Dietary tryptophan and the risk of obesity and type 2 diabetes: Total effect and mediation effect of sleep duration.

OBJECTIVE: The aims of this study were to examine the effects of tryptophan consumption on obesity and type 2 diabetes (T2D) risk and whether sleep duration mediates these effects. METHODS: Overall, data of 7,908 participants were obtained from the China Health and Nutrition Survey (1997-2011). A total of 6,373 and 4,398 participants who reported sleep duration and had blood samples, respectively, were incorporated into subgroup analyses. Multivariate Cox regression models were used to assess the associations between tertiles of tryptophan intake with obesity and T2D. General linear regression models were used to evaluate the effect of tryptophan on sleep time and plasma biomarkers. RESULTS: Dietary tryptophan was significantly associated with decreased risk of obesity and T2D risk (hazard ratio tertile 3 to tertile 1 : 0.602 [95% CI: 0.500-0.724]; 0.693 [95% CI: 0.565-0.850]). Sleep duration was significantly higher, and hemoglobin A1c, total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B-100 (APO-B) were lower in the high tertile of tryptophan compared with the low tertile (p < 0.05). In addition, mediation effects on the associations of tryptophan intake with obesity and T2D risk were observed for sleep duration (estimated mediation percentage: 31.902% and 37.391%). CONCLUSIONS: Dietary tryptophan showed advantageous effects on obesity and T2D risk. Furthermore, sleep duration potentially mediated for these effects.

Folic acid oversupplementation during pregnancy disorders lipid metabolism in male offspring via regulating arginase 1-associated NOS3-AMPKα pathway.

BACKGROUND & AIMS: Folic acid supplementation is widely accepted during pregnancy, as it exerts a protective effect on neural tube defects. However, the long-term underlying effects of folic acid supplementation during pregnancy (FASDP) on offspring remain unclear. METHODS: Thirty pregnant female rats were randomly divided into normal control group, folic acid appropriate supplementation group (2.5 × FA group) and folic acid oversupplementation group (5 × FA group) and fed with corresponding folic acid concentration AIN93G diet. UPLC-Q-TOF-MS, UPLC-TQ-MS and GC-MS were performed to detect the serum metabolites profiles in adult male offspring and explore the effects of FASDP. Moreover, molecular biology technologies were used to clarify the underlying mechanism. RESULTS: We demonstrate that 2.5-folds folic acid leads to dyslipidemic-diabetic slightly in male offspring, while 5-folds folic acid aggravates the disorder and prominent hepatic lipid accumulations. Using untargeted and targeted metabolomics, total 63 differential metabolites and 12 significantly differential KEGG pathways are identified. Of note, arginine biosynthesis, arginine and proline metabolism are the two most significant pathways. Mechanistic investigations reveal that the increased levels of arginase-1 (Arg1) causes the lipid metabolism disorder by regulating nitric oxide synthase-3 (NOS3)-adenosine monophosphate activated protein kinase-α (AMPKα) pathway, resulting in lipid accumulation in hepatocytes. CONCLUSIONS: Our data suggest that maternal folic acid oversupplementation during pregnancy contributes to lipid metabolism disorder in male offspring by regulating Arg1-NOS3-AMPKα pathway.

Genetic predisposition to impaired metabolism of the branched chain amino acids, dietary intakes, and risk of type 2 diabetes.

BACKGROUND AND OBJECTIVES: Circulating branched chain amino acids (BCAAs) increase the risk of type 2 diabetes (T2D). The genetic variants in the BCAA metabolic pathway influence the individual metabolic ability of BCAAs and may affect circulating BCAA levels together with dietary intakes. So, we investigated whether genetic predisposition to impaired BCAA metabolism interacts with dietary BCAA intakes on the risk of type 2 diabetes and related parameters. METHODS: We estimated dietary BCAA intakes among 434 incident T2D cases and 434 age-matched controls from The Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases. The genetic risk score (GRS) was calculated on the basis of 5 variants having been identified in the BCAA metabolic pathway. Multivariate logistic regression models and general linear regression models were used to assess the interaction between dietary BCAAs and GRS on T2D risk and HbA1c. RESULTS: Dietary BCAAs significantly interact with metabolism related GRS on T2D risk and HbA1c (p for interaction = 0.038 and 0.015, respectively). A high intake of dietary BCAAs was positively associated with diabetes incidence only among high GRS (OR 2.40, 95% CI 1.39, 4.12, P for trend = 0.002). Dietary BCAAs were associated with 0.14% elevated HbA1c (p = 0.003) and this effect increased to 0.21% in high GRS (p = 0.003). Furthermore, GRS were associated with 9.19 µmol/L higher plasma BCAA levels (p = 0.006, P for interaction = 0.015) only among the highest BCAA intake individuals. CONCLUSIONS: Our study suggests that genetic predisposition to BCAA metabolism disorder modifies the effect of dietary BCAA intakes on T2D risk as well as HbA1c and that higher BCAA intakes exert an unfavorable effect on type 2 diabetes risk and HbA1c only among those with high genetic susceptibility.

Evaluation of liver tissue extraction protocol for untargeted metabolomics analysis by ultra-high-performance liquid chromatography/tandem mass spectrometry.

The aim of the untargeted metabolomics study is to obtain a global metabolome coverage from biological samples. Therefore, a comprehensive and systematic protocol for tissue metabolite extraction is highly desirable. In this study, we evaluated a comprehensive liver pretreatment strategy based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to obtain more metabolites using four different protocols. These protocols included (A) methanol protein precipitation, (B) two-step extraction of dichloromethane-methanol followed by methanol-water, (C) two-step extraction of methyl tert-butyl ether-methanol followed by methanol-water, and (D) two-step extraction of isopropanol-methanol followed by methanol-water. Our results showed that protocol D was superior to the others due to more extracted features, annotated metabolites, and better reproducibility. And then, the stability and extraction sequence of protocol D were evaluated. The results showed that extraction with isopropanol-methanol followed by methanol-water was the optimum preparation sequence, which offered higher extraction efficiency, satisfactory repeatability, and acceptable stability. Furthermore, the optimal protocol was successfully applied by liver samples of rats after high-fat intervention. In summary, our protocol enabled a comprehensive and systematic evaluation of liver pretreatment to obtain more medium-polar and nonpolar metabolites and was suitable for high-throughput metabolomics analysis.