Effect of aerobic exercise training on the Irisin/MAPK pathway in the perivascular adipose tissue of obese female mice

• Grant number: 24/14424-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2025
• End date: July 31, 2028
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Andréia Delbin
• Grantee: Teresa Maria da Ré Silva
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Perivascular adipose tissue (PVAT) plays endocrine and paracrine roles, and physical exercise modulates its secretory pattern, affecting vascular response. In obesity, PVAT becomes dysfunctional, primarily secreting pro-inflammatory factors that contribute to the development of cardiovascular complications. Skeletal muscle exhibits an endocrine function similar to PVAT, and during physical exercise, it releases irisin, which has antioxidant, anti-inflammatory, and pro-angiogenic effects that can mitigate obesity-related dysfunctions. The mechanisms responsible for PVAT dysfunction in obesity and the role of the irisin/MAPK pathway are not yet fully elucidated, with most studies conducted on males. Thus, this study aims to evaluate the effects of aerobic exercise training on the irisin/MAPK pathway in the PVAT of obese female mice. Female C57BL6/JUnib mice will be fed either a standard or high-fat diet for 16 weeks and subjected to a moderate-intensity treadmill aerobic training protocol for 8 weeks. Treatment with CycloRGDyk, described as an irisin receptor blocker, will also be administered. Relaxation and contraction responses in thoracic aortic rings with and without PVAT will be evaluated. Histological analysis for tissue morphology characterization, capillary quantification, reactive oxygen species (ROS) generation analysis, and vascular nitric oxide production will be performed on thoracic aortic PVAT (tPVAT). Protein expression will be analyzed in the gastrocnemius muscle (PGC-1-± and FNDC5), thoracic aorta (AMPK, Akt, eNOS, phospho-eNOSser1177), and tPVAT (UCP1, PGC-1±, FNDC5, p44/42 MAPK (ERK1/2), p38 MAPK, phospho-p38 MAPKthr180/tyr182, integrin ²5, integrin ±V, adiponectin, HO-1). Gene expression of angiogenesis markers (Vegfa, Vegfr2, Jag1, and Angpt2) will be analyzed. Serum concentrations of glucose, 17²-estradiol, irisin, TBARS, superoxide dismutase (SOD), and catalase (CAT) will also be measured.