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TISSUE-SPECIFIC STEM CELLS

A Reservoir of Brown Adipocyte Progenitors in Human Skeletal Muscle

^aStem Cell Research Center, Children's Hospital,
^bMcGowan Institute for Regenerative Medicine, and
^eDepartment of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;
^cUMR 5241 CNRS-UPS, IFR 31, Institut Louis Bugnard, Toulouse, France;
^dDepartment of Cell Physiology and Metabolism, Centre Médical Universitaire, University of Geneva, Geneva, Switzerland;
^fClinique Romande de Réadaptation, SUVA Care, Sion, Switzerland;
^gDepartment of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands;
^hSchool of Exercise and Nutrition Sciences, Deakin University, Burwood, Australia

Key Words. Brown adipocytes • Human muscle

Correspondence: Correspondence: Jean-Paul Giacobino, M.D., 16 rue Jean-Sénebier, 1205 Geneva, Switzerland. Telephone: 4122-310-62-84; Fax: 4122-379-52-28; e-mail: jean-paul.giacobino{at}medecine.unige.ch

Received on April 3, 2008; accepted for publication on June 25, 2008.

First published online in STEM CELLS EXPRESS  July 10, 2008.

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- (PPAR) agonist. Furthermore, UCP1 mRNA was detected in the skeletal muscle of adult humans, and its expression was increased in vivo by PPAR 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.

Disclosure of potential conflicts of interest is found at the end of this article.

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