Effects of a Leucine-Rich Diet and Spontaneous Physical Activity on Cachexia Induced by Walker 256 Tumor in Wistar Rats Treated with Chemotherapy

• Grant number: 25/18917-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2025
• End date: November 30, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Cristina Cintra Gomes Marcondes
• Grantee: Sofia Serrano Millan da Silva
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 23/00608-0 - MOLECULAR, TRANSCRIPTOMIC, PROTEOMIC AND METABOLOMIC ASPECTS OF CAQUEXIA IN A PRE-CLINICAL AND CLINICAL MODEL, AP.TEM

Abstract

Cancer is characterised by rapid and uncontrolled cell growth, with the ability to invade tissues and organs, making it one of the leading causes of mortality worldwide. As a complex disease, cancer can cause various systemic complications, including cachexia- a multifactorial syndrome characterised by involuntary body weight loss, progressive depletion of skeletal muscle mass, and associated symptoms such as fatigue and anorexia. These factors substantially impair the patient's nutritional status, diminishing both quality of life and survival. Previous studies indicate that a leucine-rich diet has the potential to minimise the effects of cachexia by stimulating muscle protein synthesis and reducing muscle degradation. Walker 256 tumour is widely used as an experimental model of cachexia, and reveals a useful preclinical model for investigating therapeutic interventions. Furthermore, combining dietary supplementation with chemotherapy, the conventional treatment for cancer, may expand knowledge regarding its effects in counteracting tumour progression. Considering that physical inactivity is one of the main preventable risk factors for cancer development and prognosis, spontaneous physical activity, assessed through the use of a running wheel, will be investigated for its possible benefits in attenuating cachexia, reducing chemotherapy-induced adverse effects, and improving the quality of life of cancer-bearing hosts. Therefore, this project aims to conduct a preclinical study to evaluate the effects of leucine supplementation and spontaneous physical activity on the progression of Walker 256 tumour-induced cachexia in rats treated with chemotherapeutic agents. Adult male Wistar rats will be distributed into eight groups: 1 - control group, healthy animals (C); 2 - exercised group (E); 3 - Walker 256 tumour group (W); 4 - Walker 256 tumour + exercise (WE); 5 - Walker 256 tumour + chemotherapy treatment + exercise (WQE); 6 - Walker 256 tumour + chemotherapy treatment + leucine-rich supplementation + spontaneous physical activity (WLQE). The study will evaluate the evolution of body weight and muscle mass, as well as food intake and motor activity (including movement, speed, and wheel activity time) compared with sedentary animals, and body composition over a time course (days 7, 14, and 21). After euthanasia (21 days of tumour progression), the chemical composition of muscle, cardiac, tumour, and carcass tissues will be analysed.