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UCP Thermogenesis

Michael J Gaudry, Martin Jastroch
Uncoupling proteins (UCPs) belong to the mitochondrial anion carrier superfamily and catalyze important metabolic functions at the mitochondrial inner membrane. While the thermogenic role of UCP1 in brown fat of eutherian mammals is well established, the molecular functions of UCP1 in ectothermic vertebrates and of other UCP paralogs remain less clear. Here, we critically discuss the existence of brain UCPs and their potential roles. Applying phylogenetic classification of novel UCPs, we summarize the evidence for brain UCP1 among vertebrates, the role of UCP2 in specific brain areas, and the existence of brain-specific UCPs...
December 21, 2018: Neuroscience Letters
Yun Li, Xing Wang, Fei Wang, Lianghui You, Pengfei Xu, Yan Cao, Ling Chen, Juan Wen, Xirong Guo, Xianwei Cui, Chenbo Ji
OBJECTIVES: Currently, brown adipose tissue (BAT) is a therapeutic target in obesity and diabetes, but the mechanism of BAT activation remains unclear. Because increasing emphasis has been placed on the role of intracellular peptides in biological processes, we conducted a study to gain insight into the mechanism of BAT activation by using a peptidomic approach and then attempted to identify peptides that are capable of activating BAT. METHODS: In the present study, we generated the peptidomic profile of the intracellular peptides in brown adipocytes treated with forskolin (FSK) using a peptidomic approach...
November 1, 2018: Journal of Cellular Physiology
Karim S Echtay, Martin Bienengraeber, Peter Mayinger, Simone Heimpel, Edith Winkler, Doerthe Druhmann, Karina Frischmuth, Frits Kamp, Shu-Gui Huang
The uncoupling protein (UCP1) is a proton (H+ ) transporter in the mitochondrial inner membrane. By dissipating the electrochemical H+ gradient, UCP1 uncouples respiration from ATP synthesis, which drives an increase in substrate oxidation via the TCA cycle flux that generates more heat. The mitochondrial uncoupling-mediated non-shivering thermogenesis in brown adipose tissue is vital primarily to mammals, such as rodents and new-born humans, but more recently additional functions in adult humans have been described...
November 1, 2018: Archives of Biochemistry and Biophysics
Wojciech Danysz, Kang Jinlai, Fugang Li
"Browning" i. e. the transformation of white adipose tissue into brown-like adipose tissue could induce efficient burning of excess fat reserves via induction of non-shivering thermogenesis. For example, activation of ß3 adrenergic receptors has been show to induce such changes, however, it is still not clear, how long after termination of such a treatment, beneficial effects might be maintained. To address this question, we treated rats s.c. for 2 weeks with the ß3 agonist CL-316,243 at 1 mg/kg and assessed interscapular brown fat and inguinal white fat pads weight, UCP-1 (a marker for the brown-like fat phenotype) using immunohistochemistry and H&E staining, at different intervals after treatment termination...
September 6, 2018: Drug Research
Hui Chen, Lei Xiong, Ning Wang, Xin Liu, Wenbing Hu, Zhanwei Yang, Yan Jiang, Guodong Zheng, Kehui Ouyang, Wenjun Wang
The present study aimed to explore the potent molecular mechanisms behind the hypoglycemic effect of Chimonanthus nitens Oliv. leaf extract (COE) in combination with a high-glucose-fat diet-fed and streptozotocin-induced diabetic mouse model. COE (50 and 200 mg per kg body weight per day) was given to the diabetic-model mice by intragastric administration for 4 weeks. It was found that the fasting blood glucose level (FBG), serum insulin level (FINS), and insulin sensitivity index (ISI) were significantly improved in the COE-treated diabetic-model mice...
September 19, 2018: Food & Function
Perla P Argentato, Helena de Cássia César, Débora Estadella, Luciana P Pisani
Brown adipose tissue (BAT) has recently been given more attention for the part it plays in obesity. BAT can generate great amounts of heat through thermogenesis by the activation of uncoupling protein 1 (UCP-1), which can be regulated by many environmental factors such as diet. Moreover, the build-up of BAT relates to maternal nutritional changes during pregnancy and lactation. However, at present, there is a limited number of studies looking at maternal nutrition and BAT development, and it seems that the research trend in this field has been considerably declining since the 1980s...
September 2018: British Journal of Nutrition
Yan Tang, Yi He, Chen Li, Wenjuan Mu, Ying Zou, Conghui Liu, Shuwen Qian, Fuchuang Zhang, Jiabao Pan, Yina Wang, Haiyan Huang, Dongning Pan, Pengyuan Yang, Ju Mei, Rong Zeng, Qi-Qun Tang
Pericardial adipose tissue, which comprises both epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT), has recently been recognized as a novel factor in the pathophysiology of cardiovascular diseases, especially coronary artery disease (CAD). The goal of this study was to evaluate differences in the brown-like characteristic and proteome among human EAT, PAT, and subcutaneous adipose tissue (SAT) to identify candidate molecules causing CAD. Uncoupling protein 1 (UCP-1) and other brown-related proteins were highly expressed in pericardial adipose tissue but was weakly expressed in SAT from the same non-CAD patient...
2018: Cell Discovery
Shuyuan Chen, Raul A Bastarrachea, Jin-Song Shen, Antonio Laviada-Nagel, Ernesto Rodriguez-Ayala, Edna J Nava-Gonzalez, Pintong Huang, Ralph A DeFronzo, Jack W Kent, Paul A Grayburn
Here we present our progress in inducing an ectopic brown adipose tissue (BAT) phenotype in skeletal muscle (SKM) as a potential gene therapy for obesity and its comorbidities. We used ultrasound-targeted microbubble destruction (UTMD), a novel targeted, non-viral approach to gene therapy, to deliver genes in the BAT differentiation pathway into rodent SKM to engineer a thermogenic BAT phenotype with ectopic mUCP-1 overexpression. In parallel, we performed a second protocol using wild-type Ucp-1-null knockout mice to test whether the effects of the gene therapy are UCP-1 dependent...
October 2018: Gene Therapy
Georgios K Dimitriadis, Raghu Adya, Bee K Tan, Terence A Jones, Vinod S Menon, Manjunath Ramanjaneya, Gregory Kaltsas, Alexander D Miras, Harpal S Randeva
The role of brown adipose tissue (BAT) in pathological states of energy homeostasis and impaired adipocyte function, such as obesity has been a major area of research interest in recent years. Herein, we sought to determine the direct effects of adipokines, visfatin and leptin on BAT thermogenesis. The effects of mouse recombinant visfatin, nicotinamide mononucleotide (NMN) and leptin with or without FK866 were studied on differentiated T37i cells. Treated cells were analyzed for key genes and proteins regulating BAT [UCP-1, PRD1-BF1-RIZ1 homologous domain-containing 16 (PRDM-16), PPARgamma-coactivator-1alpha (PGC-1α) and receptor-interacting protein 140 (RIP-140)] using quantitative PCR and western blot analysis...
July 27, 2018: Cytokine
Kei Zaitsu, Saki Noda, Akira Iguchi, Yumi Hayashi, Tomomi Ohara, Yuya Kimura, Yuta Koketsu, Tomoko Kosaki, Maiko Kusano, Takako Sato, Tetsuya Ishikawa, Hitoshi Tsuchihashi, Koichi Suzuki, Akira Ishii
AIMS: Serotonin syndrome (SS) is an adverse outcome of selective serotonin reuptake inhibitors, though its mechanism is not understood and there is no specific clinical biomarker. In this article, metabolic profiles of the SS model rats and causes of metabolome disruption were investigated. MAIN METHODS: Gas chromatography-tandem mass spectrometry (GC/MS/MS)-based metabolomics, clinical biomarker measurements and qRT-PCR analysis for UCP-3 in skeletal muscles were performed...
August 15, 2018: Life Sciences
Tanila Wood Dos Santos, Jonatan Miranda, Lucimara Teixeira, Ana Aiastui, Ander Matheu, Alessandra Gambero, María P Portillo, Marcelo Lima Ribeiro
SCOPE: The potential effects of yerba mate (YM) on mitochondrial biogenesis and thermogenesis are evaluated. METHODS AND RESULTS: The in vitro effects of YM on mitochondrial respiration are assessed in C2C12 cells. The expression of genes related to mitochondrial biogenesis and thermogenesis are analyzed by quantitative PCR. The in vivo experiments are performed on mice fed a high-fat diet (HFD) and treated with YM extract. Indirect calorimetry was performed, and the expression of genes and proteins related to mitochondrial biogenesis, thermogenesis, and de novo lipogenesis is determined by quantitative PCR and western blot...
May 31, 2018: Molecular Nutrition & Food Research
Éva Szentirmai, Levente Kapás
We previously identified brown adipose tissue (BAT) as a source of sleep-inducing signals. Pharmacological activation of BAT enhances sleep while sleep loss leads to increased BAT thermogenesis. Recovery sleep after sleep loss is diminished in mice that lack uncoupling protein 1 (UCP-1), and also in wild-type (WT) mice after sensory denervation of the BAT. Systemic inflammation greatly affects metabolism and the function of adipose tissue, and also induces characteristic sleep responses. We hypothesized that sleep responses to acute inflammation are mediated by BAT-derived signals...
2018: PloS One
Kellen C da Cruz Rodrigues, Rodrigo M Pereira, Thaís D P de Campos, Rodrigo F de Moura, Adelino S R da Silva, Dennys E Cintra, Eduardo R Ropelle, José R Pauli, Michel B de Araújo, Leandro P de Moura
Obesity is a public health issue that affects more than 600 million adults worldwide. The disease is characterized by fat accumulation, mainly in the abdominal area. The human body is mainly composed of two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT); however, the browning process generates a different type of brown fat-like adipocyte in WAT, which similar to BAT has thermogenic capacity by activating UCP-1. The hypothalamic arcuate nucleus plays an important role in WAT browning via POMC neurons, which are influenced by synergistic insulin and leptin signaling...
2018: Frontiers in Cellular Neuroscience
Jia Li, Quanyu Yang, Zhenzhong Bai, Wenhua Zhou, Gregg L Semenza, Ri-Li Ge
The plateau pika (Ochotona curzoniae), one of the indigenous animals of the Qinghai-Tibet Plateau, is adapted to life in a cold and hypoxic environment. We conducted a series of genomic, proteomic and morphological studies to investigate whether changes in energy metabolism contribute to adaptation of the plateau pika to cold stress by analyzing summer and winter cohorts. The winter group showed strong morphological and histological features of brown adipose tissue (BAT) in subcutaneous white adipose tissue (sWAT)...
June 2, 2018: Biochemical and Biophysical Research Communications
Diana Vargas, Carolina López, Edward Acero, Edgar Benitez, Angélica Wintaco, Jaime Camacho, Marisol Carreño, Juan Umaña, Daniela Jimenez, Said Díaz, Fernando Lizcano
The anatomical location of adipose tissue might have direct implications for its functionality and risk of cardiovascular disease. Adipose tissue surrounding blood vessels may be thermogenically more active in specific areas of the body, releasing substances that regulate vascular metabolism. In humans, the phenotypic characteristics of adipose tissue surrounding the aorta and the cardiovascular disease risk that it might entail remain largely unknown. Here, we compared thermogenesis-related molecular features of human periaortic adipose tissue samples with those of subcutaneous adipose tissue, obtained by sternotomy from 42 patients undergoing cardiovascular surgery...
2018: PloS One
Hiroshi Mikamo, Meizi Jiang, Mahito Noro, Yasuo Suzuki, Nobuyuki Hiruta, Hiroyuki Unoki-Kubota, Wolfgang J Schneider, Hideaki Bujo
The upregulation of brown or brown-like beige adipocytes is a potential strategy for the prevention or treatment of diabetes and coronary artery diseases in obese patients. Epicardial adipose tissue (EAT) differs significantly from subcutaneous fat tissue (SAT) in metabolic properties. To investigate properties of EAT further, thermogenesis gene expression was investigated in human autopsy and murine samples, and adipocytes differentiated from EAT mesenchymal cells. Subsequently, analyzed EAT volume alterations were observed to be associated with weight reduction in obese patients by imaging...
May 2018: Molecular Medicine Reports
Nathaly Anto Michel, Christian Colberg, Konrad Buscher, Björn Sommer, Akula Bala Pramod, Erik Ehinger, Bianca Dufner, Natalie Hoppe, Katharina Pfeiffer, Timoteo Marchini, Florian Willecke, Peter Stachon, Ingo Hilgendorf, Timo Heidt, Constantin von Zur Muhlen, Dominik von Elverfeldt, Dietmar Pfeifer, Roland Schüle, Ulrich Kintscher, Sebastian Brachs, Klaus Ley, Christoph Bode, Andreas Zirlik, Dennis Wolf
RATIONALE: The coincidence of inflammation and metabolic derangements in obese adipose tissue has sparked the concept of met-inflammation. Previous observations, however, suggest that inflammatory pathways may not ultimately cause dysmetabolism. OBJECTIVE: We have revisited the relationship between inflammation and metabolism by testing the role of TRAF (tumor necrosis receptor-associated factor)-1, an inhibitory adapter of inflammatory signaling of TNF (tumor necrosis factor)-α, IL (interleukin)-1β, and TLRs (toll-like receptors)...
March 2, 2018: Circulation Research
Gabriel Macher, Melanie Koehler, Anne Rupprecht, Jürgen Kreiter, Peter Hinterdorfer, Elena E Pohl
Mitochondrial membrane uncoupling protein 3 (UCP3) is not only expressed in skeletal muscle and heart, but also in brown adipose tissue (BAT) alongside UCP1, which facilitates a proton leak to support non-shivering thermogenesis. In contrast to UCP1, the transport function and molecular mechanism of UCP3 regulation are poorly investigated, although it is generally agreed upon that UCP3, analogous to UCP1, transports protons, is activated by free fatty acids (FFAs) and is inhibited by purine nucleotides (PNs)...
March 2018: Biochimica et biophysica acta. Biomembranes
Y He, N Ma, M Tang, Z-L Jiang, H Liu, J Mei
OBJECTIVE: Growing evidence has identified that excessive accumulation of pericardial adipose tissues (PAT) and epicardial adipose tissues (EAT) is associated with atrial fibrillation (AF) development. Moreover, beige adipocytes, present in PAT and EAT, have been proved beneficial in consumption of fatty acid and promotion of weight lose by nonshivering thermogenesis. The objective of this prospective, observational study was to reveal the potential association between beige adipocytes and AF development...
October 2017: European Review for Medical and Pharmacological Sciences
Vanesa Viana-Huete, Carlos Guillén, Gema García, Silvia Fernández, Ana García-Aguilar, C R Kahn, Manuel Benito
It is unknown how the lack of insulin receptor (IR)/insulinlike growth factor I receptor (IGFIR) in a tissue-specific manner affects brown fat development and mitochondrial integrity and function, as well as its effect on the redistribution of the adipose organ and the metabolic status. To address this important issue, we developed IR/IGFIR double-knockout (DKO) in a brown adipose tissue-specific manner. Lack of those receptors caused severe brown fat atrophy, 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...
January 1, 2018: Endocrinology
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