Dynamic regulation of genes involved in mitochondrial DNA replication and transcription during mouse brown fat cell differentiation and recruitment.
Maria Murholm,Karen Dixen,Klaus Qvortrup,Lillian H. L. Hansen,Ez-Zoubir Amri,Lise Madsen,Lise Madsen,Giorgio Barbatelli,Bjørn Quistorff,Jacob B. Hansen +9 more
TLDR
It is demonstrated that forced expression of Tfam but not Tfb2m in brown adipocyte precursor cells promotes mitochondrial DNA replication, and that silencing of PRDM16 expression during brownfat cell differentiation blunts mitochondrial biogenesis and expression of brown fat cell markers.Abstract:
Background: Brown adipocytes are specialised in dissipating energy through adaptive thermogenesis, whereas white adipocytes are specialised in energy storage. These essentially opposite functions are possible for two reasons relating to mitochondria, namely expression of uncoupling protein 1 (UCP1) and a remarkably higher mitochondrial abundance in brown adipocytes. Methodology/Principal Findings: Here we report a comprehensive characterisation of gene expression linked to mitochondrial DNA replication, transcription and function during white and brown fat cell differentiation in vitro as well as in white and brown fat, brown adipose tissue fractions and in selected adipose tissues during cold exposure. We find a massive induction of the majority of such genes during brown adipocyte differentiation and recruitment, e.g. of the mitochondrial transcription factors A (Tfam) and B2 (Tfb2m), whereas only a subset of the same genes were induced during white adipose conversion. In addition, PR domain containing 16 (PRDM16) was found to be expressed at substantially higher levels in brown compared to white pre-adipocytes and adipocytes. We demonstrate that forced expression of Tfam but not Tfb2m in brown adipocyte precursor cells promotes mitochondrial DNA replication, and that silencing of PRDM16 expression during brown fat cell differentiation blunts mitochondrial biogenesis and expression of brown fat cell markers. Conclusions/Significance: Using both in vitro and in vivo model systems of white and brown fat cell differentiation, we report a detailed characterisation of gene expression linked to mitochondrial biogenesis and function. We find significant differences in differentiating white and brown adipocytes, which might explain the notable increase in mitochondrial content observed during brown adipose conversion. In addition, our data support a key role of PRDM16 in triggering brown adipocyte differentiation, including mitochondrial biogenesis and expression of UCP1.read more
Citations
More filters
Journal ArticleDOI
Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress.
TL;DR: It is demonstrated that Prdm16 is preferentially expressed by stem cells throughout the nervous and haematopoietic systems and is required for their maintenance, partly by modulating oxidative stress.
Journal ArticleDOI
Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism
Qin Hao,Rachita Yadav,Astrid L. Basse,Sidsel Petersen,Si Brask Sonne,Simon Rasmussen,Qianhua Zhu,Zhike Lu,Jun Wang,Karine Audouze,Ramneek Gupta,Lise Madsen,Karsten Kristiansen,Jacob B. Hansen +13 more
TL;DR: A model for the intermediary glucose metabolism in activated BAT is proposed and fluxes through glycolysis and the pentose phosphate pathway are induced, the latter providing reducing equivalents for de novo fatty acid synthesis and entry of glucose carbon into the tricarboxylic acid cycle is restricted by PDK2 and PDK4.
Journal ArticleDOI
Glucagon-Like Peptide-1 (GLP-1) Reduces Mortality and Improves Lung Function in a Model of Experimental Obstructive Lung Disease in Female Mice
Niels-Erik Viby,Niels-Erik Viby,Marie S. Isidor,Katrine B Buggeskov,Steen Seier Poulsen,Jacob B. Hansen,Hannelouise Kissow +6 more
TL;DR: Results show that GLP-1R agonists have potential therapeutic potential in the treatment of obstructive pulmonary diseases, such as chronic obstructive lung disease, by decreasing the severity of acute exacerbations.
Journal ArticleDOI
Pain Inhibition by Optogenetic Activation of Specific Anterior Cingulate Cortical Neurons
Ling Gu,Megan L. Uhelski,Sanjay Anand,Mario I. Romero-Ortega,Young Tae Kim,Perry N. Fuchs,Samarendra K. Mohanty +6 more
TL;DR: A dramatic reduction of pain behavior in transgenic mice is reported by optogenetic stimulation of the inhibitory neural circuitry of the anterior cingulate cortex expressing channelrhodopsin-2, which underscores the inhibition of the ACC as a clinical alternative in inhibiting chronic pain, and leads to a better understanding of the pain processing circuitry ofThe cingulated cortex.
Journal ArticleDOI
MCT1 and MCT4 Expression and Lactate Flux Activity Increase During White and Brown Adipogenesis and Impact Adipocyte Metabolism.
Charlotte Møller Petersen,Mette D. Nielsen,Elise S. Andersen,Astrid L. Basse,Marie S. Isidor,Lasse K. Markussen,B. Viuff,Ian Henry Lambert,Jacob B. Hansen,Stine F. Pedersen +9 more
TL;DR: It is suggested that upregulation of MCT1- and MCT4-mediated lactate flux capacity and NBCe1-mediated HCO3−/pH homeostasis are important for the physiological function of mature adipocytes.
References
More filters
Journal Article
Protein Measurement with the Folin Phenol Reagent
TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
Journal ArticleDOI
Brown Adipose Tissue: Function and Physiological Significance
Barbara Cannon,Jan Nedergaard +1 more
TL;DR: The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.
Journal ArticleDOI
Metabolism of isolated fat cells. i. effects of hormones on glucose metabolism and lipolysis.
Journal ArticleDOI
Identification and Importance of Brown Adipose Tissue in Adult Humans
AM Cypess,Sanaz Lehman,Gethin Williams,Ilan Tal,Dean Rodman,Allison B. Goldfine,FC Kuo,Edwin L. Palmer,Yu-Hua Tseng,Alessandro Doria,Gerald M. Kolodny,C R Kahn +11 more
TL;DR: Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of (18)F-FDG PET-CT.
The Metabolism of Isolated Fat Cells: I. Effects of Hormones on Glucose Metabolism and Lipolysis
TL;DR: This article marks the beginning of Rodbell's interest in cell receptors and related his discovery that fat cells could be isolated from other cells by treating them with preparations of collagenase, and also found that insulin could stimulate glucose uptake.