Impact of prehabilitation on adipose tissue remodelling during FLOT chemotherapy

• Autor(a) principal: Barbosa, Samuel da Silva
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/37857
• topic: Gastric cancer; Chemotherapy; Neoadjuvant treatment; Adipose tissue; Prehabilitation; Exercise; Adipose tissue metabolism; Lipolysis; Thermogenesis

Gastric cancer (GC) is associated with high mortality rates and poor quality of life of patients. Chemotherapy is largely used in the treatment of GC, however, it is responsible for changes in body composition, such as the loss of adipose tissue (AT), both visceral (VAT) and subcutaneous (SAT), and even skeletal muscle (SM), which is associated with decreased overall survival (OS). Effectively, the AT is remodeled by various chemotherapy regimens with consequent increased lipolysis, decreased de novo lipogenesis and eventually the browning of white AT (WAT) which is associated with increased thermogenesis. This dissertation aimed to understand the impact of a prehabilitation program based on general recommendations of physical activity (P1) vs. strength, aerobic and breathing exercises (P2), as a supplement to the usual treatment (medical optimization, nutritional and psychological monitoring) on the remodelling of AT during neoadjuvant chemotherapy with Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel (FLOT) in patients with stomach cancer. For this purpose, 40 patients treated with FLOT were followed, n=16 were allocated to the P2 group and n=18 to P1. The remaining 6 patients were not considered eligible to perform exercise/physical activity and underwent only the usual treatment (SFF). Visceral AT samples were collected before and after treatment with FLOT for histological and biochemical analysis. Results showed no significant changes in the levels of adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL) in the AT, which seems to explain the maintenance of the percentage of fat mass assessed by bioimpedance. Moreover, an increase in uncoupling Protein-1 (UCP-1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) content was found in the AT, although not significant, in the P2 group. Additionally, in patients treated with FLOT it was observed that the increase in UCP-1 seems to explain the decrease in BMI. However, in the future it will be necessary to increase the number of patients studied and to carry out a more in-depth analysis of the molecular mechanisms modulated in the AT by FLOT and prehabilitation.