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

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Munoz, Vitor Rosetto ; Vieira, Renan Fudoli Lins ; Katashima, Carlos Kiyoshi ; Gaspar, Rafael Calais ; Lino, Marsel ; Trombeta, Joice Cristina dos Santos ; Duft, Renata Garbellini ; Azevedo Macedo, Ana Paula ; da Silva, Adelino Sanchez Ramos ; Ropelle, Eduardo Rochete ; de Moura, Leandro Pereira ; Cintra, Dennys Esper ; Chacon-Mikahil, Mara Patricia Traina ; Cavaglieri, Claudia Regina ; Pauli, Jose Rodrigo

• Document type: Journal article
• Source: JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES; v. 79, n. 3, p. 10-pg., 2024-02-20.

Abstract

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. (AU)

• FAPESP's process: 20/13443-1 - Implications of aerobic exercise on the Notch 1 signaling pathway and regulation of lipogenesis and gluconeogenesis in the liver
• Grantee: José Rodrigo Pauli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/08692-5 - Analysis of the rev-erb-alpha protein interactome through immunoprecipitation of target protein and identification of possible ligands by mass spectrometry in cell culture
• Grantee: Vitor Rosetto Muñoz
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/20872-6 - Effects of physical exercise on Rock protein signaling pathway, and lipogenic regulation and gluconeogenesis in the liver of aged rats
• Grantee: José Rodrigo Pauli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/18488-8 - The role of physical exercise on molecular pathways of glucose uptake in GLUT-4 knockout mice
• Grantee: José Rodrigo Pauli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/11820-5 - Nr1d1 function on the aging-associated Sarcopenia
• Grantee: Adelino Sanchez Ramos da Silva
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/26000-2 - The role of Rock protein on glucose uptake in the skeletal muscle of exercised rodents during the aging process
• Grantee: Vitor Rosetto Muñoz
• Support Opportunities: Scholarships in Brazil - Master