linc-ADAIN, a human adipose lincRNA, regulates adipogenesis by modulating KLF5 and IL-8 mRNA stability.

Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE

Original Publication: [Cambridge, MA] : Cell Press, c 2012-

RNA, Long Noncoding*/genetics ; RNA, Long Noncoding*/metabolism ; Kruppel-Like Transcription Factors*/metabolism ; Kruppel-Like Transcription Factors*/genetics ; Adipogenesis*/genetics ; RNA Stability*/genetics ; Interleukin-8*/metabolism ; Interleukin-8*/genetics; Humans ; Animals ; Mice ; RNA-Binding Proteins/metabolism ; RNA-Binding Proteins/genetics ; Adipocytes/metabolism ; Adipose Tissue/metabolism ; Obesity/metabolism ; Obesity/genetics ; Obesity/pathology ; RNA, Messenger/metabolism ; RNA, Messenger/genetics ; Male ; Inflammation/pathology ; Inflammation/genetics ; Inflammation/metabolism

Adipose tissue remodeling and dysfunction, characterized by elevated inflammation and insulin resistance, play a central role in obesity-related development of type 2 diabetes (T2D) and cardiovascular diseases. Long intergenic non-coding RNAs (lincRNAs) are important regulators of cellular functions. Here, we describe the functions of linc-ADAIN (adipose anti-inflammatory), an adipose lincRNA that is downregulated in white adipose tissue of obese humans. We demonstrate that linc-ADAIN knockdown (KD) increases KLF5 and interleukin-8 (IL-8) mRNA stability and translation by interacting with IGF2BP2. Upregulation of KLF5 and IL-8, via linc-ADAIN KD, leads to an enhanced adipogenic program and adipose tissue inflammation, mirroring the obese state, in vitro and in vivo. KD of linc-ADAIN in human adipose stromal cell (ASC) hTERT adipocytes implanted into mice increases adipocyte size and macrophage infiltration compared to implanted control adipocytes, mimicking hallmark features of obesity-induced adipose tissue remodeling. linc-ADAIN is an anti-inflammatory lincRNA that limits adipose tissue expansion and lipid storage.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nat Methods. 2012 Jun 28;9(7):676-82. (PMID: 22743772)
EMBO Rep. 2018 Dec;19(12):. (PMID: 30467236)
PLoS Genet. 2014 Aug 07;10(8):e1004517. (PMID: 25102180)
RNA. 2009 Jan;15(1):104-15. (PMID: 19029303)
EMBO J. 1998 Jun 15;17(12):3448-60. (PMID: 9628880)
Cell Metab. 2015 Apr 7;21(4):609-21. (PMID: 25863250)
Nat Rev Mol Cell Biol. 2023 Jun;24(6):430-447. (PMID: 36596869)
Nature. 2006 Dec 14;444(7121):860-7. (PMID: 17167474)
PLoS Genet. 2013 Jun;9(6):e1003569. (PMID: 23818866)
Nature. 2015 Feb 12;518(7538):187-196. (PMID: 25673412)
Genes Dev. 2011 Sep 15;25(18):1915-27. (PMID: 21890647)
Nat Metab. 2020 May;2(5):397-412. (PMID: 32440655)
Nucleic Acids Res. 2022 Jul 5;50(W1):W216-W221. (PMID: 35325185)
Cell. 2013 Jul 3;154(1):26-46. (PMID: 23827673)
Oncotarget. 2015 Dec 22;6(41):43791-805. (PMID: 26544730)
Clin Exp Immunol. 2018 Jun;192(3):325-336. (PMID: 29393507)
Arterioscler Thromb Vasc Biol. 2014 Apr;34(4):902-12. (PMID: 24504737)
Cell Metab. 2015 May 5;21(5):764-776. (PMID: 25921091)
Obesity (Silver Spring). 2014 Aug;22(8):1781-5. (PMID: 24862299)
Science. 2015 Feb 27;347(6225):1010-4. (PMID: 25678556)
iScience. 2021 Dec 25;25(1):103680. (PMID: 35036870)
J Clin Invest. 1997 May 15;99(10):2416-22. (PMID: 9153284)
Adipocyte. 2015 Jan 20;4(4):248-55. (PMID: 26451280)
J Am Coll Cardiol. 2010 Sep 28;56(14):1113-32. (PMID: 20863953)
J Biol Chem. 2019 Aug 2;294(31):11944-11951. (PMID: 31209109)
BMC Bioinformatics. 2015 May 22;16:169. (PMID: 25994840)
Cell Metab. 2014 Dec 2;20(6):1049-58. (PMID: 25456741)
Nat Rev Genet. 2018 Sep;19(9):535-548. (PMID: 29795125)
J Proteome Res. 2016 Feb 5;15(2):628-37. (PMID: 26767403)
Acta Physiol (Oxf). 2020 Jan;228(1):e13298. (PMID: 31077538)
Nat Biotechnol. 2016 May;34(5):525-7. (PMID: 27043002)
Endocr Rev. 2022 Jan 12;43(1):35-60. (PMID: 34100954)
BMC Genomics. 2011 Mar 16;12:152. (PMID: 21410980)
J Clin Lab Anal. 2022 Jun;36(6):e24442. (PMID: 35441392)
Nat Rev Cardiol. 2023 Jul;20(7):475-494. (PMID: 36927772)
Stem Cells Int. 2018 Mar 15;2018:4217259. (PMID: 29736175)
Front Mol Neurosci. 2018 Jan 09;10:437. (PMID: 29375300)
Cell Res. 2018 May;28(5):507-517. (PMID: 29686311)
Int J Mol Sci. 2019 May 13;20(9):. (PMID: 31085992)
Am J Physiol Endocrinol Metab. 2004 Jan;286(1):E8-13. (PMID: 13129857)
Nat Commun. 2019 May 30;10(1):2375. (PMID: 31147543)
Ann Transl Med. 2023 Mar 15;11(5):198. (PMID: 37007546)
Nat Rev Cancer. 2021 Jul;21(7):446-460. (PMID: 33953369)
J Clin Invest. 2003 Dec;112(12):1821-30. (PMID: 14679177)
Cold Spring Harb Perspect Biol. 2018 Jun 1;10(6):. (PMID: 28716885)
Genome Res. 2012 Sep;22(9):1775-89. (PMID: 22955988)
Nat Biotechnol. 2008 Dec;26(12):1367-72. (PMID: 19029910)
Cell Death Discov. 2022 May 14;8(1):261. (PMID: 35568705)
J Dent Res. 2008 Aug;87(8):772-6. (PMID: 18650551)
J Proteome Res. 2011 Apr 1;10(4):1794-805. (PMID: 21254760)
Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):369-376. (PMID: 30454889)
Mol Metab. 2022 Jun;60:101473. (PMID: 35292404)
Nucleic Acids Res. 2023 Jan 6;51(D1):D638-D646. (PMID: 36370105)
Endocrinology. 2007 Feb;148(2):868-77. (PMID: 17082259)
Cell Cycle. 2007 Jun 1;6(11):1288-92. (PMID: 17534146)
Nucleic Acids Res. 2017 Jul 3;45(W1):W550-W553. (PMID: 28431173)
J Immunol. 2011 Feb 15;186(4):2482-94. (PMID: 21220697)
Nucleic Acids Res. 2020 Jan 8;48(D1):D101-D110. (PMID: 31732741)
RNA Biol. 2014;11(2):124-33. (PMID: 24525793)
Sci Transl Med. 2018 Jun 20;10(446):. (PMID: 29925637)
Cell Rep. 2015 May 19;11(7):1110-22. (PMID: 25959816)
Cell Metab. 2019 Nov 5;30(5):963-975.e7. (PMID: 31668873)
Cell Mol Life Sci. 2013 Aug;70(15):2657-75. (PMID: 23069990)
Cell Death Differ. 2020 Jun;27(6):1782-1794. (PMID: 31804607)
J Transl Med. 2013 Mar 12;11:63. (PMID: 23497455)
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W361-7. (PMID: 24829458)
Front Biosci (Landmark Ed). 2012 Jan 01;17(1):189-205. (PMID: 22201738)
Cell Biosci. 2020 Jul 20;10:88. (PMID: 32699606)
BMC Cancer. 2022 Mar 29;22(1):343. (PMID: 35351056)
J Lipid Res. 2012 Dec;53(12):2791-6. (PMID: 22993232)
Nat Cell Biol. 2018 Mar;20(3):285-295. (PMID: 29476152)
Genome Res. 2019 Dec;29(12):2073-2087. (PMID: 31537640)
Nat Protoc. 2006;1(6):2856-60. (PMID: 17406544)
Nat Commun. 2020 Jan 10;11(1):213. (PMID: 31924774)
PLoS One. 2016 Jun 16;11(6):e0157364. (PMID: 27310578)
Cancer Commun (Lond). 2022 Feb;42(2):117-140. (PMID: 35019235)
Nat Med. 2012 Sep;18(9):1407-12. (PMID: 22863787)
Clin Cancer Res. 2008 Nov 1;14(21):6735-41. (PMID: 18980965)
Biochem Pharmacol. 2022 Dec;206:115305. (PMID: 36272599)
Tissue Eng Part A. 2019 Jun;25(11-12):842-854. (PMID: 30306830)
Nature. 2022 Mar;603(7903):926-933. (PMID: 35296864)
Cancer Sci. 2021 Jun;112(6):2097-2117. (PMID: 33811715)
Cells. 2022 Jul 31;11(15):. (PMID: 35954201)
FEBS Lett. 2008 Jun 18;582(14):1977-86. (PMID: 18342629)
Nat Med. 2016 Mar;22(3):312-8. (PMID: 26808348)
Cell Metab. 2005 Jan;1(1):27-39. (PMID: 16054042)
J Clin Invest. 2020 Dec 1;130(12):6688-6699. (PMID: 33164985)
Angiogenesis. 2022 Nov;25(4):439-453. (PMID: 35857195)
Mol Cell. 2005 Sep 16;19(6):777-89. (PMID: 16168373)

R01 HL150359 United States HL NHLBI NIH HHS; R01 DK089101 United States DK NIDDK NIH HHS; R01 HL132561 United States HL NHLBI NIH HHS; R01 HL113147 United States HL NHLBI NIH HHS; R01 DK123028 United States DK NIDDK NIH HHS; R01 HL166916 United States HL NHLBI NIH HHS; R01 DK137403 United States DK NIDDK NIH HHS

Keywords: CP: Metabolism; CP: Molecular biology; HuR; IGF2BP2; IL-8; KLF5; adipogenesis; linc-ADAIN; linc-DMRT2; linc01230; long non-coding RNA; obesity

0 (RNA, Long Noncoding)
0 (Kruppel-Like Transcription Factors)
0 (Interleukin-8)
0 (KLF5 protein, human)
0 (RNA-Binding Proteins)
0 (IGF2BP2 protein, human)
0 (RNA, Messenger)

Date Created: 20240516 Date Completed: 20240531 Latest Revision: 20240822

20240822

PMC11334222

10.1016/j.celrep.2024.114240

38753486