Activation of brown adipose tissue (BAT) to increase energy expenditure is an attractive anti-obesity strategy, but attempts so far have been limited by side-effects. Here, Wang et al. engineer human white pre-adipocytes using CRISPR–Cas9 to activate expression of uncoupling protein 1, thereby creating human brown-like (HUMBLE) cells. Transplantation of HUMBLE cells into diet-induced obese mouse models improved glucose tolerance and insulin sensitivity, increased energy expenditure and reduced weight gain, without side-effects. The HUMBLE cells activated endogenous BAT, through increased production and red blood cell-mediated delivery of nitric oxide.
Nature Reviews Drug Discovery 19, 672 (2020)