Human beige adipocyte precursors associated with capillary networks proliferate in response to angiocrines, and when activated in vitro and transplanted into mice, they improve glucose intolerance. 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 depots1,2,3,4, 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 phenotype5,6,7,8, 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 IL2rgnull (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.

Altered energy balance and insulin resistance are important characteristics of aging. Skeletal muscle is a major site of glucose disposal, and the role of aging‐associated inflammation in skeletal muscle insulin resistance remains unclear. To investigate, we examined glucose metabolism in 18‐mo‐old transgenic mice with muscle‐specific overexpression of IL‐10 (M ^IL10 ) and in wild‐type mice during hyperinsulinemic‐euglycemic clamping. Despite similar fat mass and energy balance, M ^IL10 mice were protected from aging‐associated insulin resistance with significant increases in glucose infusion rates, whole‐body glucose turnover, and skeletal muscle glucose uptake (~60%; P <0.05), as compared to age‐matched WT mice. This protective effect was associated with decreased muscle inflammation, but no changes in adipose tissue inflammation in aging M ^IL10 mice. These results demonstrate the importance of skeletal muscle inflammation in aging‐mediated insulin resistance, and our findings further implicate a potential therapeutic role of anti‐inflammatory cytokine in the treatment of aging‐mediated insulin resistance.—Dagdeviren, S., Jung, D. Y., Friedline, R. H., Noh, H. L., Kim, J. H., Patel, P. R., Tsitsilianos, N., Inashima, K., Tran, D. A., Hu, X., Loubato, M. M., Craige, S. M., Kwon, J. Y., Lee, K. W., Kim, J. K. IL‐10 prevents aging‐associated inflammation and insulin resistance in skeletal muscle. FASEB J. 31, 701–710 (2017). http://www.fasebj.org

Insulin resistance is a major characteristic of obesity and type 2 diabetes, but the underlying mechanism is unclear. Recent studies have shown a metabolic role of capsaicin that may be mediated via ...