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Rho-Kinase Is Differentially Expressed in the Adipose Tissue of Rodent and Human in Response to Aging, Sex, and Acute Exercise

2024; Oxford University Press; Volume: 79; Issue: 3 Linguagem: Inglês

10.1093/gerona/glae001

1758-535X

Vitor Rosetto Muñoz, Renan Fudoli Lins Vieira, Carlos K. Katashima, Rafael Calais Gaspar, Marsel Lino, Joice Cristina dos Santos Trombeta, Renata Garbellini Duft, Ana Paula Azevêdo Macêdo, Adelino Sánchez Ramos da Silva, Eduardo R. Ropelle, Leandro Pereira de Moura, Dennys E. Cintra, Mara Patrícia Traina Chacon‐Mikahil, Cláudia Regina Cavaglieri, José Rodrigo Pauli,

Adipokines, Inflammation, and Metabolic Diseases

White adipose tissue (WAT) controls energy storage, expenditure, and endocrine function. Rho-kinase (ROCK) is related to impaired thermogenesis, downregulation of preadipocyte differentiation, and adipokine production. Furthermore, WAT ROCK responds to metabolic stress from high-fat diets or diabetes. However, ROCK distribution in adipose depots and its response to aging and sex remain unclear. Thus, we aim to investigate ROCK function in adipose tissue of rodent and human in response to aging and sex. We observed specific differences in the ROCK1/2 distribution in inguinal WAT (ingWAT), perigonadal WAT (pgWAT), and brown adipose tissue of male and female rodents. However, ROCK2 expression was lower in female ingWAT compared with males, a fact that was not observed in the other depots. In the pgWAT and ingWAT of male and female rodents, ROCK activity increased during development. Moreover, middle-aged female rodents and humans showed downregulation in ROCK activity after acute physical exercise. Interestingly, ROCK levels were associated with several inflammatory markers both in rats and humans WAT (Nfkb1, Tnf, Il1b, Il6, and Mcp1). Induction of cell senescence by etoposide elevates ROCK activity in human preadipocytes; however, silencing ROCK1/2 demonstrates improvement in the inflammatory and cell senescence state. Using public databases, several pathways were strongly associated with ROCK modulation in WAT. In summary, WAT ROCK increases with development in association with inflammatory markers. Further, ROCK activity was attenuated by acute physical exercise, implicating it as a possible therapeutic target for metabolism improvement mediated by adipose tissue inflammatory state changes.