DataVXAdvanced SciencePaper
journal article·2024-03Open access

LncRNA LINK‐A Remodels Tissue Inflammatory Microenvironments to Promote Obesity

Yu Chen, Hui Chen, Ying Wang, Fangzhou Liu, Xiao Fan, Chengyu Shi, Xinwan Su, Manman Tan, Yebin Yang, Bangxing Lin, Kai Lei, Lei Qu, Jiecheng Yang, Zhipeng Zhu, Zengzhuang Yuan, Shanshan Xie, Qinming Sun, Dante Neculai, Wei Liu, Qingfeng Yan, Xiang Wang, Jianzhong Shao, Jian Liu, Aifu Lin

Advanced Science· Volume 11· Issue 10
Publisher pageOpen full text
Source abstract

Abstract

Abstract High‐fat diet (HFD)‐induced obesity is a crucial risk factor for metabolic syndrome, mainly due to adipose tissue dysfunctions associated with it. However, the underlying mechanism remains unclear. This study has used genetic screening to identify an obesity‐associated human lncRNA LINK‐A as a critical molecule bridging the metabolic microenvironment and energy expenditure in vivo by establishing the HFD‐induced obesity knock‐in (KI) mouse model. Mechanistically, HFD LINK‐A KI mice induce the infiltration of inflammatory factors, including IL‐1β and CXCL16, through the LINK‐A/HB‐EGF/HIF1α feedback loop axis in a self‐amplified manner, thereby promoting the adipose tissue microenvironment remodeling and adaptive thermogenesis disorder, ultimately leading to obesity and insulin resistance. Notably, LINK‐A expression is positively correlated with inflammatory factor expression in individuals who are overweight. Of note, targeting LINK‐A via nucleic acid drug antisense oligonucleotides (ASO) attenuate HFD‐induced obesity and metabolic syndrome, pointing out LINK‐A as a valuable and effective therapeutic target for treating HFD‐induced obesity. Briefly, the results reveale the roles of lncRNAs (such as LINK‐A) in remodeling tissue inflammatory microenvironments to promote HFD‐induced obesity.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Cancer-related molecular mechanisms research · Lipid metabolism and disorders · Adipokines, Inflammation, and Metabolic Diseases

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

MOE Laboratory of Biosystem Homeostasis and Protection College of Life Sciences Zhejiang University Hangzhou Zhejiang 310058 China

The Fourth School of Clinical Medicine Zhejiang Chinese Medical University Hangzhou Zhejiang 310053 China

Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Affiliated Hangzhou First People's Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310006 China

Zhejiang University‐University of Edinburgh Institute (ZJU‐UoE Institute) University School of Medicine International Campus Zhejiang University Haining Zhejiang 314400 China

The Children's Hospital National Clinical Research Center for Child Health Zhejiang University School of Medicine Hangzhou Zhejiang 310003 China

Department of Cell Biology Zhejiang University School of Medicine Hangzhou Zhejiang 310058 China

Department of Biochemistry Department of Cardiology of Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 313000 China

International School of Medicine International Institutes of Medicine The 4th Affiliated Hospital of Zhejiang University School of Medicine Yiwu Zhejiang 322000 China

Department of Cell Biology Department of General Surgery of Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310016 China

Department of Central Laboratory The First People's Hospital of Huzhou Huzhou Zhejiang 313000 China

Cancer Center Zhejiang University Hangzhou Zhejiang 310058 China

Hangzhou Cancer Institution Affiliated Hangzhou Cancer Hospital Zhejiang University School of Medicine Zhejiang University Hangzhou Zhejiang 310002 China

College of Medicine and Veterinary Medicine The University of Edinburgh Edinburgh EH16 4SB UK

Key Laboratory for Cell and Gene Engineering of Zhejiang Province Hangzhou Zhejiang 310058 China

Future Health Laboratory Innovation Center of Yangtze River Delta Zhejiang University Jiaxing Zhejiang 314100 China

Funding

National Natural Science Foundation of China · National Key Research and Development Program of China · Fundamental Research Funds for the Central Universities

References (66)

Show source-provided references
1. 10.1016/S0140-6736(18)32822-810.1016/S0140-6736(18)32822-8 ↗
2. 10.1016/j.cmet.2019.09.01610.1016/j.cmet.2019.09.016 ↗
3. 10.1038/s41598-019-55291-810.1038/s41598-019-55291-8 ↗
4. 10.1146/annurev-pathol-121808-10213210.1146/annurev-pathol-121808-102132 ↗
5. 10.1038/nm.411410.1038/nm.4114 ↗
6. 10.1016/j.immuni.2019.09.02010.1016/j.immuni.2019.09.020 ↗
7. 10.1038/nri292110.1038/nri2921 ↗
8. 10.1172/JCI20031945110.1172/JCI200319451 ↗
9. 10.1172/JCI11793610.1172/JCI117936 ↗
10. 10.1038/nm0106-4110.1038/nm0106-41 ↗
11. 10.1016/j.cell.2014.05.01210.1016/j.cell.2014.05.012 ↗
12. 10.1194/jlr.M500294-JLR20010.1194/jlr.M500294-JLR200 ↗
13. 10.1038/nrendo.2015.18910.1038/nrendo.2015.189 ↗
14. 10.1172/JCI2988110.1172/JCI29881 ↗
15. 10.1172/JCI20031924610.1172/JCI200319246 ↗
16. 10.1073/pnas.110025510810.1073/pnas.1100255108 ↗
17. 10.1007/s00125-013-3139-y10.1007/s00125-013-3139-y ↗
18. 10.1126/science.767818310.1126/science.7678183 ↗
19. 10.1038/nrneph.2015.17510.1038/nrneph.2015.175 ↗
20. 10.1038/s41590-020-0750-110.1038/s41590-020-0750-1 ↗
21. 10.1016/j.cmet.2014.03.02910.1016/j.cmet.2014.03.029 ↗
22. 10.1074/jbc.M01169520010.1074/jbc.M011695200 ↗
23. 10.1161/01.ATV.0000251608.09329.9a10.1161/01.ATV.0000251608.09329.9a ↗
24. 10.1097/MOL.0b013e32832fa5c410.1097/MOL.0b013e32832fa5c4 ↗
25. 10.1016/j.jacc.2006.03.05210.1016/j.jacc.2006.03.052 ↗
26. 10.1016/j.cgh.2020.05.02610.1016/j.cgh.2020.05.026 ↗
27. Nguyen M. · J. Biol. Chem. · 2007 · 27 · 84
28. 10.1080/19490976.2018.151376510.1080/19490976.2018.1513765 ↗
29. 10.1136/gutjnl-2020-32226010.1136/gutjnl-2020-322260 ↗
30. 10.1053/j.gastro.2016.02.06610.1053/j.gastro.2016.02.066 ↗
31. 10.1016/j.phrs.2021.10588510.1016/j.phrs.2021.105885 ↗
32. 10.1038/s41574-022-00675-610.1038/s41574-022-00675-6 ↗
33. 10.1038/nm116610.1038/nm1166 ↗
34. 10.1210/endrev/bnz00910.1210/endrev/bnz009 ↗
35. 10.1038/s42255-021-00501-910.1038/s42255-021-00501-9 ↗
36. 10.1186/s11658-018-0108-y10.1186/s11658-018-0108-y ↗
37. 10.1128/MCB.00429-1510.1128/MCB.00429-15 ↗
38. 10.1126/science.125145610.1126/science.1251456 ↗
39. 10.1038/ijo.2016.18910.1038/ijo.2016.189 ↗
40. 10.1016/j.intimp.2021.10834710.1016/j.intimp.2021.108347 ↗
41. Wang J. · Diabetes · 2018 · 67
42. 10.1016/j.cmet.2016.11.01610.1016/j.cmet.2016.11.016 ↗
43. 10.1016/j.joca.2018.12.01510.1016/j.joca.2018.12.015 ↗
44. 10.1172/jci.insight.14675710.1172/jci.insight.146757 ↗
45. 10.1371/journal.pone.008615610.1371/journal.pone.0086156 ↗
46. 10.3322/caac.2149910.3322/caac.21499 ↗
47. Organization W. H. · J. Physiotherapy · 2014 · 60 · 114
48. 10.1038/ncb329510.1038/ncb3295 ↗
49. 10.1038/s41590-019-0400-710.1038/s41590-019-0400-7 ↗
50. 10.1016/0092-8674(88)90184-510.1016/0092-8674(88)90184-5 ↗
51. 10.1016/0092-8674(84)90257-510.1016/0092-8674(84)90257-5 ↗
52. 10.1161/CIRCULATIONAHA.111.08721310.1161/CIRCULATIONAHA.111.087213 ↗
53. 10.1016/j.cmet.2018.11.00210.1016/j.cmet.2018.11.002 ↗
54. 10.1038/nrm.2016.9610.1038/nrm.2016.96 ↗
55. 10.1002/j.1550-8528.1997.tb00591.x10.1002/j.1550-8528.1997.tb00591.x ↗
56. 10.1200/JCO.2016.67.428310.1200/JCO.2016.67.4283 ↗
57. 10.1016/j.cmet.2017.12.00210.1016/j.cmet.2017.12.002 ↗
58. 10.1016/S0092-8674(00)81410-510.1016/S0092-8674(00)81410-5 ↗
59. 10.1038/nature1198610.1038/nature11986 ↗
60. 10.1038/ncb347310.1038/ncb3473 ↗
61. 10.1038/s42255-018-0021-810.1038/s42255-018-0021-8 ↗
62. 10.1007/s10911-013-9310-810.1007/s10911-013-9310-8 ↗
63. 10.1016/j.cub.2017.09.01910.1016/j.cub.2017.09.019 ↗
64. 10.1038/ijo.2013.8210.1038/ijo.2013.82 ↗
65. 10.21769/BioProtoc.426510.21769/BioProtoc.4265 ↗
66. 10.1016/j.cmet.2014.02.00710.1016/j.cmet.2014.02.007 ↗