Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice
Program in Molecular Medicine; Graduate School of Biomedical Sciences; Diabetes Center of Excellence; Cardiovascular Center of Excellence; School of Medicine, Clinical Translational Research Pathway; Department of Medicine, Division of Cardiovascular Medicine; UMass Metabolic Network
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Developmental Biology | Molecular Biology
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.
DOI of Published Version
Nat Med. 2016 Mar;22(3):312-8. doi: 10.1038/nm.4031. Epub 2016 Jan 25. Link to article on publisher's site
Min, So Yun; Kady, 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.; and Corvera, Silvia, "Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice" (2016). Program in Molecular Medicine Publications and Presentations. 51.