Seminar

New strategies for obesity treatment: targeting hypothalamic AMPK with exosomes

Prof. Miguel López Pérez

Current pharmacological therapies for treating obesity are scarce and of limited efficacy. Recent data have demonstrated that the genetic ablation or loss of function of AMPK?1 in SF1 neurons of VMH induces feeding-independent resistance to obesity. This action involves the sympathetic activation of BAT thermogenesis. Herein, we have developed a nanobiomedicine approach using neuronal-targeted exosomes to deliver a plasmid encoding an AMPK?1 dominant negative mutant (AMPK?1-DN) for targeting SF1 neurons following intravenous injections. SF1-AMPK?1-DN exosomes significantly decreased body weight in obese mice. Notably, this effect was feeding-independent but involved activation of the SNS and an increase in BAT thermogenesis. These results underscore the potential of this exosome-driven approach allowing hypothalamic AMPK specific neuronal-targeting, introducing a new strategy to manipulate body weight and eventually limit obesity expansion.