Physiological consequences of Aldolase C deficiency during lactation.
The lactating mammary gland strongly induces de novo lipogenesis (DNL) to support the synthesis of fatty acids, triglycerides, and cholesterol found within milk. In monogastric species, glucose is a major substrate utilized for DNL within the lactating mammary gland and must be efficiently taken up...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2024-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0315719 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841555369428516864 |
|---|---|
| author | James A Votava Jing Fan Brian W Parks |
| author_facet | James A Votava Jing Fan Brian W Parks |
| author_sort | James A Votava |
| collection | DOAJ |
| description | The lactating mammary gland strongly induces de novo lipogenesis (DNL) to support the synthesis of fatty acids, triglycerides, and cholesterol found within milk. In monogastric species, glucose is a major substrate utilized for DNL within the lactating mammary gland and must be efficiently taken up and processed to supply cytosolic acetyl-CoA for DNL. Along with the enzymes of the DNL pathway, the glycolytic enzyme, Aldolase C (Aldoc), is transcriptionally upregulated and is highly expressed during lactation in the mammary gland, suggesting a role for Aldoc in lactation. Aldoc is also a transcriptional target of the sterol regulatory element binding proteins 1 and 2 (Srebp1 and Srebp2), which transcriptionally regulate enzymes within the DNL pathway and has recently been shown to regulate plasma cholesterol and triglycerides. Here, we investigate the role of Aldoc in lactation, by utilizing a whole-body Aldoc knockout mouse. Our results demonstrate that Aldoc has a significant impact on lactation, whereby pups nursing from Aldoc-/- dams have reduced body weight. Biochemical analysis of milk identified that milk from Aldoc-/- dams have significantly higher galactose, lower lactose, and cholesterol content. Mass spectrometry analysis of milk lipids from Aldoc-/- dams revealed significantly lower quantities of medium and long chain fatty acid containing triglycerides, which has direct implications on lactation as these are the predominant triglycerides synthesized from glucose in human mammary gland. Overall, our results provide functional evidence for the contribution of Aldoc in mammary gland lactose and lipid synthesis during lactation. |
| format | Article |
| id | doaj-art-237c3c20929a4b139fca7014c98b31ad |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-237c3c20929a4b139fca7014c98b31ad2025-01-08T05:33:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e031571910.1371/journal.pone.0315719Physiological consequences of Aldolase C deficiency during lactation.James A VotavaJing FanBrian W ParksThe lactating mammary gland strongly induces de novo lipogenesis (DNL) to support the synthesis of fatty acids, triglycerides, and cholesterol found within milk. In monogastric species, glucose is a major substrate utilized for DNL within the lactating mammary gland and must be efficiently taken up and processed to supply cytosolic acetyl-CoA for DNL. Along with the enzymes of the DNL pathway, the glycolytic enzyme, Aldolase C (Aldoc), is transcriptionally upregulated and is highly expressed during lactation in the mammary gland, suggesting a role for Aldoc in lactation. Aldoc is also a transcriptional target of the sterol regulatory element binding proteins 1 and 2 (Srebp1 and Srebp2), which transcriptionally regulate enzymes within the DNL pathway and has recently been shown to regulate plasma cholesterol and triglycerides. Here, we investigate the role of Aldoc in lactation, by utilizing a whole-body Aldoc knockout mouse. Our results demonstrate that Aldoc has a significant impact on lactation, whereby pups nursing from Aldoc-/- dams have reduced body weight. Biochemical analysis of milk identified that milk from Aldoc-/- dams have significantly higher galactose, lower lactose, and cholesterol content. Mass spectrometry analysis of milk lipids from Aldoc-/- dams revealed significantly lower quantities of medium and long chain fatty acid containing triglycerides, which has direct implications on lactation as these are the predominant triglycerides synthesized from glucose in human mammary gland. Overall, our results provide functional evidence for the contribution of Aldoc in mammary gland lactose and lipid synthesis during lactation.https://doi.org/10.1371/journal.pone.0315719 |
| spellingShingle | James A Votava Jing Fan Brian W Parks Physiological consequences of Aldolase C deficiency during lactation. PLoS ONE |
| title | Physiological consequences of Aldolase C deficiency during lactation. |
| title_full | Physiological consequences of Aldolase C deficiency during lactation. |
| title_fullStr | Physiological consequences of Aldolase C deficiency during lactation. |
| title_full_unstemmed | Physiological consequences of Aldolase C deficiency during lactation. |
| title_short | Physiological consequences of Aldolase C deficiency during lactation. |
| title_sort | physiological consequences of aldolase c deficiency during lactation |
| url | https://doi.org/10.1371/journal.pone.0315719 |
| work_keys_str_mv | AT jamesavotava physiologicalconsequencesofaldolasecdeficiencyduringlactation AT jingfan physiologicalconsequencesofaldolasecdeficiencyduringlactation AT brianwparks physiologicalconsequencesofaldolasecdeficiencyduringlactation |