Direct evidence of brown adipocytes in different fat depots in children

PLoS One. 2015 Feb 23;10(2):e0117841. doi: 10.1371/journal.pone.0117841. eCollection 2015.

Abstract

Recent studies suggested the persistence of brown adipocytes in adult humans, as opposed to being exclusively present in infancy. In this study, we investigated the presence of brown-like adipocytes in adipose tissue (AT) samples of children and adolescents aged 0 to 18 years and evaluated the association with age, location, and obesity. For this, we analysed AT samples from 131 children and 23 adults by histological, immunohistochemical and expression analyses. We detected brown-like and UCP1 positive adipocytes in 10.3% of 87 lean children (aged 0.3 to 10.7 years) and in one overweight infant, whereas we did not find brown adipocytes in obese children or adults. In our samples, the brown-like adipocytes were interspersed within white AT of perirenal, visceral and also subcutaneous depots. Samples with brown-like adipocytes showed an increased expression of UCP1 (>200fold), PRDM16 (2.8fold), PGC1α and CIDEA while other brown/beige selective markers, such as PAT2, P2RX5, ZIC1, LHX8, TMEM26, HOXC9 and TBX1 were not significantly different between UCP1 positive and negative samples. We identified a positive correlation between UCP1 and PRDM16 within UCP1 positive samples, but not with any other brown/beige marker. In addition, we observed significantly increased PRDM16 and PAT2 expression in subcutaneous and visceral AT samples with high UCP1 expression in adults. Our data indicate that brown-like adipocytes are present well beyond infancy in subcutaneous depots of non-obese children. The presence was not restricted to typical perirenal locations, but they were also interspersed within WAT of visceral and subcutaneous depots.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / metabolism
  • Adipocytes, Brown / cytology*
  • Adipocytes, Brown / metabolism
  • Adipose Tissue, Brown / cytology*
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White / cytology*
  • Adipose Tissue, White / metabolism
  • Adolescent
  • Adult
  • Amino Acid Transport Systems, Neutral / genetics
  • Amino Acid Transport Systems, Neutral / metabolism
  • Body Mass Index
  • Child
  • Child, Preschool
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Infant
  • Infant, Newborn
  • Intra-Abdominal Fat / cytology
  • Intra-Abdominal Fat / metabolism
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Male
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Obesity
  • Overweight
  • Reverse Transcriptase Polymerase Chain Reaction
  • Subcutaneous Fat / cytology
  • Subcutaneous Fat / metabolism
  • Symporters / genetics
  • Symporters / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Uncoupling Protein 1

Substances

  • Amino Acid Transport Systems, Neutral
  • DNA-Binding Proteins
  • Ion Channels
  • Mitochondrial Proteins
  • PRDM16 protein, human
  • SLC36A2 protein, human
  • Symporters
  • Transcription Factors
  • UCP1 protein, human
  • Uncoupling Protein 1

Grants and funding

This work was supported by grants from the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001 (IFB AdiposityDiseases), the German Research Council (DFG) for the Clinical Research Center “Obesity Mechanisms” CRC1052/1 C05 and the European Community’s 7th Framework Programme (FP7/2007–2013) project Beta-JUDO under grant agreement n° 279153 to A.K. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.