Abstract
BackgroundThis study aimed to assess whether feeding a diet containing fish oil was efficacious in reducing tumor- and subsequent chemotherapy-associated myosteatosis, and improving tumor response to treatment.MethodsFemale Fischer 344 rats were fed either a control diet for the entire study (control), or switched to a diet containing fish oil (2.0 g /100 g of diet) one week prior to tumor implantation (long term fish oil) or at the start of chemotherapy (adjuvant fish oil). Chemotherapy (irinotecan plus 5-fluorouracil) was initiated 2 weeks after tumor implantation (cycle-1) and 1 week thereafter (cycle-2). Reference animals received no tumor or treatment and only consumed the control diet. All skeletal muscle measures were conducted in the gastrocnemius. To assess myosteatosis, lipids were assessed histologically by Oil Red O staining and total triglyceride content was quantified by gas chromatography. Expression of adipogenic transcription factors were assessed at the mRNA level by real-time RT-PCR.ResultsFeeding a diet containing fish oil significantly reduced tumor- and subsequent chemotherapy-associated increases in skeletal muscle neutral lipid (p<0.001) and total triglyceride content (p<0.03), and expression of adipogenic transcription factors (p<0.01) compared with control diet fed animals. The adjuvant fish oil diet was as effective as the long term fish oil diet in mitigating chemotherapy-associated skeletal muscle fat content, and in reducing tumor volume during chemotherapy compared with control fed animals (p<0.01).ConclusionLong term and adjuvant fish oil diets are equally efficacious in reducing chemotherapy-associated myosteatosis that may be occurring by reducing expression of transcription factors involved in adipogenesis/lipogenesis, and improving tumor-response to chemotherapy in a neoplastic model.
Highlights
Clinical practice aims to improve the effectiveness of chemotherapeutics to reduce tumor growth while mitigating harmful side effects
The adjuvant fish oil diet was as effective as the long term fish oil diet in mitigating chemotherapy-associated skeletal muscle fat content, and in reducing tumor volume during chemotherapy compared with control fed animals (p
The current study aimed to identify a preclinical model of cancer-associated myosteatosis and apply this model to investigate the effects of dietary EPA and DHA on tumor- and subsequent chemotherapy-associated fat content of skeletal muscle, as well as the tumor response to chemotherapy
Summary
Clinical practice aims to improve the effectiveness of chemotherapeutics to reduce tumor growth while mitigating harmful side effects. One approach to improve the therapeutic index of antineoplastic therapies is to combine cytotoxic drugs with adjuvant factors that enhance anti-tumor efficacy and reduce harmful side effects. Pathological alterations in skeletal muscle have been identified in cancer patients undergoing treatment, including muscle loss and fat accumulation [1,2,3,4,5,6,7]. Low skeletal muscle density, which reflects high skeletal muscle fatty infiltration, is associated with shorter progression- and disease-free survival [2,6], and overall survival [2,4,5] in cancer patients treated with various therapies including chemotherapy. This study aimed to assess whether feeding a diet containing fish oil was efficacious in reducing tumor- and subsequent chemotherapy-associated myosteatosis, and improving tumor response to treatment
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