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Direct evidence of brown adipocytes in different fat depots in children.

Rockstroh D, Landgraf K, Wagner IV, Gesing J, Tauscher R, Lakowa N, Kiess W, Bühligen U, Wojan M, Till H, Blüher M, Körner A - PLoS ONE (2015)

Bottom Line: 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.In addition, we observed significantly increased PRDM16 and PAT2 expression in subcutaneous and visceral AT samples with high UCP1 expression in adults.The presence was not restricted to typical perirenal locations, but they were also interspersed within WAT of visceral and subcutaneous depots.

View Article: PubMed Central - PubMed

Affiliation: Center for Pediatric Research Leipzig, University Hospital for Children & Adolescents, Department of Women's and Child Health, University of Leipzig, Leipzig, Germany; Integrated Research and Treatment Center (IFB), University of Leipzig, Leipzig, Germany.

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.

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Expression of brown, beige and white adipocyte markers in adipose tissue samples of children and adults.A: UCP1 mRNA expression was significantly increased in UCP1histological+ samples compared to lean and obese children as well as adult UCP1histological- samples with the exception of a single outlier from an UCP1histological- subcutaneous sample (indicated as black box). B: PRDM16 was also increased in UCP1histological+ compared to all other UCP1histological- samples. C, D, E and F: mRNA expression of PAT2, P2RX5, ZIC1 and LHX8 were not different in UCP1histological+ samples, although, one UCP1histological+ and one UCP1histological- sample presented exceedingly high PAT2 expression values, marked with black squares. G,H and I: mRNA expression of the beige adipocyte markers TMEM26 and HOXC9 was not different in UCP1histological+ samples, although, two UCP1histological+ samples (from different donors) presented exceedingly high HOXC9 values, marked with black squares. These samples showed only islets of UCP1 positive adipocytes. TBX1 mRNA expression was slightly increased in UCP1histological- samples of lean children and obese adults compared to UCP1histological+ samples. J and K: The WAT marker LEP was significantly decreased in UCP1histological+ samples compared to UCP1histological- samples in contrast to ASC1, another white specific marker. L: ADIPOQ, a general marker for AT was not different between UCP1histological+ and UCP1histological- samples. Target gene expression was normalized to the mean of the three housekeeping genes: ACTB, TBP and HPRT1. Statistical significance was assessed by one-way ANOVA and post-hoc Dunnett’s test and was compared to UCP1histological+ samples and marked with *P<0.05; **P< 0.01; ***P<0.001.
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pone.0117841.g002: Expression of brown, beige and white adipocyte markers in adipose tissue samples of children and adults.A: UCP1 mRNA expression was significantly increased in UCP1histological+ samples compared to lean and obese children as well as adult UCP1histological- samples with the exception of a single outlier from an UCP1histological- subcutaneous sample (indicated as black box). B: PRDM16 was also increased in UCP1histological+ compared to all other UCP1histological- samples. C, D, E and F: mRNA expression of PAT2, P2RX5, ZIC1 and LHX8 were not different in UCP1histological+ samples, although, one UCP1histological+ and one UCP1histological- sample presented exceedingly high PAT2 expression values, marked with black squares. G,H and I: mRNA expression of the beige adipocyte markers TMEM26 and HOXC9 was not different in UCP1histological+ samples, although, two UCP1histological+ samples (from different donors) presented exceedingly high HOXC9 values, marked with black squares. These samples showed only islets of UCP1 positive adipocytes. TBX1 mRNA expression was slightly increased in UCP1histological- samples of lean children and obese adults compared to UCP1histological+ samples. J and K: The WAT marker LEP was significantly decreased in UCP1histological+ samples compared to UCP1histological- samples in contrast to ASC1, another white specific marker. L: ADIPOQ, a general marker for AT was not different between UCP1histological+ and UCP1histological- samples. Target gene expression was normalized to the mean of the three housekeeping genes: ACTB, TBP and HPRT1. Statistical significance was assessed by one-way ANOVA and post-hoc Dunnett’s test and was compared to UCP1histological+ samples and marked with *P<0.05; **P< 0.01; ***P<0.001.

Mentions: On mRNA level, UCP1histological+ samples showed a ≥200fold increased UCP1 expression compared to UCP1histological- samples, verifying these islets as brown-like adipocytes (Fig. 2A). Of note, one subcutaneous UCP1histological- sample from a hernia repair showed a strong UCP1 expression, which was comparable to the expression in UCP1histological+ samples (Fig. 2A, black square). UCP1histological+ samples primarily originated from lean children, although we detected brown-like adipocytes in a perirenal sample of a 4 month old overweight girl (BMI-SDS 1.8). In none of the 43 subcutaneous samples from obese children we detected evidence for brown-like adipocytes. Concerning the age distribution, 60% of children with brown-like adipocytes were older than one year (seven children aged 0–2 years, two children aged 3–5 years, one child aged 10 years) (Table 3).


Direct evidence of brown adipocytes in different fat depots in children.

Rockstroh D, Landgraf K, Wagner IV, Gesing J, Tauscher R, Lakowa N, Kiess W, Bühligen U, Wojan M, Till H, Blüher M, Körner A - PLoS ONE (2015)

Expression of brown, beige and white adipocyte markers in adipose tissue samples of children and adults.A: UCP1 mRNA expression was significantly increased in UCP1histological+ samples compared to lean and obese children as well as adult UCP1histological- samples with the exception of a single outlier from an UCP1histological- subcutaneous sample (indicated as black box). B: PRDM16 was also increased in UCP1histological+ compared to all other UCP1histological- samples. C, D, E and F: mRNA expression of PAT2, P2RX5, ZIC1 and LHX8 were not different in UCP1histological+ samples, although, one UCP1histological+ and one UCP1histological- sample presented exceedingly high PAT2 expression values, marked with black squares. G,H and I: mRNA expression of the beige adipocyte markers TMEM26 and HOXC9 was not different in UCP1histological+ samples, although, two UCP1histological+ samples (from different donors) presented exceedingly high HOXC9 values, marked with black squares. These samples showed only islets of UCP1 positive adipocytes. TBX1 mRNA expression was slightly increased in UCP1histological- samples of lean children and obese adults compared to UCP1histological+ samples. J and K: The WAT marker LEP was significantly decreased in UCP1histological+ samples compared to UCP1histological- samples in contrast to ASC1, another white specific marker. L: ADIPOQ, a general marker for AT was not different between UCP1histological+ and UCP1histological- samples. Target gene expression was normalized to the mean of the three housekeeping genes: ACTB, TBP and HPRT1. Statistical significance was assessed by one-way ANOVA and post-hoc Dunnett’s test and was compared to UCP1histological+ samples and marked with *P<0.05; **P< 0.01; ***P<0.001.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4338084&req=5

pone.0117841.g002: Expression of brown, beige and white adipocyte markers in adipose tissue samples of children and adults.A: UCP1 mRNA expression was significantly increased in UCP1histological+ samples compared to lean and obese children as well as adult UCP1histological- samples with the exception of a single outlier from an UCP1histological- subcutaneous sample (indicated as black box). B: PRDM16 was also increased in UCP1histological+ compared to all other UCP1histological- samples. C, D, E and F: mRNA expression of PAT2, P2RX5, ZIC1 and LHX8 were not different in UCP1histological+ samples, although, one UCP1histological+ and one UCP1histological- sample presented exceedingly high PAT2 expression values, marked with black squares. G,H and I: mRNA expression of the beige adipocyte markers TMEM26 and HOXC9 was not different in UCP1histological+ samples, although, two UCP1histological+ samples (from different donors) presented exceedingly high HOXC9 values, marked with black squares. These samples showed only islets of UCP1 positive adipocytes. TBX1 mRNA expression was slightly increased in UCP1histological- samples of lean children and obese adults compared to UCP1histological+ samples. J and K: The WAT marker LEP was significantly decreased in UCP1histological+ samples compared to UCP1histological- samples in contrast to ASC1, another white specific marker. L: ADIPOQ, a general marker for AT was not different between UCP1histological+ and UCP1histological- samples. Target gene expression was normalized to the mean of the three housekeeping genes: ACTB, TBP and HPRT1. Statistical significance was assessed by one-way ANOVA and post-hoc Dunnett’s test and was compared to UCP1histological+ samples and marked with *P<0.05; **P< 0.01; ***P<0.001.
Mentions: On mRNA level, UCP1histological+ samples showed a ≥200fold increased UCP1 expression compared to UCP1histological- samples, verifying these islets as brown-like adipocytes (Fig. 2A). Of note, one subcutaneous UCP1histological- sample from a hernia repair showed a strong UCP1 expression, which was comparable to the expression in UCP1histological+ samples (Fig. 2A, black square). UCP1histological+ samples primarily originated from lean children, although we detected brown-like adipocytes in a perirenal sample of a 4 month old overweight girl (BMI-SDS 1.8). In none of the 43 subcutaneous samples from obese children we detected evidence for brown-like adipocytes. Concerning the age distribution, 60% of children with brown-like adipocytes were older than one year (seven children aged 0–2 years, two children aged 3–5 years, one child aged 10 years) (Table 3).

Bottom Line: 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.In addition, we observed significantly increased PRDM16 and PAT2 expression in subcutaneous and visceral AT samples with high UCP1 expression in adults.The presence was not restricted to typical perirenal locations, but they were also interspersed within WAT of visceral and subcutaneous depots.

View Article: PubMed Central - PubMed

Affiliation: Center for Pediatric Research Leipzig, University Hospital for Children & Adolescents, Department of Women's and Child Health, University of Leipzig, Leipzig, Germany; Integrated Research and Treatment Center (IFB), University of Leipzig, Leipzig, Germany.

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.

Show MeSH
Related in: MedlinePlus