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

• Published in: The Journal of biological chemistry 2010-03, Vol.285 (10), p.7153-7164
• Main Authors: Petrovic, Natasa, Walden, Tomas B., Shabalina, Irina G., Timmons, James A., Cannon, Barbara, Nedergaard, Jan
• Format: Article
• Language: English
• Subjects: Adipocytes, Brown - cytology; Adipocytes, Brown - drug effects; Adipocytes, Brown - physiology; Adipocytes, White - cytology; Adipocytes, White - drug effects; Adipocytes, White - physiology; Animals; Biomarkers - metabolism; Brown Adipocytes; Cell Biology; Cell Differentiation - physiology; Cells, Cultured; Coculture Techniques; Development Differentiation/Adipocyte; Epididymis - cytology; Gene Expression Regulation; Hypoglycemic Agents - pharmacology; Ion Channels - genetics; Ion Channels - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopic Imaging; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Mouse; Oxygen Consumption - physiology; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; PPAR gamma - agonists; PPAR gamma - genetics; PPAR gamma - metabolism; PPARγ; Receptors/Nuclear; Rosiglitazone; Subcellular Organelles/Mitochondria; Thermogenesis - physiology; Thiazolidinediones - pharmacology; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factors; UCP1; Uncoupling Protein 1; Voltage-Dependent Anion Channels - genetics; Voltage-Dependent Anion Channels - metabolism; White Adipocytes
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.053942

The recent insight that brown adipocytes and muscle cells share a common origin and in this respect are distinct from white adipocytes has spurred questions concerning the origin and molecular characteristics of the UCP1-expressing cells observed in classic white adipose tissue depots under certain physiological or pharmacological conditions. Examining precursors from the purest white adipose tissue depot (epididymal), we report 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. However, although functional thermogenic genes are expressed, the cells are devoid of transcripts for the novel transcription factors now associated with classic brown adipocytes (Zic1, Lhx8, Meox2, and characteristically PRDM16) or for myocyte-associated genes (myogenin and myomirs (muscle-specific microRNAs)) and retain white fat characteristics such as Hoxc9 expression. Co-culture experiments verify that the UCP1-expressing cells are not proliferating classic brown adipocytes (adipomyocytes), and these cells therefore constitute a subset of adipocytes (“brite” adipocytes) with a developmental origin and molecular characteristics distinguishing them as a separate class of cells.