Antiobesity Strategy Targets Energy Economy Safeguards

Abstract

A fundamental barrier in obesity management is that caloric restriction triggers energy-conserving responses that evolved to prevent body weight loss. ATP-sensitive potassium (KATP) channels have been identified as safeguards controlling energy expenditure in skeletal muscles and thereby key factors determining body weight.1 In this issue of Molecular Therapy, Koganti and colleagues report the successful reduction of muscle energy efficiency through targeted intramuscular injections of cell-penetrating vivo-morpholinos to prevent translation of the channel pore-forming Kir6.2 subunit.2 In this elegant proof-of-concept study, the authors demonstrate localized reduction of KATP channel expression and function, leading in turn to an increase in activity-related energy consumption, without compromising exercise tolerance. This report opens a new avenue of investigation in targeted therapies aiming to control weight management.