Effects of Different Dietary Fatty Acids on the Fatty Acid Compositions and the Expression of Lipid Metabolic-Related Genes in Mammary Tumor Tissues of Rats

Abstract

In this study, the effects of dietary fatty acids on the fatty acid compositions and lipid metabolic-related genes expression in N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinogenesis were evaluated. The 50-day-old female Sprague-Dawley rats were intervened by different dietary fats (15% wt/wt), including saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), n-6 polyunsaturated fatty acid (PUFA), n-3 PUFA, 1:1 n-6/n-3, 5:1 n-6/n-3, 10:1 n-6/n-3, and 1:2:1 S/M/P (1:1 n-6/n-3), alone or in combination with MNU. There was no mammary tumor occurrence in the control and MNU-treated n-3 PUFA groups after 18 wk. n-3 PUFA diet retarded the weight growth of rats. 1:1 n-6/n-3 diet significantly reduced the MNU-induced tumor incidence and tumor multiplicity compared with SFA, MUFA, n-6 PUFA, 5:1 n-6/n-3, 10:1 n-6/n-3 and 1:2:1 S/M/P diets (42.86% vs. 83.33%–92.31%, 0.79 vs. 2.62–2.85, P < 0.01). Additionally, 1:1 n-6/n-3 diet substantially increased cis-5,8,11,14,17-eicosapentaenoic acid and cis-4,7,10,13,16,19-docosahexaenoic acid levels, whereas it decreased C20:4 level and the mRNA expressions of fatty acid synthase, Cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX) in mammary tissues (P < 0.05). These results suggest that 1:1 n-6/n-3 in the diet is effective in the prevention of mammary tumor development by increasing the n-3 PUFA content and reducing the expression of lipid metabolic-related genes.

ACKNOWLEDGMENT

This study was supported by the National Natural Science Foundation of China (Grant 30500408) and Danone Nutrition Foundation.

Notes

^a Values are expressed as the percentage of total fatty acids.

^a Abbreviations are as follows: ∑, sum; SFA, saturated fatty acids; ∑ UFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids; ∑ -6, n-6 PUFA; ∑ -3, n-3 PUFA; n-6/n-3, ratio of n-6 to n-3 PUFA.

^a Abbreviations are as follows: PUFA, polyunsaturated fatty acids; MNU, N-methyl-N-nitrosourea; SFA, saturated fatty acid; MUFA, monounsaturated fatty acids; n, sample size; n ^d , the number of rat deaths during the experimental period. P < 0.01 compared to the SFA, MUFA, n-6 PUFA, 5:1 n-6/n-3, 10:1 n-6/n-3, and 1:2:1 S/M/P diet groups.

^b The tumor volume (c.c.) was measured using the formula V = (4/3)π (D1/2) (D2/2) (D3/2), where D1, D2, and D3 are the 3 diameters of the tumor.

^c 1 rat escaped at the 3rd wk after MNU.

^d P < 0.01 compared to the SFA, MUFA, n-6 PUFA, 5:1 n-6/n-3, 10:1 n-6/n-3, and 1:2:1 S/M/P diet group.

^a Abbreviations are as follows: SFA, saturated fatty acids; MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids; ND, not detected. After lipid extraction, the fatty acid contents of each lipid fraction were analyzed and calculated with the internal standard qualitative analysis. These data were expressed as the absolute content in mammary adipose tissue (μ g/mg) and mean ± SD (n = 5). Values with different subscript letters in a line were significantly different at P < 0.05 by 1-way analysis of variance test.

^a Abbreviations are as follows: MNU, N-methyl-N-nitrosourea; SFA, saturated fatty acids; MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids; ND, not detected. After lipid extraction, the fatty acid contents of each lipid fraction were analyzed and calculated with the internal standard qualitative analysis. These data were expressed as the absolute content in mammary adipose tissue (μ g/mg) and mean ± SD (n = 5). Values with different subscript letters in a line were significantly different at P < 0.05 by 1-way analysis of variance test.