P21-activated kinase-1 signaling is required to preserve adipose tissue homeostasis and cardiac function.

Autor: Munoz M; Divison of Endocrinology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA., Solis C; Department of Health, Nutrition & Food Sciences, Florida State University, Tallahassee, FL, USA., McCann M; Department of Ophthalmology & Visual Sciences, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA., Park J; Department of Physiology & Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA., Rafael-Clyke K; Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA., Chowdhury SAK; Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA., Jiang Y; Department of Physiology & Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA., Rosas PC; Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA. prosas@uic.edu.
Jazyk: angličtina
Zdroj: Molecular and cellular biochemistry [Mol Cell Biochem] 2024 Mar 02. Date of Electronic Publication: 2024 Mar 02.
DOI: 10.1007/s11010-024-04968-4
Abstrakt: While P21-activated kinase-1 (PAK1) has been extensively studied in relation to cardiovascular health and glucose metabolism, its roles within adipose tissue and cardiometabolic diseases are less understood. In this study, we explored the effects of PAK1 deletion on energy balance, adipose tissue homeostasis, and cardiac function utilizing a whole-body PAK1 knockout (PAK1 -/- ) mouse model. Our findings revealed that body weight differences between PAK1 -/- and WT mice emerged at 9 weeks of age, with further increases observed at 12 weeks. Furthermore, PAK1 -/- mice displayed increased fat mass and decreased lean mass at 12 weeks, indicating a shift towards adiposity. In conjunction with the increased body weight, PAK1 -/- mice had increased food intake and reduced energy expenditure. At a mechanistic level, PAK1 deletion boosted the expression of lipogenic markers while diminishing thermogenic markers expression in adipose tissues, contributing to reduced energy expenditure and the overall obesogenic phenotype. Moreover, our findings highlighted a significant impact on cardiac function following PAK1 deletion, including alterations in calcium kinetics and compromised systolic and lusitropy functions. In summary, our study emphasizes the significant role of PAK1 in weight regulation and cardiac function, enriching our comprehension of heart health and metabolism. These findings could potentially facilitate the identification of novel therapeutic targets in cardiometabolic diseases.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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