Exercise-induced irisin induces thermogenesis in cancer-associated adipocytes and affects lipid metabolism in Tnbc

Purpose: To verify that irisin may inhibit the development of TNBC by affecting lipid metabolism in cancer-associated adipocytes (CAAs) and tumor cells. Methods: Twelve general grade 8-week-old, female mammary carcinoma-loaded NOD/SCID mice were completely randomized into four groups: control group, irisin injection group, exercise intervention group, and sh-FNDC5 + exercise intervention group. The experimental intervention was 3 weeks. At the end of the experimental intervention, mouse tumor volume, local temperature, and fatty acid oxidation levels in adipocytes and cancer cells surrounding the tumor were measured. Results: One-way ANOVA showed that there was no statistically significant difference between the before and after comparisons of tumor volume in each group of mice. Notably, local mouse temperatures showed that peritumor temperatures were significantly higher in the irisin-injected group (39.78 ± 0.82 vs. 37.54 ± 0.49, 39.78 ± 0.82 vs. 37.51 ± 0.80, P < 0.001) and the exercise-intervention group compared to the control group (40.08 ± 0.64 vs. 38.08 ± 0.66,40.08 ± 0.64 vs. 38.17 ± 0.57, P < 0.001) were significantly higher than the tumor center and skin temperatures. sh-FNDC5+ mice in the exercise intervention group also had higher peritumor temperatures than the skin (38.82 ± 0.29 vs. 38.38 ± 0.22, P < 0.05) and tumor center temperatures. In terms of fatty acid oxidation level of peritumor adipocytes, it was significantly higher in irisin injection group and exercise group compared to control group (0.13 ± 0.01 vs.0.17 ± 0.00, P < 0.05; 0.13 ± 0.01 vs.0.19 ± 0.01, P < 0.05), and there was no significant change in sh-FNDC5+ exercise intervention group. In terms of fatty acid oxidation levels in cancer cells, they were decreased in the irisin injection and exercise groups compared to the control group (0.92 ± 0.05 vs. 0.77 ± 0.09, P < 0.001; 0.92 ± 0.05 vs. 0.71 ± 0.09, P < 0.001), and were significantly elevated in the sh-FNDC5+ exercise intervention group (0.92 ± 0.05 vs. 1.29 ± 0.08, P < 0.001). Conclusions: Exercise-induced irisin and exogenous irisin injections may play a role in inhibiting the development of triple-negative breast cancer by activating the thermogenic function of CAAs as well as affecting the reprogramming of tumor lipid metabolism.