Comprehensive molecular characterization of human adipocytes reveals a transient brown phenotype.
BACKGROUND
Functional brown adipose tissue (BAT), involved in energy expenditure, has recently been detected in substantial amounts in adults. Formerly overlooked BAT has now become an attractive anti-obesity target.


RESULTS
Molecular characterization of human brown and white adipocytes, using a myriad of techniques including high-throughput RNA sequencing and functional assays, showed that PAZ6 and SW872 cells exhibit classical molecular and phenotypic markers of brown and white adipocytes, respectively. However, the pre-adipocyte cell line SGBS presents a versatile phenotype. A transit expression of classical brown markers such as UCP1 and PPARγ peaked and declined at day 28 post-differentiation initiation. Conversely, white adipocyte markers, including Tcf21, showed reciprocal behavior. Interestingly, leptin levels peaked at day 28 whereas the highest adiponectin mRNA levels were detected at day 14 of differentiation. Phenotypic analysis of the abundance and shape of lipid droplets were consistent with the molecular patterns. Accordingly, the oxidative capacity of SGBS adipocytes peaked on differentiation day 14 and declined progressively towards differentiation day 28.


CONCLUSIONS
Our studies have unveiled a new phenotype of human adipocytes, providing a tool to identify molecular gene expression patterns and pathways involved in the conversion between white and brown adipocytes.
Laboratory of Genetic Medicine & Immunology, Weill Cornell Medical College in Qatar, P.O. Box 24144, Doha, Qatar. anw2028@qatar-med.cornell.edu.
Andrea
A
Guennoun
Center for Diabetes and Metabolic Diseases, The Scripps Research Institute, Florida, USA. MKazantz@scripps.edu.
Melissa
M
Kazantzis
Laboratory of Genetic Medicine & Immunology, Weill Cornell Medical College in Qatar, P.O. Box 24144, Doha, Qatar. ret2007@qatar-med.cornell.edu.
Remy
R
Thomas
Department of Paediatrics and Adolescent Medicine, Division of Pediatric Endocrinology and Diabetology, Ulm, Germany. Martin.Wabitsch@uniklinik-ulm.de.
Martin
M
Wabitsch
Department of Paediatrics and Adolescent Medicine, Division of Pediatric Endocrinology and Diabetology, Ulm, Germany. Daniel.Tews@uniklinik-ulm.de.
Daniel
D
Tews
Laboratory of Genetic Medicine & Immunology, Weill Cornell Medical College in Qatar, P.O. Box 24144, Doha, Qatar. kss2005@qatar-med.cornell.edu.
Konduru
K
Seetharama Sastry
Department of Physiology, King Saud University, Riyadh, Saudi Arabia. mouaadh.abdelkarim@gmail.com.
Mouaadh
M
Abdelkarim
Institut Cochin INSERM U1016, Université Paris 7-Denis-Diderot, Paris, France. tarik.issad@inserm.fr.
Vladimir
V
Zilberfarb
Department of Infectology, The Scripps Research Institute-Florida, Jupiter, FL, USA. strosber@scripps.edu.
Arthur Donny
AD
Strosberg
Laboratory of Genetic Medicine & Immunology, Weill Cornell Medical College in Qatar, P.O. Box 24144, Doha, Qatar. loc2008@qatar-med.cornell.edu.
Lotfi
L
Chouchane
D017667:Adipocytes / Q000166:cytology; D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism*; D052438:Adipocytes, White / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis; D052242:Adiponectin / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D017423:Sequence Analysis, RNA; D000071256:Uncoupling Protein 1
D052242:Adiponectin; D018076:DNA, Complementary; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; D042967:Electron Transport Complex I; D010100:Oxygen