Enhanced thermogenesis in PAS Kinase-deficient male mice

Veronica Hurtado-Carneiro; Yolanda Juan-Arevalo; Cinthya N Flores; Carmen Herrero-De-Dios; Ana Perez-García; Cristina Contreras; Miguel Lopez; Elvira Alvarez; Carmen Sanz

doi:10.1016/j.bcp.2025.116757

Enhanced thermogenesis in PAS Kinase-deficient male mice

Biochem Pharmacol. 2025 Jan 15:116757. doi: 10.1016/j.bcp.2025.116757. Online ahead of print.

Authors

Veronica Hurtado-Carneiro¹, Yolanda Juan-Arevalo², Cinthya N Flores², Carmen Herrero-De-Dios³, Ana Perez-García³, Cristina Contreras⁴, Miguel Lopez⁵, Elvira Alvarez⁶, Carmen Sanz⁷

Affiliations

¹ Department of Physiology, Faculty of Medicine, Complutense University of Madrid, Spain; Institute of Medical Research at the San Carlos Clinic Hospital (IdISSC), Madrid, Spain. Electronic address: [email protected].
² Department of Physiology, Faculty of Medicine, Complutense University of Madrid, Spain; Department of Cell Biology, Faculty of Medicine, Complutense University of Madrid, Spain.
³ Department of Cell Biology, Faculty of Medicine, Complutense University of Madrid, Spain.
⁴ Department of Physiology, Faculty of Pharmacy, Complutense University of Madrid, Spain; NeurObesity Group, Department of Physiology, CiMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.
⁵ NeurObesity Group, Department of Physiology, CiMUS, University of Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
⁶ Institute of Medical Research at the San Carlos Clinic Hospital (IdISSC), Madrid, Spain.
⁷ Department of Cell Biology, Faculty of Medicine, Complutense University of Madrid, Spain; Institute of Medical Research at the San Carlos Clinic Hospital (IdISSC), Madrid, Spain.

PMID: 39824466
DOI: 10.1016/j.bcp.2025.116757

Abstract

PAS 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.

Keywords: Beige Adipose Tissue; Brown Adipose Tissue; Energy Metabolism; Metabolic sensors; Obesity.