# Impact of obesity on chemotherapy-induced muscle mitochondrial dysfunction > **NIH NIH F31** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2024 · $12,458 ## Abstract PROJECT SUMMARY Obesity increases the risk of cancer; thus, individuals that are obese are more likely to undergo chemotherapy in their lifetime. However, there is a dearth of literature on the impact of weight status on cancer patient life quality and functional capacity throughout treatment. For instance, our knowledge of the impact of obesity on cancer and chemotherapy-induced cachexia - the unintentional loss of lean mass, which directly contributes to functional dependency, poor treatment outcomes, and decreased survival – is incomplete. An “obesity paradox” has been postulated; however, the epidemiology remains equivocal on the benefits/detriments of a high pre-treatment body weight and body mass index. While obesity and cachexia are diseases at opposite ends of the weight spectrum, these pathologies share some underlying perturbations (e.g. mitochondrial dysfunction) that may exacerbate functional decrements when these morbidities co-occur. Our lab made the novel and significant discovery that obese mice, dosed for lean mass, were unable to survive 2-3 cycles of the chemotherapeutic, 5 fluorouracil (5FU). Indeed, contrary to what has been suggested, we discovered that obese mice are not protected against chemotherapy-induced cachexia and show exacerbated skeletal muscle toxicities. Disruptions to mitochondria are 1) central to chemotherapy-induced skeletal muscle mass loss, and 2) are known to be existent with obesity and metabolic dysfunction; however, mitochondrial dysfunction and resultant functional deficits have not been assessed when these morbidities co-occur. Antioxidants have been shown to improve mitochondrial function. Indeed, we have shown that the antioxidant dietary compound, quercetin, can reduce cancer, cancer cachexia, and chemotherapy-induced fatigue, and can increase mitochondrial function in healthy mice. Thus, quercetin may hold promise as a dietary strategy to treat cachexia associated with cancer and its therapies in the obese condition. The primary goal of my proposed F31 is to 1) understand the impact of obesity on 5FU-induced skeletal muscle dysfunction and 2) provide mechanistic and therapeutic insights aimed at better improving 5FU tolerance with obesity. My central hypothesis is that 5FU-induced mitochondrial loss and dysfunction is exacerbated with an obese phenotype and intervening with quercetin will mitigate the deleterious effects of 5FU on skeletal muscle. To test this hypothesis, I propose three related but independent specific aims: 1) Examine the impact of obesity on cancer and 5FU-induced cachexia and function loss; 2) Determine the role of mitochondria in obesity-exacerbated 5FU toxicities; and 3) Explore the utility of dietary quercetin on improving 5FU treatment tolerance and off- target toxicities with obesity. The proposed studies align with my training aims and will provide me with the opportunity to gain expertise in obesity phenotyping and natural compounds as therapeutics, mitochondrial healt... ## Key facts - **NIH application ID:** 10884210 - **Project number:** 5F31CA278490-02 - **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA - **Principal Investigator:** Thomas Cardaci - **Activity code:** F31 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $12,458 - **Award type:** 5 - **Project period:** 2023-07-01 → 2024-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10884210 ## Citation > US National Institutes of Health, RePORTER application 10884210, Impact of obesity on chemotherapy-induced muscle mitochondrial dysfunction (5F31CA278490-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10884210. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*