Hypothalamic AMPK and energy balance

AMP-activated protein kinase (AMPK) is the main cellular energy sensor. Activated following a depletion of cellular energy stores, AMPK will restore the energy homoeostasis by increasing energy production and limiting energy waste. At a central level, the AMPK pathway will integrate peripheral signals (mostly hormones and metabolites) through neuronal networks. Hypothalamic AMPK is directly implicated in feeding behaviour, brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT). It also participates in other metabolic functions: glucose and muscle metabolisms, as well as hepatic function. Numerous anti-obesity and/or antidiabetic agents, such as nicotine, metformin and liraglutide, are known to induce their effects through a modulation of AMPK pathway, either at central or at peripheral levels. Moreover, the weight-gaining side effects of antipsychotic drugs, such as olanzapine, are also mediated by hypothalamic AMPK. Therefore, considering hypothalamic AMPK as a therapeutic target in metabolic diseases appears as an interesting strategy due to its implication in feeding and energy expenditure, the two sides of the energy balance equation.