Differential regulation of sphingolipid metabolism in plasma, hippocampus and cerebral cortex of mice administered sphingolipid modulating agents
Accumulation of ceramide is implicated in mediating the cellular responses to stress and aberrant sphingolipid metabolism is frequently associated with metabolic and neurodegenerative diseases. It is often assumed that (1) peripheral disturbances in sphingolipid concentrations are reflective of proc...
| Main Authors: | , , , , , |
|---|---|
| Format: | Journal Article |
| Published: |
Wiley-Blackwell Publishing Ltd.
2017
|
| Online Access: | http://hdl.handle.net/20.500.11937/51196 |
| _version_ | 1848758638287519744 |
|---|---|
| author | Giles, Corey Takechi, Ryu Mellett, N. Meikle, P. Dhaliwal, Satvinder Mamo, John |
| author_facet | Giles, Corey Takechi, Ryu Mellett, N. Meikle, P. Dhaliwal, Satvinder Mamo, John |
| author_sort | Giles, Corey |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Accumulation of ceramide is implicated in mediating the cellular responses to stress and aberrant sphingolipid metabolism is frequently associated with metabolic and neurodegenerative diseases. It is often assumed that (1) peripheral disturbances in sphingolipid concentrations are reflective of processes occurring in the brain, or (2) circulating sphingolipids directly influence cerebral sphingolipid abundance. In order to address these assumptions, this study explores, in a physiological system, the metabolic pathways regulating sphingolipid metabolism in the brain and plasma of mice. Male C57Bl/6 were maintained on a low fat (CTRL) or saturated fat enriched (SFA) diet with, or without the provision of sphingolipid modulating agents. Following six months of feeding, the abundance of seven sphingolipid classes was assessed by LC-ESI-MS/MS in the hippocampus (HPF), cerebral cortex (CTX) and plasma. Long-term consumption of the SFA diet increased ceramide and dihydroceramide in the plasma. Inhibiting de novo synthesis ameliorated this effect, while inhibition of acidic sphingomyelinase, or the sphingosine-1-phosphate receptor agonist did not. SFA feeding did not influence sphingolipid levels in either the HPF or CTX. De novo synthesis inhibition reduced ceramide in the CTX, whilst treatment with a sphingosine-1-phosphate receptor agonist reduced ceramides in the HPF. Analysis of the individual ceramide species revealed the effects were chain-length dependent. Both positive and negative correlations were observed between plasma and HPF/CTX ceramide species. The findings in this study show that HPF and CTX sphingolipid concentration are influenced by distinct pathways, independent of peripheral sphingolipid concentration. This article is protected by copyright. All rights reserved. |
| first_indexed | 2025-11-14T09:47:10Z |
| format | Journal Article |
| id | curtin-20.500.11937-51196 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:47:10Z |
| publishDate | 2017 |
| publisher | Wiley-Blackwell Publishing Ltd. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-511962017-09-13T15:36:21Z Differential regulation of sphingolipid metabolism in plasma, hippocampus and cerebral cortex of mice administered sphingolipid modulating agents Giles, Corey Takechi, Ryu Mellett, N. Meikle, P. Dhaliwal, Satvinder Mamo, John Accumulation of ceramide is implicated in mediating the cellular responses to stress and aberrant sphingolipid metabolism is frequently associated with metabolic and neurodegenerative diseases. It is often assumed that (1) peripheral disturbances in sphingolipid concentrations are reflective of processes occurring in the brain, or (2) circulating sphingolipids directly influence cerebral sphingolipid abundance. In order to address these assumptions, this study explores, in a physiological system, the metabolic pathways regulating sphingolipid metabolism in the brain and plasma of mice. Male C57Bl/6 were maintained on a low fat (CTRL) or saturated fat enriched (SFA) diet with, or without the provision of sphingolipid modulating agents. Following six months of feeding, the abundance of seven sphingolipid classes was assessed by LC-ESI-MS/MS in the hippocampus (HPF), cerebral cortex (CTX) and plasma. Long-term consumption of the SFA diet increased ceramide and dihydroceramide in the plasma. Inhibiting de novo synthesis ameliorated this effect, while inhibition of acidic sphingomyelinase, or the sphingosine-1-phosphate receptor agonist did not. SFA feeding did not influence sphingolipid levels in either the HPF or CTX. De novo synthesis inhibition reduced ceramide in the CTX, whilst treatment with a sphingosine-1-phosphate receptor agonist reduced ceramides in the HPF. Analysis of the individual ceramide species revealed the effects were chain-length dependent. Both positive and negative correlations were observed between plasma and HPF/CTX ceramide species. The findings in this study show that HPF and CTX sphingolipid concentration are influenced by distinct pathways, independent of peripheral sphingolipid concentration. This article is protected by copyright. All rights reserved. 2017 Journal Article http://hdl.handle.net/20.500.11937/51196 10.1111/jnc.13964 Wiley-Blackwell Publishing Ltd. restricted |
| spellingShingle | Giles, Corey Takechi, Ryu Mellett, N. Meikle, P. Dhaliwal, Satvinder Mamo, John Differential regulation of sphingolipid metabolism in plasma, hippocampus and cerebral cortex of mice administered sphingolipid modulating agents |
| title | Differential regulation of sphingolipid metabolism in plasma, hippocampus and cerebral cortex of mice administered sphingolipid modulating agents |
| title_full | Differential regulation of sphingolipid metabolism in plasma, hippocampus and cerebral cortex of mice administered sphingolipid modulating agents |
| title_fullStr | Differential regulation of sphingolipid metabolism in plasma, hippocampus and cerebral cortex of mice administered sphingolipid modulating agents |
| title_full_unstemmed | Differential regulation of sphingolipid metabolism in plasma, hippocampus and cerebral cortex of mice administered sphingolipid modulating agents |
| title_short | Differential regulation of sphingolipid metabolism in plasma, hippocampus and cerebral cortex of mice administered sphingolipid modulating agents |
| title_sort | differential regulation of sphingolipid metabolism in plasma, hippocampus and cerebral cortex of mice administered sphingolipid modulating agents |
| url | http://hdl.handle.net/20.500.11937/51196 |