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https://www.readbyqxmd.com/read/29235464/syk-kinase-mediates-brown-fat-differentiation-and-activation
#1
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/29210120/endogenous-peripheral-hydrogen-sulfide-is-propyretic-its-permissive-role-in-brown-adipose-tissue-thermogenesis-in-rats
#2
Renato N Soriano, Sara P Braga, Jéssica S C Breder, Marcelo E Batalhao, Gabriela R Oliveira-Pelegrin, Luiz Fernando R Ferreira, Maria José A Rocha, Evelin C Carnio, Luiz G S Branco
In recent years hydrogen sulfide (H2 S) has been reported as a gaseous modulator acting in several tissues in health and disease. In systemic inflammation animal models, plasma H2 S concentration increases in response to endotoxin (bacterial lipopolysaccharide, LPS). The most striking response in the acute phase reaction of systemic inflammation is fever, but reports of the peripheral action of H2 S on this thermoregulatory response are not found. We aimed at investigating whether endogenous systemic H2 S modulates LPS-induced fever...
December 6, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29209779/central-regulation-of-brown-adipose-tissue-thermogenesis-and-energy-homeostasis-dependent-on-food-availability
#3
REVIEW
Yoshiko Nakamura, Kazuhiro Nakamura
Energy homeostasis of mammals is maintained by balancing energy expenditure within the body and energy intake through feeding. Several lines of evidence indicate that brown adipose tissue (BAT), a sympathetically activated thermogenic organ, turns excess energy into heat to maintain the energy balance in rodents and humans, in addition to its thermoregulatory role for the defense of body core temperature in cold environments. Elucidating the central circuit mechanism controlling BAT thermogenesis dependent on nutritional conditions and food availability in relation to energy homeostasis is essential to understand the etiology of symptoms caused by energy imbalance, such as obesity...
December 5, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29203476/ucp1-deficiency-increases-adipose-tissue-monounsaturated-fatty-acid-synthesis-and-trafficking-to-the-liver
#4
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/29200996/regulation-of-brown-adipose-tissue-activity-by-interoceptive-cns-pathways-the-interaction-between-brain-and-periphery
#5
Otto Muzik, Vaibhav A Diwadkar
To maintain thermal homeostasis, specific thermogenic tissues are under the control of central thermoregulatory networks that regulate the body's response to thermal challenges. One of these mechanisms involves non-shivering thermogenesis in brown adipose tissue (BAT), which is activated in cold environments in order to defend the body against physical damage as a result of hypothermia. The objective of our study was to assess the interaction between CNS thermoregulatory pathways and sympathetic innervation in BAT during a cold exposure paradigm...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29170642/muscle-non-shivering-thermogenesis-and-its-role-in-the-evolution-of-endothermy
#6
REVIEW
Julia Nowack, Sylvain Giroud, Walter Arnold, Thomas Ruf
The development of sustained, long-term endothermy was one of the major transitions in the evolution of vertebrates. Thermogenesis in endotherms does not only occur via shivering or activity, but also via non-shivering thermogenesis (NST). Mammalian NST is mediated by the uncoupling protein 1 in the brown adipose tissue (BAT) and possibly involves an additional mechanism of NST in skeletal muscle. This alternative mechanism is based on Ca(2+)-slippage by a sarcoplasmatic reticulum Ca(2+)-ATPase (SERCA) and is controlled by the protein sarcolipin...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29153407/brown-fat-akt2-is-a-cold-induced-kinase-that-stimulates-chrebp-mediated-de-novo-lipogenesis-to-optimize-fuel-storage-and-thermogenesis
#7
Joan Sanchez-Gurmaches, Yuefeng Tang, Naja Zenius Jespersen, Martina Wallace, Camila Martinez Calejman, Sharvari Gujja, Huawei Li, Yvonne J K Edwards, Christian Wolfrum, Christian M Metallo, Søren Nielsen, Camilla Scheele, David A Guertin
Brown adipose tissue (BAT) is a therapeutic target for metabolic diseases; thus, understanding its metabolic circuitry is clinically important. Many studies of BAT compare rodents mildly cold to those severely cold. Here, we compared BAT remodeling between thermoneutral and mild-cold-adapted mice, conditions more relevant to humans. Although BAT is renowned for catabolic β-oxidative capacity, we find paradoxically that the anabolic de novo lipogenesis (DNL) genes encoding ACLY, ACSS2, ACC, and FASN were among the most upregulated by mild cold and that, in humans, DNL correlates with Ucp1 expression...
November 15, 2017: Cell 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/29133865/cold-acclimation-causes-fiber-type-specific-responses-in-glucose-and-fat-metabolism-in-rat-skeletal-muscles
#9
Diane M Sepa-Kishi, Yass Sotoudeh-Nia, Ayesha Iqbal, George Bikopoulos, Rolando B Ceddia
This study investigated fiber type-specific metabolic responses and the molecular mechanisms that regulate glucose and fat metabolism in oxidative and glycolytic muscles upon cold acclimation. Male Wistar rats were exposed to cold (4 °C) for 7 days, and then glycogen synthesis and content, glucose and palmitate oxidation, and the molecular mechanisms underlying these metabolic pathways were assessed in soleus (Sol), extensor digitorum longus (EDL), and epitrochlearis (Epit) muscles. Cold acclimation increased glycogen synthesis, glycogen content, glucose oxidation, and reduced glycogen synthase (GS) phosphorylation only in Sol muscles...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29118013/restricting-glycolysis-impairs-brown-adipocyte-glucose-and-oxygen-consumption
#10
Sally Winther, Marie S Isidor, Astrid L Basse, Nina Skjoldborg, Amanda Cheung, Bjørn Quistorff, Jacob B Hansen
During thermogenic activation, brown adipocytes take up large amounts of glucose. In addition, cold stimulation leads to an upregulation of glycolytic enzymes. Here we have investigated the importance of glycolysis for brown adipocyte glucose consumption and thermogenesis. Using siRNA-mediated knockdown in mature adipocytes, we explored the effect of glucose transporters and glycolytic enzymes on brown adipocyte functions such as consumption of glucose and oxygen. Basal oxygen consumption in brown adipocytes was equally dependent on glucose and fatty acid oxidation, whereas isoproterenol (ISO)-stimulated respiration was fueled mainly by fatty acids, with a significant contribution from glucose oxidation...
November 7, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29113988/seasonal-variation-in-the-thermal-responses-to-changing-environmental-temperature-in-the-world-s-northernmost-landbird
#11
Andreas Nord, Lars P Folkow
Arctic homeotherms counter challenges at high latitudes using a combination of seasonal adjustments in pelage/plumage, fat deposition, and intricate thermoregulatory adaptations. However, there are still gaps in our understanding of their thermal responses to cold, particularly in Arctic birds. Here, we have studied the potential use of local heterothermy (i.e., tissue cooling that can contribute to significantly lower heat loss rate) in Svalbard ptarmigan (Lagopus muta hyperborea) - the world's northernmost landbird...
November 7, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29078316/reconstitution-of-ucp1-using-crispr-cas9-in-the-white-adipose-tissue-of-pigs-decreases-fat-deposition-and-improves-thermogenic-capacity
#12
Qiantao Zheng, Jun Lin, Jiaojiao Huang, Hongyong Zhang, Rui Zhang, Xueying Zhang, Chunwei Cao, Catherine Hambly, Guosong Qin, Jing Yao, Ruigao Song, Qitao Jia, Xiao Wang, Yongshun Li, Nan Zhang, Zhengyu Piao, Rongcai Ye, John R Speakman, Hongmei Wang, Qi Zhou, Yanfang Wang, Wanzhu Jin, Jianguo Zhao
Uncoupling protein 1 (UCP1) is localized on the inner mitochondrial membrane and generates heat by uncoupling ATP synthesis from proton transit across the inner membrane. UCP1 is a key element of nonshivering thermogenesis and is most likely important in the regulation of body adiposity. Pigs (Artiodactyl family Suidae) lack a functional UCP1 gene, resulting in poor thermoregulation and susceptibility to cold, which is an economic and pig welfare issue owing to neonatal mortality. Pigs also have a tendency toward fat accumulation, which may be linked to their lack of UCP1, and thus influences the efficiency of pig production...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29075844/changes-in-thermoregulation-and-monoamine-release-in-freely-moving-rats-during-cold-exposure-and-inhibition-of-the-ventromedial-dorsomedial-or-posterior-hypothalamus
#13
Takayuki Ishiwata, Benjamin N Greenwood
The hypothalamus is critical for regulating thermogenesis, but the role of monoamines in specific hypothalamic subregions in thermogenesis is not thoroughly established. The purpose of this study was to confirm changes of body temperature (T b) and thermoregulatory parameters upon inhibition of neural activity in hypothalamic subregions in freely moving rats. In addition, the pattern of monoamine release in these nuclei was measured during active thermoregulation using microdialysis. Tetrodotoxin (TTX) was perfused into the ventromedial hypothalamus (VMH), dorsomedial hypothalamus (DMH), or posterior hypothalamus (PH) at two different ambient temperatures (5 or 23 °C)...
October 26, 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/29070564/no-metabolic-effects-of-mustard-allyl-isothiocyanate-compared-with-placebo-in-men
#14
Mirjam Langeveld, Chong Yew Tan, Maarten R Soeters, Samuel Virtue, Laura Pe Watson, Peter R Murgatroyd, Graeme K Ambler, Santiago Vidal-Puig, Krishna V Chatterjee, Antonio Vidal-Puig
Background: Induction of nonshivering thermogenesis can be used to influence energy balance to prevent or even treat obesity. The pungent component of mustard, allyl-isothiocyanate (AITC), activates the extreme cold receptor transient receptor potential channel, subfamily A, member 1 and may thus induce energy expenditure and metabolic changes.Objective: The objective of our study was to evaluate the potential of mustard AITC to induce thermogenesis (primary outcome) and alter body temperature, cold and hunger sensations, plasma metabolic parameters, and energy intake (secondary outcomes)...
November 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/29058611/adiponectin-is-required-for-maintaining-normal-body-temperature-in-a-cold-environment
#15
Qiong Wei, Jong Han Lee, Hongying Wang, Odelia Y N Bongmba, Chia-Shan Wu, Geetali Pradhan, Zilin Sun, Lindsey Chew, Mandeep Bajaj, Lawrence Chan, Robert S Chapkin, Miao-Hsueh Chen, Yuxiang Sun
BACKGROUND: Thermogenic impairment promotes obesity and insulin resistance. Adiponectin is an important regulator of energy homeostasis. While many beneficial metabolic effects of adiponectin resemble that of activated thermogenesis, the role of adiponectin in thermogenesis is not clear. In this study, we investigated the role of adiponectin in thermogenesis using adiponectin-null mice (Adipoq -/-). METHODS: Body composition was measured using EchoMRI. Metabolic parameters were determined by indirect calorimetry...
October 23, 2017: BMC Physiology
https://www.readbyqxmd.com/read/29052591/targeting-thermogenesis-in-brown-fat-and-muscle-to-treat-obesity-and-metabolic-disease
#16
REVIEW
Matthias J Betz, Sven Enerbäck
Brown fat is emerging as an interesting and promising target for therapeutic intervention in obesity and metabolic disease. Activation of brown fat in humans is associated with marked improvement in metabolic parameters such as levels of free fatty acids and insulin sensitivity. Skeletal muscle is another important organ for thermogenesis, with the capacity to induce energy-consuming futile cycles. In this Review, we focus on how these two major thermogenic organs - brown fat and muscle - act and cooperate to maintain normal body temperature...
October 23, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/29046921/pioglitazone-reduces-cold-induced-brown-fat-glucose-uptake-despite-induction-of-browning-in-cultured-human-adipocytes-a-randomised-controlled-trial-in-humans
#17
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
AIMS/HYPOTHESIS: Increasing brown adipose tissue (BAT) activity is a possible therapeutic strategy to increase energy expenditure and glucose and lipid clearance to ameliorate obesity and associated comorbidities. The thiazolidinedione (TZD) class of glucose-lowering drugs increase BAT browning in preclinical experimental models but whether these actions extend to humans in vivo is unknown. The aim of this study was to determine the effect of pioglitazone treatment on adipocyte browning and adaptive thermogenesis in humans...
October 18, 2017: Diabetologia
https://www.readbyqxmd.com/read/29040448/male-brown-fat-specific-double-knockout-of-igfir-ir-atrophy-mitochondrial-fission-failure-impaired-thermogenesis-and-obesity
#18
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/29037389/lower-critical-temperature-and-cold-induced-thermogenesis-of-lean-and-overweight-humans-are-inversely-related-to-body-mass-and-basal-metabolic-rate
#19
Kimberly J Nahon, Mariëtte R Boon, Fleur Doornink, Ingrid M Jazet, Patrick C N Rensen, Gustavo Abreu-Vieira
It is colloquially stated that body size plays a role in the human response to cold, but the magnitude and details of this interaction are unclear. To explore the inherent influence of body size on cold-exposed metabolism, we investigated the relation between body composition and resting metabolic rate in humans at thermoneutrality and during cooling within the nonshivering thermogenesis range. Body composition and resting energy expenditure were measured in 20 lean and 20 overweight men at thermoneutrality and during individualized cold exposure...
October 2017: Journal of Thermal Biology
https://www.readbyqxmd.com/read/29033896/the-influence-of-a-kdt501-a-novel-isohumulone-on-adipocyte-function-in-humans
#20
Brian S Finlin, Beibei Zhu, Bernard P Kok, Cristina Godio, Philip M Westgate, Neile Grayson, Robert Sims, Jeffrey S Bland, Enrique Saez, Philip A Kern
OBJECTIVE: In a phase II clinical trial in nine obese, insulin-resistant humans, we observed that treatment with KDT501, a novel isohumulone drug, increased total and high-molecular weight (HMW) adiponectin in plasma. The objective was to determine whether KDT501 increased adiponectin secretion from subcutaneous white adipose tissue (SC WAT) and the underlying mechanism(s). METHODS: Nine obese participants with either prediabetes or with normal glucose tolerance plus three features of metabolic syndrome were part of the study...
2017: Frontiers in Endocrinology
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