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. 2021 Oct;3(10):1288-1289.
doi: 10.1038/s42255-021-00463-y.

A blood-to-brain delivery system to treat obesity

Clarissa M D Mota  1 , Christopher J Madden  2
Affiliations

A blood-to-brain delivery system to treat obesity

Clarissa M D Mota et al. Nat Metab. 2021 Oct.

Abstract

Small extracellular vesicles (SEVs) can be used for the selective delivery of therapeutic agents to the brain. Milbank et al. make use of a blood-to-brain delivery system by using SEVs for selectively targeting neurons in the ventromedial hypothalamus (VMH) of mice, extending this exciting approach to potential applications for the treatment of obesity.

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Conflict of interest statement

Conflict of interest: The authors declare that they have no conflicts of interest with the contents of this article.

Figures

Figure 1.
Figure 1.. Peripherally-administered SEVs reach the VMH and trigger sympathetic outflow that leads to body weight loss.
Systemically-administered small extracellular vesicles (SEVs) carrying plasmids encoding an AMP-activated protein kinase α1 (AMPKα1), dominant negative mutant (DN) under the control of the steroidogenic factor 1 (SF-1) promoter preferentially target SF-1-expressing neurons in the ventromedial hypothalamus (VMH) to decrease the activity of AMPKα1 in these cells. The inhibition of AMPKα1 in SF-1-expressing neurons activates undefined brain pathways that increase the sympathetic outflow to brown adipose tissue (BAT), and thereby drive lipid-consuming thermogenesis in BAT, resulting in a decrease in white adipose tissue (WAT). In the absence of a concomitant increase in food intake the increased sympathetically-mediated metabolism in adipose tissue results in weight loss.
See this image and copyright information in PMC

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