Effects of low-fat and high-fat diets supplemented with omega-3 polyunsaturated fatty acids on liver fatty acids in a mouse model of chemotherapy
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Date
2021-05
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The Ohio State University
Abstract
Background: Over two thirds of breast cancer survivors are overweight or obese. Obesity can lead to insulin resistance, which may be aggravated by chemotherapy. Increasing dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) alters liver fatty acids (FAs) and can potentially reduce insulin resistance.
Methods: The effects of a high-fat diet with added long chain n-3 PUFAs on liver FAs and insulin resistance were investigated in a mouse model of chemotherapy. Female mice (n=48) were ovariectomized and assigned to one of three diets for 7 weeks: low-fat (LF), high-fat (HF), or high-fat diet with n-3 PUFAs (HFn-3). Mice received vehicle (saline) or chemotherapy injection (doxorubicin + cyclophosphamide) by tail vein during weeks 4 and 6. Fasting blood glucose and serum insulin were measured. Mice were sacrificed at week 7. Liver FAs were extracted, methylated and analyzed for relative fatty acid content using gas chromatography. Data were analyzed by 2-way ANOVA (diet and injection as two factors) and a t-test was run for post-hoc comparisons. FA data were log transformed and Pearson Correlations were used to assess associations with Homeostatic Model Assessment of Insulin Resistances (HOMA-IR).
Results: There were significant main effects of diet and injection on liver FAs. As expected, C20:5n3, C22:5n3, C22:6n3, and total n-3 PUFAs were highest in HFn-3 diet group (p<0.0001 for all). Total saturated fatty acids (SFAs) were also highest in HFn-3 diet group (p<0.05). C20:2n6, C20:4n6, and C22:4n6 were highest in HF group (p<0.003 for all), and C20:3n6 was higher in LF and HF groups than HFn-3 group (p<0.0001). C16:1n7, C18:1n7, C20:1n9, total monounsaturated fatty acids (MUFAs), total n-9 FAs were highest in LF diet group (p<0.0004 for all). C18:0 was higher in HF and HFn-3 groups than LF group (p<0.0002). C18:0, C20:0, C20:2n6, C20:4n6, C22:4n6, C22:6n3, total n-3 PUFAs, and total saturated fatty acids (SFAs) were higher in mice receiving chemotherapy (p<0.04 for all). C14:0, C18:1n9, C16:1n7, total MUFAs, and total n-9 FAs were higher in mice receiving saline injections (p<0.02 for all). Significant interaction effects of diet and injection were found for three liver PUFAs: C18:2n6, C18:3n6, C18:3n3 (p<0.04 for all); these same three PUFAs were also positively correlated with HOMA-IR (p<0.03 for all) and serum insulin (p<0.05 for all).
Conclusion: Feeding long chain n-3 PUFAs resulted in relatively higher long-chain n-3 PUFAs and total SFAs, and lower n-6 PUFAs and total MUFAs in the liver. Chemotherapy increased total SFAs and certain long-chain n-6 and n-3 PUFAs in the liver. Three 18 carbon PUFAs were significantly lowered by chemotherapy in HF and HFn-3 diets compared to vehicle mice and were associated with worse insulin resistance scores in this preliminary analysis. Further investigation of effects of liver FAs on insulin resistance during chemotherapy is warranted.
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1st Place, Food Sciences and Nutrition Category, 26th Denman Undergraduate Research Forum
Keywords
chemotherapy, insulin resistance, polyunsaturated fatty acids, breast cancer