Human BAT possesses molecular signatures that resemble beige/brite cells

PLoS One. 2012;7(11):e49452. doi: 10.1371/journal.pone.0049452. Epub 2012 Nov 16.

Abstract

Brown adipose tissue (BAT) dissipates chemical energy and generates heat to protect animals from cold and obesity. Rodents possess two types of UCP-1 positive brown adipocytes arising from distinct developmental lineages: "classical" brown adipocytes develop during the prenatal stage whereas "beige" or "brite" cells that reside in white adipose tissue (WAT) develop during the postnatal stage in response to chronic cold or PPARγ agonists. Beige cells' inducible characteristics make them a promising therapeutic target for obesity treatment, however, the relevance of this cell type in humans remains unknown. In the present study, we determined the gene signatures that were unique to classical brown adipocytes and to beige cells induced by a specific PPARγ agonist rosiglitazone in mice. Subsequently we applied the transcriptional data to humans and examined the molecular signatures of human BAT isolated from multiple adipose depots. To our surprise, nearly all the human BAT abundantly expressed beige cell-selective genes, but the expression of classical brown fat-selective genes were nearly undetectable. Interestingly, expression of known brown fat-selective genes such as PRDM16 was strongly correlated with that of the newly identified beige cell-selective genes, but not with that of classical brown fat-selective genes. Furthermore, histological analyses showed that a new beige cell marker, CITED1, was selectively expressed in the UCP1-positive beige cells as well as in human BAT. These data indicate that human BAT may be primary composed of beige/brite cells.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / cytology*
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / cytology
  • Animals
  • DNA-Binding Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Ion Channels / metabolism*
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Inbred C57BL
  • Microarray Analysis
  • Mitochondrial Proteins / metabolism*
  • Myogenic Regulatory Factor 5 / metabolism
  • Nuclear Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • PPAR gamma / agonists
  • Rosiglitazone
  • Thiazolidinediones
  • Transcription Factors / metabolism
  • Uncoupling Protein 1

Substances

  • CITED1 protein, human
  • DNA-Binding Proteins
  • Ion Channels
  • MYF5 protein, human
  • Mitochondrial Proteins
  • Myogenic Regulatory Factor 5
  • Nuclear Proteins
  • PPAR gamma
  • PRDM16 protein, human
  • Thiazolidinediones
  • Transcription Factors
  • UCP1 protein, human
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Rosiglitazone