Enhanced thermogenesis in PAS Kinase-deficient male mice.

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY Biochemical pharmacology Pub Date : 2025-01-15 DOI:10.1016/j.bcp.2025.116757

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

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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.

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PAS激酶缺陷雄性小鼠产热能力增强。

含PAS结构域的丝氨酸/苏氨酸蛋白激酶（PASK）是一种营养和能量传感器，受下丘脑区域的禁食/再摄食条件调节，参与控制能量平衡。从这个意义上说，PASK在协调amp活化蛋白激酶（AMPK）的激活/失活和雷帕霉素（mTOR）的机制靶点中发挥作用。缺乏PASK可以防止饮食引起的肥胖。这促使人们对PASK通过脂肪组织产热作用对能量消耗的潜在作用进行研究。我们的研究结果表明，缺乏pask的雄性小鼠表现出更高的棕色脂肪组织（BAT）产热活性和产热。抑制PASK功能可诱导BAT中解偶联蛋白1 （UCP1）和脂肪生成标记物过氧化物酶体增殖物激活受体γ (PPARγ)的表达。此外，PASK缺乏促进UCP1和其他褐变标志物如PR/SET Domain 16 （PRDM16）在腹沟白色脂肪组织（WAT）中的表达。即使在β-3肾上腺素能受体激动剂或寒冷等刺激下，pask缺陷小鼠的产热反应也会增强。这表明PASK是调节BAT产热的新机制。

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来源期刊

Biochemical pharmacology 医学-药学

CiteScore

10.30

自引率

1.70%

发文量

420

审稿时长

17 days

期刊介绍： Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.