Thepharmacological activation of AMPK as a treatment strategyfor obesity and type-II diabetes was first proposed in the 1990s andled to the development of a diverse range of AMPK activators withdifferent modes of action.2 The followingsection will describe several small molecule AMPK activators categorizedby their type of action (indirect/direct) or site of action. This evidence concerns the gene PRKAA2 and obesity due to melanocortin 4 receptor deficiency.