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Nat Med. 2016 Mar;22(3):312-8. doi: 10.1038/nm.4031. Epub 2016 Jan 25.

Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice.

Author information

1
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
2
Graduate School of Biomedical Sciences, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
3
Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
4
Cardiovascular Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
5
Clinical Translational Research Pathway, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

Abstract

Uncoupling protein 1 (UCP1) is highly expressed in brown adipose tissue, where it generates heat by uncoupling electron transport from ATP production. UCP1 is also found outside classical brown adipose tissue depots, in adipocytes that are termed 'brite' (brown-in-white) or 'beige'. In humans, the presence of brite or beige (brite/beige) adipocytes is correlated with a lean, metabolically healthy phenotype, but whether a causal relationship exists is not clear. Here we report that human brite/beige adipocyte progenitors proliferate in response to pro-angiogenic factors, in association with expanding capillary networks. Adipocytes formed from these progenitors transform in response to adenylate cyclase activation from being UCP1 negative to being UCP1 positive, which is a defining feature of the beige/brite phenotype, while displaying uncoupled respiration. When implanted into normal chow-fed, or into high-fat diet (HFD)-fed, glucose-intolerant NOD-scid IL2rg(null) (NSG) mice, brite/beige adipocytes activated in vitro enhance systemic glucose tolerance. These adipocytes express neuroendocrine and secreted factors, including the pro-protein convertase PCSK1, which is strongly associated with human obesity. Pro-angiogenic conditions therefore drive the proliferation of human beige/brite adipocyte progenitors, and activated beige/brite adipocytes can affect systemic glucose homeostasis, potentially through a neuroendocrine mechanism.

PMID:
26808348
PMCID:
PMC4777633
DOI:
10.1038/nm.4031
[Indexed for MEDLINE]
Free PMC Article

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