Hurtado Carneiro, VerónicaJuan Arévalo, YolandaFlores, Cinthya N.Herrero De Dios, CarmenPérez García, AnaContreras Jiménez, CristinaLópez, MiguelÁlvarez, ElviraSanz Miguel, María Del Carmen2025-01-242025-01-242025-01-15Hurtado-Carneiro V, Juan-Arevalo Y, Flores CN, Herrero-De-Dios C, Perez-Garcia A, Contreras C, Lopez M, Alvarez E, Sanz C. Enhanced thermogenesis in PAS Kinase-deficient male mice. Biochem Pharmacol. 2025 Jan 15;233:116757. doi: 10.1016/j.bcp.2025.116757. Epub ahead of print. PMID: 39824466.0006-295210.1016/j.bcp.2025.116757https://hdl.handle.net/20.500.14352/116048PAS domain-containing serine/threonine-protein kinase (PASK) is a nutrient and energy sensor regulated by fasting/refeeding conditions in hypothalamic areas involved in controlling energy balance. In this sense, PASK plays a role in coordinating the activation/inactivation of AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) in response to fasting. PASK deficiency protects against the development of diet-induced obesity. This has prompted an investigation into the potential role of PASK on energy expenditure through thermogenesis in adipose tissue. Our results indicate that PASK-deficient male mice exhibited higher brown adipose tissue (BAT) thermogenic activity and heat production. The inhibition of PASK function induces the expression of Uncoupling Protein 1 (UCP1) and the adipogenic marker peroxisome proliferator-activated receptor gamma (PPARγ) in BAT. In addition, PASK deficiency promotes the expression of UCP1 and other browning markers such as PR/SET Domain 16 (PRDM16) in inguinal white adipose tissue (WAT). PASK-deficient mice record an enhanced thermogenic response, even under stimuli such as β-3adrenergic receptor agonist or cold. This evidence reveals PASK as a new mechanism modulating BAT thermogenesis.engjournal article1873-2968https://doi.org/10.1016/j.bcp.2025.11675739824466https://www.sciencedirect.com/science/article/pii/S000629522500019X?via%3Dihubhttps://pubmed.ncbi.nlm.nih.gov/39824466/restricted access576Metabolic sensorsObesityBrown Adipose TissueBeige Adipose TissueEnergy MetabolismCiencias BiomédicasBiología celular (Farmacia)Medicina2407 Biología Celular2411 Fisiología Humana2415 Biología Molecular