A Reservoir of Brown Adipocyte Progenitors in Human Skeletal Muscle

Author:

Crisan Mihaela12,Casteilla Louis32,Lehr Lorenz4,Carmona Mamen3,Paoloni-Giacobino Ariane5,Yap Solomon2,Sun Bin2,Léger Bertrand6,Logar Alison2,Pénicaud Luc3,Schrauwen Patrick7,Cameron-Smith David8,Russell Aaron Paul8,Péault Bruno12,Giacobino Jean-Paul2

Affiliation:

1. McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

2. Stem Cell Research Center, Children's Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

3. UMR 5241 CNRS-UPS, IFR 31, Institut Louis Bugnard, Toulouse, France

4. Department of Cell Physiology and Metabolism, Centre Médical Universitaire, University of Geneva, Geneva, Switzerland

5. Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

6. Clinique Romande de Réadaptation, SUVA Care, Sion, Switzerland

7. Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

8. School of Exercise and Nutrition Sciences, Deakin University, Burwood, Australia

Abstract

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

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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