The Study On Fatty Acids And Desaturase Activities And Their Associations With Central Obesity

Central obesity is a chronic condition with long-term energy imbalance. Diet as the major resource of energy for human being, is closely related to the development of central obesity. The quantity and quality of dietary intake could be assessed by plasma nutrient biomarkers and the adherence to a diet pattern. The plasma nutrient biomarkers depends on both dietary intake and the endogenous enzymes activity, thus could be used as objective indicator for diet intake. Dietary patterns are defined as the quantities, proportions, combinations and frequencies of different foods in diet. For example, the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) are the most popular diet patterns. According to 2010 American Dietary Guidelines, consideration of overall eating patterns can be more applicable for modification of dietary intake. Several studies suggested that plasma fatty acids and dietary patterns were associated with obesity and obesity-related chronic diseases. However, mixed results have been reported, and the research on central obesity is lacking.Except for environmental effect, the fatty acid composition was determined by endogenous enzyme activities which largely depend on genetic effect. By far, genome-wide association studies (GWAS) have identified dozens of single nucleotide polymorphisms (SNPs) which related to fatty acids desaturase activities. Several investigations demonstrated that these fatty acids-related SNPs associated with dyslipidemia. However, their associations with obesity or central obesity have not yet been investigated. Since the associations between fatty acids, cardiovascular risk factors and central obesity are complicated, it will provide new insight to the understanding of this triangle by exploring the genetic variation. Besides, it may provide the potential to protect against central obesity using personalized intervention based on individual’s genetic variation.This thesis includes the following aspects:1) To explore the cross-sectional and longitudinal association between plasma nutrient biomarkers and waist-to-height ratio (WHtR) in youth with type 1 diabetes; 2) To explore the associations between dietary patterns and WHtR in youth with type 1 diabetes; 3) To investigate the association of circulating omega-6 long-chain polyunsaturated fatty acids and desaturase activities with the risk of type 2 diabetes using meta-analysis; 4) To identify the relationship between fatty acids-related SNP and fat distribution and cardiovascular risk factors in Chinese adults.The main findings are summarized as followings:1. The plasma fatty acids and vitamins were associated with WHtR in youth with type 1 diabetes. The associations depended on participants’weight status. The most remarkable effect size was observed in obese group (defined by BMI). In obese participants, baseline stearic acid (SA, C18:0), dihomo-y-linolenic acid (DGLA, C20:3) and △6-desaturase activity (D6D) were associated with higher WHtR; while baseline oleic acid (OA, C18:1), A9-desaturase-18 activity (D9D-18) and vitamin D were associated with lower WHtR. In longitudinal analysis, baseline linoleic acid (LA, C18:2), omega-6/omega-3 ratio, vitamin D and vitamin E were associated with lower WHtR at follow-up only in obese participants.2. The DASH diet was associated with WHtR in youth with type 1 diabetes, more importantly, sex difference was observed. The significant negative association between DASH diet score and WHtR was observed only in male, which independent of energy intake, physical activity and BMI. No significant association was observed in female. Beside, the Mediterranean diet was not associated with WHtR in youth with type 1 diabetes.3. The circulating omega-6 polyunsaturated fatty acids associated with type 2 diabetes risk. A meta-analysis was conducted and found that the omega-6 fatty acid measured at different blood samples were associated with incident type 2 diabetes. The LA in serum (RR:0.92,95%CI:0.89,0.95), plasma (RR:0.82,95%CI:0.75,0.90) and erythrocyte (RR:0.88,95%CI:0.82,0.94) were associated with lower risk of type 2 diabetes. Blood arachidonic acid [AA (20:4)] was not associated with incident type 2 diabetes. The DGLA(20:3) in plasma (RR:1.41,95%CI:1.28,1.56) and erythrocyte (RR:1.11,95%CI:1.04,1.18) were associated with higher risk of type 2 diabetes. The D6D calculated by the ratio of fatty acids from plasma (RR:1.45,95%CI:1.31,1.62) and erythrocyte (RR:1.19,95%CI:1.12,1.26) were associated with higher risk of type 2 diabetes, while the plasma (RR:0.81,95%CI:0.75,0.88) and erythrocyte (RR:0.84, 95%CI:0.79,0.90) △5-desaturaseactivity (D5D) were associated with lower risk of type 2 diabetes.4. In Chinese adults, the fatty acids-related SNP associated with fat distribution and cardiovascular risk factors. More importantly, the age difference was observed. In women, the minor allele C of rsl74547 which located in FADSlgene was associated lower Android fat mass percent, after adjustment of Gynoid fat mass percent and other confounders. In men, the C allele of rs 174547 was associated with lower Gynoid fat mass percent, after adjustment of Android fat mass percent and others. In women, the C allele was associated with lower low density lipoprotein-cholesterol; while in men, the C allele was associated with higher systolic blood pressure and triglyceride.In conclusion, the present study investigated the associations between fatty acids and central obesity and cardiovascular risk factors from multiple aspects. We demonstrated that the genetic variation, fatty acids biomarker and fatty acids intake were closely related to central obesity, although these findings should be further confirmed in other populations. With the development of society, the obesity has become a worldwide public health problem. Using personalized nutritional therapy to protect against central obesity could be a cost-effective way and may be of important public health significance.