| 1. |
- Haslam, Danielle E., et al.
(författare)
-
Changes in metabolites during an oral glucose tolerance test in early and mid-pregnancy : Findings from the PEARLS randomized, controlled lifestyle trial
- 2020
-
Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 10:7
-
Tidskriftsartikel (refereegranskat)abstract
- The oral glucose tolerance test (OGTT) is used to diagnose gestational and other types of diabetes. We examined metabolite changes during an OGTT, and how a comprehensive diet and physical activity intervention may influence these changes in a population of overweight/obese Hispanic pregnant women. Integration of changes in metabolites during an OGTT may help us gain preliminary insights into how glucose metabolism changes during pregnancy. Among women from the Pregnancy and EARly Lifestyle improvement Study (PEARLS), we measured metabolites during a multipoint OGTT (fasting, 30, 60 and 120 min) at early and mid-pregnancy. Metabolite levels were measured by liquid chromatography–mass spectrometry in plasma samples in the lifestyle intervention (n = 13) and control (n = 16) arms of the study. A total of 65 candidate metabolites were selected that displayed changes during an OGTT in previous studies. Paired and unpaired t-tests were used to examine differences in ∆fast-120 min: (1) at early and mid-pregnancy; and (2) by intervention assignment. We applied principal component analysis (PCA) to identify those metabolites that differed by intervention assignment and OGTT time points. Most of the characteristic changes in metabolites post-OGTT were similar at both gestational time points. PCA identified characteristic metabolite patterns associated with OGTT time points at both early and mid-pregnancy. These metabolites included ketone bodies, tryptophan, acyl carnitines, polyunsaturated fatty acids, and biomarkers related to bile acid, urea cycle, arginine, and proline metabolism. PCA identified distinct ∆fast-120 min in fatty acid, acyl carnitine, bile acid, ketone body, and amino acid levels at mid-compared to early pregnancy. Participants in the intervention group did not display mean decreases in ∆fast-120 min of several long-chain acyl carnitines that were observed in the control group. These findings provide preliminary insight into metabolites, whose role in increased insulin resistance during pregnancy, should be explored further in future studies.
|
|
| 2. |
- Hou, Jianshen, et al.
(författare)
-
Rewiring carbon flux in Escherichia coli using a bifunctional molecular switch
- 2020
-
Ingår i: Metabolic Engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 61, s. 47-57
-
Tidskriftsartikel (refereegranskat)abstract
- The unbalanced distribution of carbon flux in microbial cell factories can lead to inefficient production and poor cell growth. Uncoupling cell growth and chemical synthesis can therefore improve microbial cell factory efficiency. Such uncoupling, which requires precise manipulation of carbon fluxes, can be achieved by up-regulating or down-regulating the expression of enzymes of various pathways. In this study, a dynamic turn-off switch (dTFS) and a dynamic turn-on switch (dTNS) were constructed using growth phase-dependent promoters and degrons. By combining the dTFS and dTNS, a bifunctional molecular switch that could orthogonally regulate two target proteins was introduced. This bifunctional molecular switch was used to uncouple cell growth from shikimic acid and D-glucaric acid synthesis, resulting in the production of 14.33 g/L shikimic acid and the highest reported productivity of D-glucaric acid (0.0325 g/L/h) in Escherichia coli MG1655. This proved that the bifunctional molecular switch could rewire carbon fluxes by controlling target protein abundance.
|
|
