Dataset Information

Fish oil mitigates myosteatosis and improves chemotherapy efficacy in a preclinical model of colon cancer.

ABSTRACT:

Background

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.

Methods

Female 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.

Results

Feeding 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).

Conclusion

Long 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.

SUBMITTER: Almasud AA

PROVIDER: S-EPMC5568380 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Fish oil mitigates myosteatosis and improves chemotherapy efficacy in a preclinical model of colon cancer.

Almasud Alaa A AA Giles Kaitlin H KH Miklavcic John J JJ Martins Karen J B KJB Baracos Vickie E VE Putman Charles T CT Guan Leluo L LL Mazurak Vera C VC

PloS one 20170823 8

<h4>Background</h4>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.<h4>Methods</h4>Female 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). Ch ...[more]

PMID: 28832677

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Project description:Accelerated loss of adipose tissue in cancer is associated with shorter survival, and reduced quality of life. Evidence is emerging suggesting tumour association with alterations in adipose tissue, but much less is known about drug-related mechanisms contributing to adipose atrophy. Identification of mechanisms by which tumour and cancer treatments, such as chemotherapy, affect adipose tissue are required to develop appropriate therapeutic interventions to prevent fat depletion in cancer. This pre-clinical study aimed to assess alterations in adipose tissue during the clinical course of cancer.Fischer 344 rats bearing the Ward colorectal tumour were euthanized before chemotherapy, after 1- cycle, or 2-cycles of a combination chemotherapy consisting of Irinotecan (CPT-11) combined with 5-fluorouracil (5-FU), which recapitulates first line treatment for human colorectal cancer. Periuterine adipose tissue was isolated. Healthy rats served as a reference group. Histological analysis (hematoxylin and eosin), Real-time PCR (TaqMan) and proteomic analysis (LC-MS/MS) were performed.Larger adipocytes (3993.7?±?52.6 ?m2) in tumour-bearing animals compared to the reference group (3227.7?±?36.7 ?m2; p?<?0.001) was associated with reduced expression of proteins involved in mitochondrial fatty acid oxidation. The presence of a tumour has a significant effect on phospholipid but not triglyceride fatty acid composition. There were greater proportions of saturated fatty acids concurrent with lower monounsaturated fatty acids within the PL fraction of adipocytes in tumour-bearing animals. Chemotherapy treatment decreased the size of adipocytes (2243.9?±?30.4 ?m2; p?<?0.001) and led to depletion of n-3 polyunsaturated fatty acids in adipose tissue triglyceride. Evaluation of the proteome profile revealed decreased expression of proteins involved in ATP generation, ?-oxidation, and lipogenesis. Overall, adipose tissue may not be able to efficiently oxidize fatty acids to provide energy to maintain energy demanding pathways like lipogenesis inside the tissue.In conclusion, metabolic adaptations to mitochondrial impairment may contribute to diminished lipid storage capacity of adipose tissue following chemotherapy delivery.

Dataset Information

Fish oil mitigates myosteatosis and improves chemotherapy efficacy in a preclinical model of colon cancer.

Background

Methods

Results

Conclusion

Publications

Fish oil mitigates myosteatosis and improves chemotherapy efficacy in a preclinical model of colon cancer.

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