Abstract 415: Effect of aerobic and resistance exercise on the mitochondrial peptide MOTSc in Hispanic and non-Hispanic breast cancer survivors

Abstract Background MOTS-c is a mitochondrial derived peptide with exercise mimetic activity that elicits beneficial effects on metabolism and exercise capacity. MOTS-c stimulates glucose utilization, fat-oxidization, reduces inflammation, and protects against experimental models of metabolic disease. Furthermore, MOTS-c effects in humans are affected by race, potentially via ethnic-specific mtDNA variations. Women treated for breast cancer are at an increased risk for risk for cardiovascular disease, diabetes and obesity, due to side effects of cancer-treatments. Exercise mitigates many of these side effects, but the role of MOTS-c regulation by exercise among breast cancer survivors (BCS) of varying ethnicities is unknown. We examined the effects of a 16-week aerobic and resistance exercise intervention on MOTS-c in Hispanic and Non-Hispanic BCS. Methods BCS (Stage I-III) were randomized to exercise (n=50) or standard care (n=50). The intervention promoted supervised, progressive moderate-vigorous aerobic and resistance exercise thrice weekly for 16 weeks. Aerobic exercise was performed at 65-85% maximum heart rate. Resistance exercise was performed in circuit-fashion with 3 sets of 10-15 repetitions including upper and lower body exercises at 65-70% 1-repetition maximum. Fasting blood draws were obtained at baseline and post-intervention (4 months). Body composition was assessed by dual energy x-ray absorptiometry. MOTS-c was analyzed in plasma using an in-house ELISA. Within and between group differences were assessed by paired t-test and repeated measures ANOVA. Pearson's correlation was computed to assess the association between MOTS-c and metabolic biomarkers. ResultsTwenty-five Hispanic BCS and 24 non-Hispanic BCS (age 53.5±10.4 years) and BMI of 33.5±5.5 kg/m2 were included. Hispanic BCS were younger, of greater adiposity, had higher stage cancers, and had worse metabolic profiles at baseline compared to non-Hispanic BCS (p<0.001). Post-exercise, MOTS-c levels significantly increased when compared to baseline and the usual care group among NHBCS (p<0.01). Post-exercise levels of MOTS-c among non-Hispanic BCS were significantly associated with reductions in fat mass, body weight, HOMA-IR, CRP, and an increase in lean mass (p<0.01). MOTS-c did not significantly change following exercise among Hispanic BCS (p>0.05). Conclusions A 16-week aerobic and resistance intervention increased MOTS-c levels among non-Hispanic BCS but not Hispanic BCS. Non-Hispanic BCS who experience exercise-induced improvements in MOTS-c may also experience improved insulin sensitivity thereby reducing the risk for comorbid conditions. Despite poorer metabolic profiles, Hispanic BCS may not experience exercise-induced benefits on MOTS-c. Future trials should aim for reducing potential ethnic differences in cardiometabolic health. Citation Format: Christina M. Dieli-Conwright, Nathalie Sami, Mary K. Norris, Junxiang Wan, Hiroshi Kumagai, Pinchas Cohen. Effect of aerobic and resistance exercise on the mitochondrial peptide MOTSc in Hispanic and non-Hispanic breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 415.