Genetic and functional characterization of clonally derived adult human brown adipocytes

Kosaku Shinoda, Ineke H N Luijten, Yutaka Hasegawa, Haemin Hong, Si B. Sonne, Miae Kim, Ruidan Xue, Maria Chondronikola, Aaron M. Cypess, Yu Hua Tseng, Jan Nedergaard, Labros S. Sidossis, Shingo Kajimura

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

Brown adipose tissue (BAT) acts in mammals as a natural defense system against hypothermia, and its activation to a state of increased energy expenditure is believed to protect against the development of obesity. Even though the existence of BAT in adult humans has been widely appreciated, its cellular origin and molecular identity remain elusive largely because of high cellular heterogeneity within various adipose tissue depots. To understand the nature of adult human brown adipocytes at single cell resolution, we isolated clonally derived adipocytes from stromal vascular fractions of adult human BAT from two individuals and globally analyzed their molecular signatures. We used RNA sequencing followed by unbiased genome-wide expression analyses and found that a population of uncoupling protein 1 (UCP1)-positive human adipocytes possessed molecular signatures resembling those of a recruitable form of thermogenic adipocytes (that is, beige adipocytes). In addition, we identified molecular markers that were highly enriched in UCP1-positive human adipocytes, a set that included potassium channel K3 (KCNK3) and mitochondrial tumor suppressor 1 (MTUS1). Further, we functionally characterized these two markers using a loss-of-function approach and found that KCNK3 and MTUS1 were required for beige adipocyte differentiation and thermogenic function. The results of this study present new opportunities for human BAT research, such as facilitating cell-based disease modeling and unbiased screens for thermogenic regulators.

Original languageEnglish (US)
Pages (from-to)389-394
Number of pages6
JournalNature Medicine
Volume21
Issue number4
DOIs
StatePublished - Apr 1 2015

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Brown Adipocytes
Brown Adipose Tissue
Tissue
Adipocytes
Tumors
Hypothermia
Mammals
Potassium Channels
RNA Sequence Analysis
Proteins
Energy Metabolism
Genes
Chemical activation
Blood Vessels
Adipose Tissue
RNA
Neoplasms
Obesity
Genome
Research

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Shinoda, K., Luijten, I. H. N., Hasegawa, Y., Hong, H., Sonne, S. B., Kim, M., ... Kajimura, S. (2015). Genetic and functional characterization of clonally derived adult human brown adipocytes. Nature Medicine, 21(4), 389-394. https://doi.org/10.1038/nm.3819

Genetic and functional characterization of clonally derived adult human brown adipocytes. / Shinoda, Kosaku; Luijten, Ineke H N; Hasegawa, Yutaka; Hong, Haemin; Sonne, Si B.; Kim, Miae; Xue, Ruidan; Chondronikola, Maria; Cypess, Aaron M.; Tseng, Yu Hua; Nedergaard, Jan; Sidossis, Labros S.; Kajimura, Shingo.

In: Nature Medicine, Vol. 21, No. 4, 01.04.2015, p. 389-394.

Research output: Contribution to journalArticle

Shinoda, K, Luijten, IHN, Hasegawa, Y, Hong, H, Sonne, SB, Kim, M, Xue, R, Chondronikola, M, Cypess, AM, Tseng, YH, Nedergaard, J, Sidossis, LS & Kajimura, S 2015, 'Genetic and functional characterization of clonally derived adult human brown adipocytes', Nature Medicine, vol. 21, no. 4, pp. 389-394. https://doi.org/10.1038/nm.3819
Shinoda K, Luijten IHN, Hasegawa Y, Hong H, Sonne SB, Kim M et al. Genetic and functional characterization of clonally derived adult human brown adipocytes. Nature Medicine. 2015 Apr 1;21(4):389-394. https://doi.org/10.1038/nm.3819
Shinoda, Kosaku ; Luijten, Ineke H N ; Hasegawa, Yutaka ; Hong, Haemin ; Sonne, Si B. ; Kim, Miae ; Xue, Ruidan ; Chondronikola, Maria ; Cypess, Aaron M. ; Tseng, Yu Hua ; Nedergaard, Jan ; Sidossis, Labros S. ; Kajimura, Shingo. / Genetic and functional characterization of clonally derived adult human brown adipocytes. In: Nature Medicine. 2015 ; Vol. 21, No. 4. pp. 389-394.
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