SF1-Specific AMPK alpha 1 Deletion Protects Against Diet-Induced Obesity

: Patricia Seoane-Collazo, Juan Roa, Eva Rial-Pensado, Laura Liñares-Pose, Daniel Beiroa, Francisco Ruíz-Pino, Tania López-González, Donald A. Morgan, José Ángel Pardavila, María Jesús Sánchez-Tapia, Noelia Martínez-Sánchez, Cristina Contreras, Miguel Fidalgo, Carlos Diéguez, Roberto Coppari, Kamal Rahmouni, Rubén Nogueiras, Manuel Tena-Sempere, Miguel López

: 2018

Diabetes

: DIABETES

: 67

: 11

: 2213

: 2226

: 14

: 0012-1797

: 1939-327X

DOI: https://doi.org/10.2337/db17-1538

AMPK is a cellular gauge that is activated under conditions of low energy, increasing energy production and reducing energy waste. Current evidence links hypothalamic AMPK with the central regulation of energy balance. However, it is unclear whether targeting hypothalamic AMPK has beneficial effects in obesity. Here, we show that genetic inhibition of AMPK in the ventromedial nucleus of the hypothalamus (VMH) protects against high-fat diet (HFD)-induced obesity by increasing brown adipose tissue (BAT) thermogenesis and subsequently energy expenditure. Notably, this effect depends upon the AMPK alpha 1 isoform in steroidogenic factor 1 (SF1) neurons of the VMH, since mice bearing selective ablation of AMPK alpha 1 in SF1 neurons display resistance to diet-induced obesity, increased BAT thermogenesis, browning of white adipose tissue, and improved glucose and lipid homeostasis. Overall, our findings point to hypothalamic AMPK in specific neuronal populations as a potential druggable target for the treatment of obesity and associated metabolic disorders.