Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes.
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 gamma agonist rosiglitazone promotes not only the expression of PGC-1alpha 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.
Petrovic
Natasa
N
Wenner-Gren Institute, The Arrhenius Laboratories, Stockholm University, SE-106 91 Stockholm, Sweden. natasa.petrovic@wgi.su.se
Walden
Tomas B
TB
Shabalina
Irina G
IG
Timmons
James A
JA
Cannon
Barbara
B
Nedergaard
Jan
J
D052437:Adipocytes, Brown / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D052438:Adipocytes, White / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004822:Epididymis / Q000166:cytology; D005786:Gene Expression Regulation; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D000077154:Rosiglitazone; D022722:Thermogenesis / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D000071256:Uncoupling Protein 1; D050994:Voltage-Dependent Anion Channels / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D007004:Hypoglycemic Agents; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D045162:Thiazolidinediones; D015534:Trans-Activators; D014157:Transcription Factors; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D050994:Voltage-Dependent Anion Channels; D000077154:Rosiglitazone