important in certain cardiac pathologies, less is known about their functional roles in exercise-induced cardiac phenotypes. We profiled cardiac microRNA expression in two distinct models of exercise and found microRNA-222 (miR-222) was upregulated in both. Downstream miR-222 targets modulating cardiomyocyte phenotypes were identified, including HIPK1 and HMBOX1...
April 7, 2015: Cell Metabolism
Brian A Irving, Ian R Lanza, Gregory C Henderson, Rajesh R Rao, Bruce M Spiegelman, K Sreekumaran Nair
CONTEXT: Skeletal muscle from sedentary older adults exhibits reduced mitochondrial abundance and oxidative capacity. OBJECTIVE: The primary objective was to determine whether 8 weeks of combined training (CT) has a more robust effect than endurance training (ET) or resistance training (RT) on mitochondrial physiology in healthy young (18-30 years) and older (≥ 65 years) adults. INTERVENTION: Thirty-four young and 31 older adults were randomly assigned to 8 weeks of ET, RT, and control/CT...
April 2015: Journal of Clinical Endocrinology and Metabolism
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