Role of lipid droplets and FITM2 in beta-cell physiology and pathophysiology
Hyperlipidemia is a known driving factor of T2DM, with saturated fatty acids (SFAs) pinpointed as the causation of β cell failure. Hence, intracellular handling of these SFAs, in β cells, was thought to be vital in preventing the loss of its function. The biogenesis of lipid droplets (LDs) forms an...
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| Format: | Thesis-Doctor of Philosophy |
| Language: | English |
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Nanyang Technological University
2022
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| Online Access: | https://hdl.handle.net/10356/158047 |
| _version_ | 1811677097749381120 |
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| author | Ho, Calvin Qing Wei |
| author2 | Yusuf Ali |
| author_facet | Yusuf Ali Ho, Calvin Qing Wei |
| author_sort | Ho, Calvin Qing Wei |
| collection | NTU |
| description | Hyperlipidemia is a known driving factor of T2DM, with saturated fatty acids (SFAs) pinpointed as the causation of β cell failure. Hence, intracellular handling of these SFAs, in β cells, was thought to be vital in preventing the loss of its function. The biogenesis of lipid droplets (LDs) forms an important arm of lipid handling as the ability to safely sequester these toxic fatty acids as neutral lipids would prevent the harmful effects of SFAs. In our study, we found that loss of FITM2, a protein essential of LD biogenesis, resulted in poor glycemic control β cell function in mice. Further delineation of SFA effects on FITM2 revealed an induction of degradation of FITM2 through S-palmitoylation and ERAD-C pathway. Lastly, every-other-day fasting (EODF) was shown to promote the stability of FITM2 and prevent SFA-induced lipotoxicity, hence suggesting the possibility of EODF as a potential therapeutic intervention for T2DM. |
| first_indexed | 2024-10-01T02:31:57Z |
| format | Thesis-Doctor of Philosophy |
| id | ntu-10356/158047 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:31:57Z |
| publishDate | 2022 |
| publisher | Nanyang Technological University |
| record_format | dspace |
| spelling | ntu-10356/1580472023-03-05T17:09:06Z Role of lipid droplets and FITM2 in beta-cell physiology and pathophysiology Ho, Calvin Qing Wei Yusuf Ali Lee Kong Chian School of Medicine (LKCMedicine) yusuf.ali@ntu.edu.sg Science::Medicine Hyperlipidemia is a known driving factor of T2DM, with saturated fatty acids (SFAs) pinpointed as the causation of β cell failure. Hence, intracellular handling of these SFAs, in β cells, was thought to be vital in preventing the loss of its function. The biogenesis of lipid droplets (LDs) forms an important arm of lipid handling as the ability to safely sequester these toxic fatty acids as neutral lipids would prevent the harmful effects of SFAs. In our study, we found that loss of FITM2, a protein essential of LD biogenesis, resulted in poor glycemic control β cell function in mice. Further delineation of SFA effects on FITM2 revealed an induction of degradation of FITM2 through S-palmitoylation and ERAD-C pathway. Lastly, every-other-day fasting (EODF) was shown to promote the stability of FITM2 and prevent SFA-induced lipotoxicity, hence suggesting the possibility of EODF as a potential therapeutic intervention for T2DM. Doctor of Philosophy 2022-05-16T10:51:10Z 2022-05-16T10:51:10Z 2022 Thesis-Doctor of Philosophy Ho, C. Q. W. (2022). Role of lipid droplets and FITM2 in beta-cell physiology and pathophysiology. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/158047 https://hdl.handle.net/10356/158047 10.32657/10356/158047 en MOE2015-T2-2-087 MOE2017-T1-001-220 MOE2019-T1-001-059 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University |
| spellingShingle | Science::Medicine Ho, Calvin Qing Wei Role of lipid droplets and FITM2 in beta-cell physiology and pathophysiology |
| title | Role of lipid droplets and FITM2 in beta-cell physiology and pathophysiology |
| title_full | Role of lipid droplets and FITM2 in beta-cell physiology and pathophysiology |
| title_fullStr | Role of lipid droplets and FITM2 in beta-cell physiology and pathophysiology |
| title_full_unstemmed | Role of lipid droplets and FITM2 in beta-cell physiology and pathophysiology |
| title_short | Role of lipid droplets and FITM2 in beta-cell physiology and pathophysiology |
| title_sort | role of lipid droplets and fitm2 in beta cell physiology and pathophysiology |
| topic | Science::Medicine |
| url | https://hdl.handle.net/10356/158047 |
| work_keys_str_mv | AT hocalvinqingwei roleoflipiddropletsandfitm2inbetacellphysiologyandpathophysiology |