INFLAMMATORY STATUS AND SATELLITE CELLS ACTIVITY IN MUSCULAR HYPERTROPHY IN GOTO-KAKIZAKI RATS

• Grant number: 24/14304-6
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2025
• End date: February 29, 2028
• Field of knowledge: Biological Sciences - Physiology - Physiology of Effort
• Principal Investigator: Rui Curi
• Grantee: Rui Curi
• Host Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil
• Associated researchers: Kaio Fernando Vitzel ; Laureane Nunes Masi ; Renata Gorjao ; Sandro Massao Hirabara ; Tania Cristina Pithon Curi

Abstract

Musculoskeletal disorders are frequent in diabetic patients and are associated with an imbalance between protein synthesis and degradation and impaired satellite cell activity. Despite this, the extensor digitorum longus (EDL) and soleus muscles of diabetic rats, when induced to hypertrophy by compensatory surgery, show mass muscle gain of the same magnitude as the control. Type 2 diabetes mellitus (DM2) exhibits insulin resistance commonly triggered by obesity and subclinical chronic inflammation. However, a considerable portion of the T2DM population is not obese; a condition mimicked in Goto-Kakizaki (GK) rats, developed in Japan by selective breeding of non-diabetic Wistar rats with mild glucose intolerance. Therefore, in the present study, we aim to investigate the inflammatory condition and the activity of satellite cells in the hypertrophy of the EDL and soleus muscles of GK rats and controls. After confirming the state of diabetes in the GK animals, both groups will be anesthetized and submitted to synergistic ablation surgery of the tibialis anterior muscle or tenotomy of the gastrocnemius muscle to induce hypertrophy of the EDL and soleus muscles, respectively. After 1, 3, 7, and 14 days of overload, the muscles will be collected. The EDL and soleus muscles will be weighed and then subjected to the following analyses: hematoxylin-eosin (morphological and cross-sectional area of muscle fibers), immunohistochemistry (CD68 and CD163), immunofluorescence (Pax7, myogenin, MHC1 and MHC2B), ELISA ( CXCL1, MCP1, TNF-±, IL-1², IL-6, VEGF, and CK), western blot (IL-4; IL-10; MyoD; MyF5; MyF6 and desmin) and RT-qPCR (CXCL1, MCP1, TNF -±, IL-6, VEGF, IL-1², IL-4, IL-10, and Pax7). The hypothesis to be tested is that muscle hypertrophy in GK animals reaches the same magnitude as in control animals due to compensation in the inflammatory muscle activity preinstalled in these animals, which may anticipate the activation and action of muscle satellite cells during tissue regeneration. (AU)