| 1. |
- Gopalacharyulu, Peddinti V., et al.
(författare)
-
Dynamic network topology changes in functional modules predict responses to oxidative stress in yeast
- 2009
-
Ingår i: Molecular Biosystems. - : Royal Society of Chemistry. - 1742-206X .- 1742-2051. ; 5:3, s. 276-287
-
Tidskriftsartikel (refereegranskat)abstract
- In response to environmental challenges, biological systems respond with dynamic adaptive changes in order to maintain the functionality of the system. Such adaptations may lead to cumulative stress over time, possibly leading to global failure of the system. When studying such systems responses, it is therefore important to understand them in system-wide and dynamic context. Here we hypothesize that dynamic changes in the topology of functional modules of integrated biological networks reflect their activity under specific environmental challenges. We introduce topological enrichment analysis of functional subnetworks (TEAFS), a method for the analysis of integrated molecular profile and interactome data, which we validated by comprehensive metabolomic analysis of dynamic yeast response under oxidative stress. TEAFS identified activation of multiple stress response related mechanisms, such as lipid metabolism and phospholipid biosynthesis. We identified, among others, a fatty acid elongase IFA38 as a hub protein which was absent at all time points under oxidative stress conditions. The deletion mutant of the IFA38 encoding gene is known for the accumulation of ceramides. By applying a comprehensive metabolomic analysis, we confirmed the increased concentrations over time of ceramides and palmitic acid, a precursor of de novo ceramide biosynthesis. Our results imply that the connectivity of the system is being dynamically modulated in response to oxidative stress, progressively leading to the accumulation of (lipo)toxic lipids such as ceramides. Studies of local network topology dynamics can be used to investigate as well as predict the activity of biological processes and the system's responses to environmental challenges and interventions.
|
|
| 2. |
- Velagapudi, Vidya R., et al.
(författare)
-
The gut microbiota modulates host energy and lipid metabolism in mice
- 2009
-
Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 51:5, s. 1101-1112
-
Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota has recently been identified as an environmental factor that may promote metabolic diseases. To investigate the effect of gut microbiota on host energy and lipid metabolism, we compared the serum metabolome and the lipidomes of serum, adipose tissue, and liver of conventionally raised (CONV-R) and germ-free mice. The serum metabolome of CONV-R mice was characterized by increased levels of energy metabolites e.g. pyruvic acid, citric acid, fumaric acid, and malic acid while levels of cholesterol and fatty acids were reduced. We also showed that the microbiota modified a number of lipid species in the serum, adipose tissue and liver, with its greatest effect on triglyceride and phosphatidylcholine species. Triglyceride levels were lower in serum but higher in adipose tissue and liver of CONV-R mice, consistent with increased lipid clearance. Our findings show that the gut microbiota affects both host energy and lipid metabolism, and highlights its role in the development of metabolic diseases.
|
|
