Increased Expression of Serca2b in the Adipose Tissue of a Cancer Cachexia Model

Cancer cachexia is a complication that emerges in approximately 50-80% of patients with advanced cancer, characterized by symptoms such as lipoatrophy, skeletal muscle loss, metabolic abnormalities, and anorexia. While UCP1, a mitochondrial uncoupling protein, is implicated in lipolysis associated with cancer cachexia, the involvement of other thermogenic proteins remains unclear. In this exploratory study, we examined the expression of thermogenic genes in a mouse model of cancer cachexia.

Tumor-bearing mice were generated by injecting Colon-26 cells (C26) into the right flank of male BALB/c mice. The body weight and temperature, tumor volume, and food intake of these mice were recorded three times a week. After 46 days of C26 administration, the adipose tissue, muscle, tumor, and blood were isolated from the mice and analyzed for thermogenic gene expression and biochemical parameters.

Quantitative reverse transcription PCR analysis revealed increased expression of Serca2b, a gene associated with Ucp1 independent thermogenesis, in adipose tissue of C26-bearing mice. A positive correlation between Serca2b and Ucp1 mRNA levels was observed. In addition, Serca2b expression was not responsive to norepinephrine in differentiated 3T3-L1 adipocytes.

Although the functional relevance of Serca2b up-regulation remains to be elucidated, these findings suggest a potential role for SERCA2b in adipose tissue remodeling during cachexia. This preliminary observation may serve as a foundation for future studies investigating calcium cycling and non-canonical thermogenesis in the pathophysiology of cancer cachexia.