SF1-Specific AMPKα1 Deletion Protects Against Diet-Induced Obesity.
Patricia Seoane-CollazoJuan RoaEva Rial-PensadoLaura Liñares-PoseDaniel BeiroaFrancisco Ruíz-PinoTania López-GonzálezDonald A MorganJosé Ángel PardavilaMaría Jesús Sánchez-TapiaNoelia Martínez-SánchezCristina ContrerasMiguel FidalgoCarlos DiéguezRoberto CoppariKamal RahmouniRubén NogueirasManuel Tena-SempereMiguel LópezPublished in: Diabetes (2018)
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 AMPKα1 isoform in steroidogenic factor 1 (SF1) neurons of the VMH, since mice bearing selective ablation of AMPKα1 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.
Keyphrases
- insulin resistance
- adipose tissue
- high fat diet
- skeletal muscle
- high fat diet induced
- metabolic syndrome
- weight loss
- type diabetes
- protein kinase
- weight gain
- spinal cord
- drug delivery
- blood pressure
- risk assessment
- climate change
- endothelial cells
- ultrasound guided
- genome wide
- heavy metals
- oxidative stress
- blood glucose
- body mass index
- cancer therapy
- fatty acid
- drug induced
- spinal cord injury
- stress induced
- radiofrequency ablation