Hypothalamic AMPK and energy balance

Abstract

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.

Keywords: AMP-activated protein kinase; brown adipose tissue; food intake; hypothalamus; obesity.

Figure 1

Hypothalamic AMPK is a canonical regulator of energy balance. AMP‐activated protein kinase (AMPK) acts in the hypothalamus to modulate whole‐body energy homoeostasis and body weight. AMPK senses several nutritional and hormonal stimuli to regulate food intake, peripheral metabolism, brown adipose tissue (BAT) thermogenesis, and browning of white adipose tissue (WAT). The actions of hypothalamic AMPK on peripheral tissues/organs, such as BAT, WAT and liver, are mediated by specific regulation of the sympathetic (SNS) and parasympathetic nervous systems (PSNS), respectively. 3V: third ventricle; ARC: arcuate nucleus of the hypothalamus; PVH: paraventricular nucleus of the hypothalamus; VMH: ventromedial nucleus of the hypothalamus