Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice
Authors
Min, So YunKady, Jamie
Nam, Minwoo
Rojas-Rodriguez, Raziel
Berkenwald, Aaron
Kim, Jong Hun
Noh, Hye Lim
Kim, Jason K.
Cooper, Marcus P.
Fitzgibbons, Timothy P.
Brehm, Michael A.
Corvera, Silvia
UMass Chan Affiliations
UMass Metabolic NetworkDepartment of Medicine, Division of Cardiovascular Medicine
School of Medicine, Clinical Translational Research Pathway
Cardiovascular Center of Excellence
Diabetes Center of Excellence
Graduate School of Biomedical Sciences
Program in Molecular Medicine
Document Type
Journal ArticlePublication Date
2016-03-01Keywords
BiochemistryCell Biology
Cellular and Molecular Physiology
Developmental Biology
Molecular Biology
Metadata
Show full item recordAbstract
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.Source
Nat Med. 2016 Mar;22(3):312-8. doi: 10.1038/nm.4031. Epub 2016 Jan 25. Link to article on publisher's siteDOI
10.1038/nm.4031Permanent Link to this Item
http://hdl.handle.net/20.500.14038/44457PubMed ID
26808348Notes
So Yun Min, Minwoo Nam and Raziel Rojas-Rodriguez are students in the Graduate School of Biomedical Sciences at UMass Medical School.
Aaron Berkenwald is a medical student in the Clinical Translational Research Pathway at UMass Medical School.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/nm.4031