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

Author:

Muñoz Vitor Rosetto12,Vieira Renan Fudoli Lins1,Katashima Carlos Kiyoshi1,Gaspar Rafael Calais1,Lino Marsel2,Trombeta Joice Cristina dos Santos3,Duft Renata Garbellini3,Azevêdo Macêdo Ana Paula1,da Silva Adelino Sanchez Ramos45,Ropelle Eduardo Rochete16,de Moura Leandro Pereira1,Cintra Dennys Esper67,Chacon-Mikahil Mara Patricia Traina3,Cavaglieri Cláudia Regina3,Pauli José Rodrigo16

Affiliation:

1. Laboratory of Molecular Biology of Exercise, University of Campinas (UNICAMP) , Limeira, São Paulo , Brazil

2. Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School , Boston, Massachusetts , USA

3. Exercise Physiology Laboratory (FISEX), Faculty of Physical Education, University of Campinas (UNICAMP) , Campinas, São Paulo , Brazil

4. Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP) , Ribeirão Preto, São Paulo , Brazil

5. School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP) , Ribeirão Preto, São Paulo , Brazil

6. OCRC—Obesity and Comorbidities Research Center, University of Campinas (UNICAMP) , Campinas, São Paulo , Brazil

7. Laboratory of Nutritional Genomics, University of Campinas (UNICAMP) , Limeira, São Paulo , Brazil

Abstract

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.

Publisher

Oxford University Press (OUP)

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