ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse model
AimWe evaluated a novel treatment for obesity-related renal, an ATP-citrate lyase (ACL) inhibitor, to attenuate ectopic lipid accumulation (ELA) in the kidney and the ensuing inflammation.Materials and methodsAn ACL inhibitor was administered intragastrically to 12-week-old db/db mice for 30 days. T...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-12-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.914865/full |
| _version_ | 1811177998371520512 |
|---|---|
| author | Zishun Zhan Zishun Zhan Aimei Li Aimei Li Wei Zhang Wei Zhang Xueqin Wu Xueqin Wu Jinrong He Jinrong He Zhi Li Zhi Li Yanchun Li Jian Sun Jian Sun Jian Sun Hao Zhang Hao Zhang |
| author_facet | Zishun Zhan Zishun Zhan Aimei Li Aimei Li Wei Zhang Wei Zhang Xueqin Wu Xueqin Wu Jinrong He Jinrong He Zhi Li Zhi Li Yanchun Li Jian Sun Jian Sun Jian Sun Hao Zhang Hao Zhang |
| author_sort | Zishun Zhan |
| collection | DOAJ |
| description | AimWe evaluated a novel treatment for obesity-related renal, an ATP-citrate lyase (ACL) inhibitor, to attenuate ectopic lipid accumulation (ELA) in the kidney and the ensuing inflammation.Materials and methodsAn ACL inhibitor was administered intragastrically to 12-week-old db/db mice for 30 days. The appearance of ELA was observed by staining kidney sections with Oil Red O, and the differences in tissue lipid metabolites were assessed by mass spectrometry. The anti-obesity and renoprotection effects of ACL inhibitors were observed by histological examination and multiple biochemical assays.ResultsUsing the AutoDock Vina application, we determined that among the four known ACL inhibitors (SB-204990, ETC-1002, NDI-091143, and BMS-303141), BMS-303141 had the highest affinity for ACL and reduced ACL expression in the kidneys of db/db mice. We reported that BMS-303141 administration could decrease the levels of serum lipid and renal lipogenic enzymes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), HMG-CoA reductase (HMGCR), and diminish renal ELA in db/db mice. In addition, we found that reducing ELA improved renal injuries, inflammation, and tubulointerstitial fibrosis.ConclusionACL inhibitor BMS-303141 protects against obesity-related renal injuries. |
| first_indexed | 2024-04-11T06:12:00Z |
| format | Article |
| id | doaj.art-6e9c4f5e30eb4f248730a4dddb8b57a9 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-11T06:12:00Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-6e9c4f5e30eb4f248730a4dddb8b57a92022-12-22T04:41:14ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-12-011310.3389/fendo.2022.914865914865ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse modelZishun Zhan0Zishun Zhan1Aimei Li2Aimei Li3Wei Zhang4Wei Zhang5Xueqin Wu6Xueqin Wu7Jinrong He8Jinrong He9Zhi Li10Zhi Li11Yanchun Li12Jian Sun13Jian Sun14Jian Sun15Hao Zhang16Hao Zhang17Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaThe Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, ChinaDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaThe Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, ChinaDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaThe Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, ChinaDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaThe Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, ChinaDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaThe Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, ChinaDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaThe Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, ChinaDivision of Biological Sciences, Department of Medicine, University of Chicago, Chicago, Chicago, IL, United StatesDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaThe Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, ChinaDepartment of Rheumatology and Immunology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaThe Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, ChinaAimWe evaluated a novel treatment for obesity-related renal, an ATP-citrate lyase (ACL) inhibitor, to attenuate ectopic lipid accumulation (ELA) in the kidney and the ensuing inflammation.Materials and methodsAn ACL inhibitor was administered intragastrically to 12-week-old db/db mice for 30 days. The appearance of ELA was observed by staining kidney sections with Oil Red O, and the differences in tissue lipid metabolites were assessed by mass spectrometry. The anti-obesity and renoprotection effects of ACL inhibitors were observed by histological examination and multiple biochemical assays.ResultsUsing the AutoDock Vina application, we determined that among the four known ACL inhibitors (SB-204990, ETC-1002, NDI-091143, and BMS-303141), BMS-303141 had the highest affinity for ACL and reduced ACL expression in the kidneys of db/db mice. We reported that BMS-303141 administration could decrease the levels of serum lipid and renal lipogenic enzymes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), HMG-CoA reductase (HMGCR), and diminish renal ELA in db/db mice. In addition, we found that reducing ELA improved renal injuries, inflammation, and tubulointerstitial fibrosis.ConclusionACL inhibitor BMS-303141 protects against obesity-related renal injuries.https://www.frontiersin.org/articles/10.3389/fendo.2022.914865/fullBMS-303141ACLATP-citrate lyaseectopic lipid accumulationrenal inflammationobesity-related nephropathy |
| spellingShingle | Zishun Zhan Zishun Zhan Aimei Li Aimei Li Wei Zhang Wei Zhang Xueqin Wu Xueqin Wu Jinrong He Jinrong He Zhi Li Zhi Li Yanchun Li Jian Sun Jian Sun Jian Sun Hao Zhang Hao Zhang ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse model Frontiers in Endocrinology BMS-303141 ACL ATP-citrate lyase ectopic lipid accumulation renal inflammation obesity-related nephropathy |
| title | ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse model |
| title_full | ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse model |
| title_fullStr | ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse model |
| title_full_unstemmed | ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse model |
| title_short | ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse model |
| title_sort | atp citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db db mouse model |
| topic | BMS-303141 ACL ATP-citrate lyase ectopic lipid accumulation renal inflammation obesity-related nephropathy |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.914865/full |
| work_keys_str_mv | AT zishunzhan atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT zishunzhan atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT aimeili atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT aimeili atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT weizhang atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT weizhang atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT xueqinwu atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT xueqinwu atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT jinronghe atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT jinronghe atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT zhili atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT zhili atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT yanchunli atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT jiansun atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT jiansun atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT jiansun atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT haozhang atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel AT haozhang atpcitratelyaseinhibitorimprovesectopiclipidaccumulationinthekidneyinadbdbmousemodel |