A Reservoir of Brown Adipocyte Progenitors in Human Skeletal Muscle
Mihaela Crisan,Louis Casteilla,Louis Casteilla,Lorenz Lehr,Mamen Carmona,Ariane Paoloni-Giacobino,Solomon Yap,Bin Sun,Bertrand Léger,Alison J. Logar,Luc Pénicaud,Patrick Schrauwen,David Cameron-Smith,Aaron P. Russell,Bruno Péault,Jean-Paul Giacobino +15 more
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TLDR
The existence in human skeletal muscle and the prospective isolation of progenitor cells with a high potential for UCP1 expression are shown for the first time and the discovery of this reservoir generates a new hope of treating obesity by acting on energy dissipation.Abstract:
Brown adipose tissue uncoupling protein-1 (UCP1) plays a major role in the control of energy balance in rodents. It has long been thought, however, that there is no physiologically relevant UCP1 expression in adult humans. In this study we show, using an original approach consisting of sorting cells from various tissues and differentiating them in an adipogenic medium, that a stationary population of skeletal muscle cells expressing the CD34 surface protein can differentiate in vitro into genuine brown adipocytes with a high level of UCP1 expression and uncoupled respiration. These cells can be expanded in culture, and their UCP1 mRNA expression is strongly increased by cell-permeating cAMP derivatives and a peroxisome-proliferator-activated receptor-gamma (PPARgamma) agonist. Furthermore, UCP1 mRNA was detected in the skeletal muscle of adult humans, and its expression was increased in vivo by PPARgamma agonist treatment. All the studies concerning UCP1 expression in adult humans have until now been focused on the white adipose tissue. Here we show for the first time the existence in human skeletal muscle and the prospective isolation of progenitor cells with a high potential for UCP1 expression. The discovery of this reservoir generates a new hope of treating obesity by acting on energy dissipation.read more
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Chronic Peroxisome Proliferator-activated Receptor γ (PPARγ) Activation of Epididymally Derived White Adipocyte Cultures Reveals a Population of Thermogenically Competent, UCP1-containing Adipocytes Molecularly Distinct from Classic Brown Adipocytes
Natasa Petrovic,Tomas B. Walden,Irina G. Shabalina,James A. Timmons,Barbara Cannon,Barbara Cannon,Jan Nedergaard +6 more
TL;DR: It is reported here that chronic treatment with the peroxisome proliferator-activated receptor γ agonist rosiglitazone promotes not only the expression of PGC-1α and mitochondriogenesis in these cells but also a norepinephrine-augmentable UCP1 gene expression in a significant subset of the cells, providing these cells with a genuine thermogenic capacity.
Journal ArticleDOI
Cellular Bioenergetics as a Target for Obesity Therapy
TL;DR: This article integrates significant recent advances in identifying the factors that control the development and function of brown fat and skeletal muscle and in techniques to measure brown fat in human adults in relation to classical understandings of cellular bioenergetics to explore the potential for developing novel anti-obesity therapies that target cellular energy expenditure.
Journal ArticleDOI
Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat
Tim J. Schulz,Tian Lian Huang,Thien T. Tran,Hongbin Zhang,Kristy L. Townsend,Jennifer L. Shadrach,Jennifer L. Shadrach,Massimiliano Cerletti,Lindsay E. McDougall,Nino Giorgadze,Tamara Tchkonia,Denis Schrier,Dean Falb,James L. Kirkland,Amy J. Wagers,Amy J. Wagers,Yu-Hua Tseng +16 more
TL;DR: A subpopulation of adipogenic progenitors residing in murine brown fat, white fat, and skeletal muscle is identified and a dynamic interplay between these progenitor cells and inductive signals that act in concert to specify brown adipocyte development is demonstrated.
Journal ArticleDOI
Human Brown Adipose Tissue
TL;DR: The BAT organ is unique in that it has evolved to safely dissipate large amounts of chemical energy, a quality that might be harnessed to help humans deal with a dangerously hypercaloric environment and still remain in good health as discussed by the authors.
Journal ArticleDOI
Mitochondrial dysfunction in obesity.
Juan C. Bournat,Chester W. Brown +1 more
TL;DR: The review highlights recent findings regarding the functions of mitochondria in adipocytes, providing an understanding of their central roles in regulating substrate metabolism, energy expenditure, disposal of reactive oxygen species, and in the pathophysiology of obesity and insulin resistance, as well as roles in the mechanisms that affect adipogenesis and mature adipocyte function.
References
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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
A perivascular origin for mesenchymal stem cells in multiple human organs
Mihaela Crisan,Solomon Yap,Louis Casteilla,Louis Casteilla,Chien Wen Chen,Mirko Corselli,Tea Soon Park,Gabriella Andriolo,Bin Sun,Bo Zheng,Li Zhang,Cyrille Norotte,Pang-ning Teng,Jeremy Traas,Rebecca C. Schugar,Bridget M. Deasy,Stephen F. Badylak,Hans-Jörg Bühring,Jean-Paul Giacobino,Lorenza Lazzari,Johnny Huard,Bruno Péault +21 more
TL;DR: Blood vessel walls harbor a reserve of progenitor cells that may be integral to the origin of the elusive MSCs and other related adult stem cells.
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Unexpected evidence for active brown adipose tissue in adult humans
TL;DR: It is concluded that a substantial fraction of adult humans possess active brown adipose tissue that thus has the potential to be of metabolic significance for normal human physiology as well as to become pharmaceutically activated in efforts to combat obesity.
Journal ArticleDOI
Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia
Christophe Fleury,Maria Neverova,Sheila Collins,Serge Raimbault,Odette Champigny,Corinne Levi-Meyrueis,Frédéric Bouillaud,Michael F. Seldin,Richard S. Surwit,Daniel Ricquier,Craig H Warden +10 more
TL;DR: The discovery of a gene that codes for a novel uncoupling protein, designated UCP2, which has 59% amino-acid identity to UCP1, is reported, and properties consistent with a role in diabetes and obesity are described, suggesting that U CP2 has a unique role in energy balance, body weight regulation and thermoregulation and their responses to inflammatory stimuli.