| The associations between dietary n-3fatty acids, type2diabetes, breast cancer and other chronic diseases are still inconclusive. The present thesis investigated the associations of n-3fatty acids with type2diabetes, coronary heart disease, breast cancer and non-alcoholic fatty liver disease via evidence-based nutritional studies. We found that, compared with low intake, high intake of long-chain n-3fatty acids was associated with13%lower risk of type2diabetes in Asian populations, while it was associated with16%higher risk of type2diabetes in Western populations. In addition, long-chain n-3fatty acids were inversely associated with lower risk of breast cancer and non-alcoholic fatty liver disease. Risk of fatal coronary heart disease was inversely associated with dietary fish intake.Based on our findings, we hypothesized that gene-nutrient interaction may contribute to the opposite responses of type2diabetes risk to n-3fatty acids between Asian and Western populations. To examine the hypothesis and investigate related mechanims, we conducted further research in the following four parts:Part â… . Gene-nutrient interaction analysis was performed in a white population. Two genetic variants nearby PIK3CA:rs7645550and rs1183319, and two genetic variants at another gene PSMD3:rs4795413and rs8065443, were all found to interact with dietary n-3fatty acids or n-3:n-6ratio to modulate insulin resistance. In a Chinese population, significant interaction between PEPD variant rs3786897and n-3fatty acids on the risk of type2diabetes was found The positive association between rs3786897-A allele and risk of type2diabetes was significant only when erythrocyte level of n-3fatty acids was high.Part â…¡. Genome-wide complex trait analysis (GCTA) was conducted in a white population and a Puerto Rican population and found that the genome-wide genotype by environment interaction of dietary n-3fatty acids or erythrocyte n-3fatty acids contributed a significant variance to the total phenotypic variance of type2diabetes traits, including fasting insulin and insulin resistance. These results demonstrated the important role of the interaction between n-3fatty acids and genes in the development of type2diabetes.Part â…¢. A180day randomized controlled trial was conducted in Chinese patients with type2diabetes to examine effects of fish oil (rich in C20:5n-3and C22:6n-3) and flaxseed oil (rich in C18:3n-3) on the glucose and lipid metabolism. The results found that fish oil could improve the status of glucose and lipid metabolism, and increase plasma C20:5n-3and C22:6n-3levels, and also increase levels of plasma phytosterol metabolites, including campesterol and beta-sitosterol.Part â…£. Type2diabetic SD rat model was established to investigate the effects of8-week intervention of fish oil and flaxseed oil on glucose and lipid metabolism. The results indicated that fish oil could improve the status of plasma glucose and insulin resistance. In addition, fish oil may significantly improve insulin signaling pathway, by increasing mRNA expression of key genes in the pathway.In conclusion, the present thesis found that long-chain n-3fatty acids were associated with lower risk of type2diabetes in Asians, but higher risk of type2diabetes in Western populations. The different response of type2diabetes to n-3fatty acids may be attributed to the gene-nutrient interaction. Dietary n-3fatty acids were also suggested to improve glucose and lipid metabolism in Chinese type2diabetic patients. Animal study suggested that the glucose metabolism was improved by n-3fatty acids via modulating insulin signaling pathway. The results of the present thesis may be important for the prevention and treatment of type2diabetes in the Chinese populations. |
