Feeding Angptl4 −/− mice trans fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites
Angiopoietin-like 4 (ANGPTL4) regulates plasma triglyceride levels by inhibiting LPL. Inactivation of ANGPTL4 decreases plasma triglycerides and reduces the risk of coronary artery disease. Unfortunately, targeting ANGPTL4 for the therapeutic management of dyslipidemia and atherosclerosis is hampere...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2018
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| Online Access: | https://hdl.handle.net/10356/87195 http://hdl.handle.net/10220/44365 |
| _version_ | 1826117623965810688 |
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| author | Oteng, Antwi-Boasiako Bhattacharya, Asmita Brodesser, Susanne Qi, Ling Tan, Nguan Soon Kersten, Sander |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Oteng, Antwi-Boasiako Bhattacharya, Asmita Brodesser, Susanne Qi, Ling Tan, Nguan Soon Kersten, Sander |
| author_sort | Oteng, Antwi-Boasiako |
| collection | NTU |
| description | Angiopoietin-like 4 (ANGPTL4) regulates plasma triglyceride levels by inhibiting LPL. Inactivation of ANGPTL4 decreases plasma triglycerides and reduces the risk of coronary artery disease. Unfortunately, targeting ANGPTL4 for the therapeutic management of dyslipidemia and atherosclerosis is hampered by the observation that mice and monkeys in which ANGPTL4 is inactivated exhibit lipid accumulation in the mesenteric lymph nodes (MLNs). In mice these pathological events exclusively unfold upon feeding a high saturated FA diet and are followed by an ultimately lethal pro-inflammatory response and chylous ascites. Here, we show that Angptl4−/− mice fed a diet rich in trans FAs develop numerous lipid-filled giant cells in their MLNs, yet do not have elevated serum amyloid and haptoglobin, do not exhibit ascites, and survive, unlike Angptl4−/− mice fed a saturated FA-rich diet. In RAW264.7 macrophages, the saturated FA, palmitate, markedly increased markers of inflammation and the unfolded protein response, whereas the trans-unsaturated elaidate and the cis-unsaturated oleate had the opposite effect. In conclusion, trans and saturated FAs have very distinct biological effects in macrophages. Furthermore, lipid accumulation in MLNs is uncoupled from activation of an acute-phase response and chylous ascites, suggesting that ANGPTL4 should not be fully dismissed as target for dyslipidemia. |
| first_indexed | 2024-10-01T04:30:40Z |
| format | Journal Article |
| id | ntu-10356/87195 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:30:40Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/871952020-11-01T05:18:14Z Feeding Angptl4 −/− mice trans fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites Oteng, Antwi-Boasiako Bhattacharya, Asmita Brodesser, Susanne Qi, Ling Tan, Nguan Soon Kersten, Sander Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences Inflammation Lipotoxicity Angiopoietin-like 4 (ANGPTL4) regulates plasma triglyceride levels by inhibiting LPL. Inactivation of ANGPTL4 decreases plasma triglycerides and reduces the risk of coronary artery disease. Unfortunately, targeting ANGPTL4 for the therapeutic management of dyslipidemia and atherosclerosis is hampered by the observation that mice and monkeys in which ANGPTL4 is inactivated exhibit lipid accumulation in the mesenteric lymph nodes (MLNs). In mice these pathological events exclusively unfold upon feeding a high saturated FA diet and are followed by an ultimately lethal pro-inflammatory response and chylous ascites. Here, we show that Angptl4−/− mice fed a diet rich in trans FAs develop numerous lipid-filled giant cells in their MLNs, yet do not have elevated serum amyloid and haptoglobin, do not exhibit ascites, and survive, unlike Angptl4−/− mice fed a saturated FA-rich diet. In RAW264.7 macrophages, the saturated FA, palmitate, markedly increased markers of inflammation and the unfolded protein response, whereas the trans-unsaturated elaidate and the cis-unsaturated oleate had the opposite effect. In conclusion, trans and saturated FAs have very distinct biological effects in macrophages. Furthermore, lipid accumulation in MLNs is uncoupled from activation of an acute-phase response and chylous ascites, suggesting that ANGPTL4 should not be fully dismissed as target for dyslipidemia. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2018-02-01T04:50:21Z 2019-12-06T16:37:00Z 2018-02-01T04:50:21Z 2019-12-06T16:37:00Z 2017 Journal Article Oteng, A.-B., Bhattacharya, A., Brodesser, S., Qi, L., Tan, N. S., & Kersten, S. (2017). Feeding Angptl4 −/− mice trans fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites. Journal of Lipid Research, 58(6), 1100-1113. https://hdl.handle.net/10356/87195 http://hdl.handle.net/10220/44365 10.1194/jlr.M074278 en Journal of Lipid Research © 2017 American Society for Biochemistry and Molecular Biology (ASBMB). This paper was published in Journal of Lipid Research and is made available as an electronic reprint (preprint) with permission of American Society for Biochemistry and Molecular Biology (ASBMB). The published version is available at: [http://dx.doi.org/10.1194/jlr.M074278]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. 14 p. application/pdf |
| spellingShingle | Inflammation Lipotoxicity Oteng, Antwi-Boasiako Bhattacharya, Asmita Brodesser, Susanne Qi, Ling Tan, Nguan Soon Kersten, Sander Feeding Angptl4 −/− mice trans fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites |
| title | Feeding
Angptl4
−/−
mice
trans
fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites |
| title_full | Feeding
Angptl4
−/−
mice
trans
fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites |
| title_fullStr | Feeding
Angptl4
−/−
mice
trans
fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites |
| title_full_unstemmed | Feeding
Angptl4
−/−
mice
trans
fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites |
| title_short | Feeding
Angptl4
−/−
mice
trans
fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites |
| title_sort | feeding angptl4 mice trans fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites |
| topic | Inflammation Lipotoxicity |
| url | https://hdl.handle.net/10356/87195 http://hdl.handle.net/10220/44365 |
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