The effects of long-term aerobic exercise on prostate cancer-induced adipose tissue wasting: Browning to the rescue?

The loss of adipose tissue has been emerging as a key component of cancer-related body wasting. One of the underlying causes suggested for this loss is the browning of the white adipose tissue. However, exercise, a promising therapeutic strategy for cancer-related body wasting, might also promote white adipose tissue browning. It remains unclear how similar or distinct the browning process and its effects are when triggered by exercise in cancer compared to cancer alone. This study investigated the retroperitoneal adipose tissue remodeling in prostate cancer-induced body wasting with and without long-term aerobic exercise. For that, a chemically- and hormonally-induced prostate cancer protocol was implemented in male rats as a cancer-induced body wasting model, and a treadmill exercise protocol of 53 weeks was used as long-term aerobic exercise. Sedentary or exercised tumor-free rats were used as controls. The results revealed that prostate carcinogenesis induced body wasting and reduced the cross-sectional area (CSA) of adipocytes in retroperitoneal adipose tissue without increasing the levels of browning markers, suggesting wasting without browning. Aerobic exercise attenuated the development of prostate carcinogenesis-induced body wasting and decreased the CSA of the adipocytes while increasing their number. The reduced CSA was correlated with increased retroperitoneal adipose tissue levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and uncoupling protein 1 (UCP1), disclosing molecular adaptations compatible with an adipose tissue browning phenotype. These results suggest that long-term aerobic exercise induces adipose tissue remodeling that may counteract cancer-induced body wasting, highlighting the potential of physical activity in managing cancer-related metabolic changes.