RT Journal Article
T1 PAS Kinase Is a Nutrient and Energy Sensor in Hypothalamic Areas Required for the Normal Function of AMPK and mTOR/S6K1
A1 Hurtado Carneiro, Verónica
A1 Roncero Rincón, Isabel
A1 Egger, Sascha
A1 Wenger, Roland
A1 Blázquez Fernández, Enrique
A1 Sanz Miguel, María Del Carmen
A1 Álvarez García, Elvira
A2 Bazán, Nicolas
AB The complications caused by overweight, obesity and type 2 diabetes are one of the main problems that increase morbidity and mortality in developed countries. Hypothalamic metabolic sensors play an important role in the control of feeding and energy homeostasis. PAS kinase (PASK) is a nutrient sensor proposed as a regulator of glucose metabolism and cellular energy. The role of PASK might be similar to other known metabolic sensors, such as AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR). PASK-deficient mice resist diet-induced obesity. We have recently reported that AMPK and mTOR/S6K1 pathways are regulated in the ventromedial and lateral hypothalamus in response to nutritional states, being modulated by anorexigenic glucagon-like peptide-1 (GLP-1)/exendin-4 in lean and obese rats. We identified PASK in hypothalamic areas, and its expression was regulated under fasting/re-feeding conditions and modulated by exendin-4. Furthermore, PASK-deficient mice have an impaired activation response of AMPK and mTOR/S6K1 pathways. Thus, hypothalamic AMPK and S6K1 were highly activated under fasted/re-fed conditions. Additionally, in this study, we have observed that the exendin-4 regulatory effect in the activity of metabolic sensors was lost in PASK-deficient mice, and the anorexigenic properties of exendin-4 were significantly reduced, suggesting that PASK could be a mediator in the GLP-1 signalling pathway. Our data indicated that the PASK function could be critical for preserving the nutrient effect on AMPK and mTOR/S6K1 pathways and maintain the regulatory role of exendin-4 in food intake. Some of the antidiabetogenic effects of exendin-4 might be modulated through these processes.
PB Springer Link
SN 0893-7648
YR 2014
FD 2014
LK https://hdl.handle.net/20.500.14352/94938
UL https://hdl.handle.net/20.500.14352/94938
LA eng
NO Hurtado-Carneiro, V., Roncero, I., Egger, S.S. et al. PAS Kinase Is a Nutrient and Energy Sensor in Hypothalamic Areas Required for the Normal Function of AMPK and mTOR/S6K1. Mol Neurobiol 50, 314–326 (2014). https://doi.org/10.1007/s12035-013-8630-4
NO Ministerio de Ciencia e Innovación (España)
NO Universidad Complutense de Madrid
NO Instituto de Salud Carlos III
NO Banco Santander
NO Fundación Mutua Madrileña
NO Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas
DS Docta Complutense
RD 6 abr 2025