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

Marcella E. O'Reilly; Sebastian Ho; Johana Coronel; Lucie Zhu; Wen Liu; Chenyi Xue; Eunyoung Kim; Esther Cynn; Caio V. Matias; Rajesh Kumar Soni; Chen Wang; Iuliana Ionita-Laza; Robert C. Bauer; Leila Ross; Yiying Zhang; Silvia Corvera; Susan K. Fried; Muredach P. Reilly

doi:10.1016/j.celrep.2024.114240

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

Marcella E. O'Reilly, Sebastian Ho, Johana Coronel, Lucie Zhu, Wen Liu, Chenyi Xue, Eunyoung Kim, Esther Cynn, Caio V. Matias, Rajesh Kumar Soni, Chen Wang, Iuliana Ionita-Laza, Robert C. Bauer, Leila Ross, Yiying Zhang, Silvia Corvera, Susan K. Fried, Muredach P. Reilly

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	114240
Journal	Cell Reports
Volume	43
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2024.114240
State	Published - 28 May 2024

Keywords

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

Access to Document

10.1016/j.celrep.2024.114240

Cite this

O'Reilly, M. E., Ho, S., Coronel, J., Zhu, L., Liu, W., Xue, C., Kim, E., Cynn, E., Matias, C. V., Soni, R. K., Wang, C., Ionita-Laza, I., Bauer, R. C., Ross, L., Zhang, Y., Corvera, S., Fried, S. K., & Reilly, M. P. (2024). linc-ADAIN, a human adipose lincRNA, regulates adipogenesis by modulating KLF5 and IL-8 mRNA stability. Cell Reports, 43(5), Article 114240. https://doi.org/10.1016/j.celrep.2024.114240

@article{3ee505fb330448b1a26271fbfca629f0,

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

abstract = "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.",

keywords = "CP: Metabolism, CP: Molecular biology, HuR, IGF2BP2, IL-8, KLF5, adipogenesis, linc-ADAIN, linc-DMRT2, linc01230, long non-coding RNA, obesity",

author = "O'Reilly, {Marcella E.} and Sebastian Ho and Johana Coronel and Lucie Zhu and Wen Liu and Chenyi Xue and Eunyoung Kim and Esther Cynn and Matias, {Caio V.} and Soni, {Rajesh Kumar} and Chen Wang and Iuliana Ionita-Laza and Bauer, {Robert C.} and Leila Ross and Yiying Zhang and Silvia Corvera and Fried, {Susan K.} and Reilly, {Muredach P.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = may,

day = "28",

doi = "10.1016/j.celrep.2024.114240",

language = "English",

volume = "43",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "5",

}

O'Reilly, ME, Ho, S, Coronel, J, Zhu, L, Liu, W, Xue, C, Kim, E, Cynn, E, Matias, CV, Soni, RK, Wang, C, Ionita-Laza, I, Bauer, RC, Ross, L, Zhang, Y, Corvera, S, Fried, SK & Reilly, MP 2024, 'linc-ADAIN, a human adipose lincRNA, regulates adipogenesis by modulating KLF5 and IL-8 mRNA stability', Cell Reports, vol. 43, no. 5, 114240. https://doi.org/10.1016/j.celrep.2024.114240

TY - JOUR

T1 - linc-ADAIN, a human adipose lincRNA, regulates adipogenesis by modulating KLF5 and IL-8 mRNA stability

AU - O'Reilly, Marcella E.

AU - Ho, Sebastian

AU - Coronel, Johana

AU - Zhu, Lucie

AU - Liu, Wen

AU - Xue, Chenyi

AU - Kim, Eunyoung

AU - Cynn, Esther

AU - Matias, Caio V.

AU - Soni, Rajesh Kumar

AU - Wang, Chen

AU - Ionita-Laza, Iuliana

AU - Bauer, Robert C.

AU - Ross, Leila

AU - Zhang, Yiying

AU - Corvera, Silvia

AU - Fried, Susan K.

AU - Reilly, Muredach P.

PY - 2024/5/28

Y1 - 2024/5/28

N2 - 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.

AB - 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.

KW - CP: Metabolism

KW - CP: Molecular biology

KW - HuR

KW - IGF2BP2

KW - IL-8

KW - KLF5

KW - adipogenesis

KW - linc-ADAIN

KW - linc-DMRT2

KW - linc01230

KW - long non-coding RNA

KW - obesity

UR - http://www.scopus.com/inward/record.url?scp=85192730142&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2024.114240

DO - 10.1016/j.celrep.2024.114240

M3 - Article

AN - SCOPUS:85192730142

SN - 2211-1247

VL - 43

JO - Cell Reports

JF - Cell Reports

IS - 5

M1 - 114240

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this