Enhanced thermogenesis in PAS Kinase-deficient male mice

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.