Role of the sympathetic nervous system in cancer-associated cachexia and tumor progression in tumor-bearing BALB/c mice

• Published in: BMC neuroscience 2024-08, Vol.25 (1), p.37-9
• Main Authors: Gutierrez-Leal, Isaias, Caballero-Hernández, Diana, Orozco-Flores, Alonso A, Gomez-Flores, Ricardo, Quistián-Martínez, Deyanira, Tamez-Guerra, Patricia, Tamez-Guerra, Reyes, Rodríguez-Padilla, Cristina
• Format: Article
• Language: English
• Subjects: 6-Hydroxydopamine; Adipose tissue; Adrenergic system; Animal models; Animals; Beta blockers; Body fat; Body Mass Index; Cachexia; Cachexia - etiology; Cachexia - metabolism; Cachexia - pathology; Cancer; Cancer cachexia; Cancer therapies; Cell Line, Tumor; Chemotherapy; Cytokines; Development and progression; Disease Progression; Food; Food intake; Gelatinase B; Gene expression; Health aspects; Inflammation; Interleukin-6 - metabolism; Ion Channels - metabolism; Lymphoma; Male; Matrix Metalloproteinase 9 - metabolism; Medical research; Medicine, Experimental; Mice; Mice, Inbred BALB C; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Morphology; Neoplasms - complications; Neoplasms - metabolism; Neoplasms - pathology; Nervous system; Nervous system, Sympathetic; Oxidopamine; Physiological aspects; Sympathectomy; Sympathectomy, Chemical; Sympathetic nervous system; Sympathetic Nervous System - metabolism; Sympathetic Nervous System - physiopathology; Tumors; Uncoupling Protein 1 - metabolism; γ-Interferon
• ISSN: 1471-2202; 1471-2202
• DOI: 10.1186/s12868-024-00887-8

Adipose and muscle tissue wasting outlines the cachectic process during tumor progression. The sympathetic nervous system (SNS) is known to promote tumor progression and research suggests that it might also contribute to cancer-associated cachexia (CAC) energetic expenditure through fat wasting. We sympathectomized L5178Y-R tumor-bearing male BALB/c mice by intraperitoneally administering 6-hydroxydopamine to evaluate morphometric, inflammatory, and molecular indicators of CAC and tumor progression. Tumor burden was associated with cachexia indicators, including a 10.5% body mass index (BMI) decrease, 40.19% interscapular, 54% inguinal, and 37.17% visceral adipose tissue loss, a 12% food intake decrease, and significant (p = 0.038 and p = 0.0037) increases in the plasmatic inflammatory cytokines IL-6 and IFN-γ respectively. Sympathectomy of tumor-bearing mice was associated with attenuated BMI and visceral adipose tissue loss, decreased interscapular Ucp-1 gene expression to basal levels, and 2.6-fold reduction in Mmp-9 relative gene expression, as compared with the unsympathectomized mice control group. The SNS contributes to CAC-associated morphometric and adipose tissue alterations and promotes tumor progression in a murine model.