Shift Work Promotes Adipogenesis Via Cortisol-dependent Downregulation of EGR3-HDAC6 Pathway

Overview

Journal Cell Death Discov

Date 2024 Mar 12

PMID 38467615

Authors

Xinxing Wan

Linghao Wang

Md Asaduzzaman Khan

Lin Peng

Keke Zhang

Xiaoying Sun

Xuan Yi

Zhouqi Wang

Ke Chen

Affiliations

Soon will be listed here.

Abstract

The disruption of circadian rhythms caused by long-term shift work can cause metabolic diseases such as obesity. Early growth response 3 (EGR3) is a member of early growth response (EGR) family, which is involved in several cellular responses, had been reported as a circadian rhythm gene in suprachiasmatic nucleus. In this research, EGR3 was found to be widely expressed in the different tissue of human and mice, and downregulated in adipose tissue of obese subjects and high-fat diet mice. Moreover, EGR3 was found negatively regulated by cortisol. In addition, EGR3 is a key negative modulator of hADSCs and 3T3-L1 adipogenesis via regulating HDAC6, which is a downstream target gene of EGR3 and a negative regulator of adipogenesis and lipogenesis. These findings may explain how circadian rhythm disorder induced by shift works can cause obesity. Our study revealed a potential therapeutic target to alleviate metabolic disorders in shift workers and may provide better health guidance to shift workers.

References

Russell T, Watad A, Bridgewood C, Rowe H, Khan A, Rao A . IL-17A and TNF Modulate Normal Human Spinal Entheseal Bone and Soft Tissue Mesenchymal Stem Cell Osteogenesis, Adipogenesis, and Stromal Function. Cells. 2021; 10(2). PMC: 7915379. DOI: 10.3390/cells10020341. View

Laermans J, Broers C, Beckers K, Vancleef L, Steensels S, Thijs T . Shifting the circadian rhythm of feeding in mice induces gastrointestinal, metabolic and immune alterations which are influenced by ghrelin and the core clock gene Bmal1. PLoS One. 2014; 9(10):e110176. PMC: 4199674. DOI: 10.1371/journal.pone.0110176. View

Nguyen N, de Oliveira Andrade F, Jin L, Zhang X, Macon M, Cruz M . Maternal intake of high n-6 polyunsaturated fatty acid diet during pregnancy causes transgenerational increase in mammary cancer risk in mice. Breast Cancer Res. 2017; 19(1):77. PMC: 5494892. DOI: 10.1186/s13058-017-0866-x. View

Zhou T, Jia D, Han J, Xu C, You X, Ge X . HDAC6 inhibition alleviates acute pulmonary embolism: a possible future therapeutic option. Folia Histochem Cytobiol. 2023; 61(1):56-67. DOI: 10.5603/FHC.a2023.0006. View

Chen W, Jiang Y, Han J, Hu J, He T, Yan T . Atgl deficiency induces podocyte apoptosis and leads to glomerular filtration barrier damage. FEBS J. 2017; 284(7):1070-1081. DOI: 10.1111/febs.14038. View

Mookerjee-Basu J, Hooper R, Gross S, Schultz B, Go C, Samakai E . Suppression of Ca signals by EGR4 controls Th1 differentiation and anti-cancer immunity in vivo. EMBO Rep. 2020; 21(5):e48904. PMC: 7202224. DOI: 10.15252/embr.201948904. View

Aggarwal A, Costa M, Rivero-Gutierrez B, Ji L, Morgan S, Feldman B . The Circadian Clock Regulates Adipogenesis by a Per3 Crosstalk Pathway to Klf15. Cell Rep. 2017; 21(9):2367-2375. PMC: 5728416. DOI: 10.1016/j.celrep.2017.11.004. View

Porterfield V, Mintz E . Temporal patterns of light-induced immediate-early gene expression in the suprachiasmatic nucleus. Neurosci Lett. 2009; 463(1):70-3. DOI: 10.1016/j.neulet.2009.07.066. View

Chen Z, Torrens J, Anand A, Spiegelman B, Friedman J . Krox20 stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms. Cell Metab. 2005; 1(2):93-106. DOI: 10.1016/j.cmet.2004.12.009. View

10.

Lundh M, Petersen P, Isidor M, Kazoka-Sorensen D, Plucinska K, Shamsi F . Afadin is a scaffold protein repressing insulin action via HDAC6 in adipose tissue. EMBO Rep. 2019; 20(8):e48216. PMC: 6680131. DOI: 10.15252/embr.201948216. View

11.

Kaufmann K, Bach K, Thiel G . The extracellular signal-regulated protein kinases Erk1/Erk2 stimulate expression and biological activity of the transcriptional regulator Egr-1. Biol Chem. 2001; 382(7):1077-81. DOI: 10.1515/BC.2001.135. View

12.

Kwon Y, Kim M, Kim Y, Jeong M, Jung H, Jeoung D . EGR3-HDAC6-IL-27 Axis Mediates Allergic Inflammation and Is Necessary for Tumorigenic Potential of Cancer Cells Enhanced by Allergic Inflammation-Promoted Cellular Interactions. Front Immunol. 2021; 12:680441. PMC: 8257050. DOI: 10.3389/fimmu.2021.680441. View

13.

Iwayama H, Hirase S, Nomura Y, Ito T, Morita H, Otake K . Spontaneous adrenocorticotropic hormone (ACTH) normalisation due to tumour regression induced by metyrapone in a patient with ectopic ACTH syndrome: case report and literature review. BMC Endocr Disord. 2018; 18(1):19. PMC: 5872391. DOI: 10.1186/s12902-018-0246-2. View

14.

Hou T, Su W, Guo Z, Gong M . A Novel Diabetic Mouse Model for Real-Time Monitoring of Clock Gene Oscillation and Blood Pressure Circadian Rhythm. J Biol Rhythms. 2018; 34(1):51-68. PMC: 6757342. DOI: 10.1177/0748730418803719. View

15.

Martocchia A, Curto M, Toussan L, Stefanelli M, Falaschi P . Pharmacological strategies against glucocorticoid-mediated brain damage during chronic disorders. Recent Pat CNS Drug Discov. 2011; 6(3):196-204. DOI: 10.2174/157488911796958020. View

16.

Cheng M, He H, Wang D, Xu L, Wang B, Ho K . Shift work and ischaemic heart disease: meta-analysis and dose-response relationship. Occup Med (Lond). 2019; 69(3):182-188. DOI: 10.1093/occmed/kqz020. View

17.

Gast H, Muller A, Lopez M, Meier D, Huber R, Dechent F . CD40 activation induces NREM sleep and modulates genes associated with sleep homeostasis. Brain Behav Immun. 2012; 27(1):133-44. DOI: 10.1016/j.bbi.2012.10.004. View

18.

He K, Zhang J, Liu J, Cui Y, Liu L, Ye S . Functional genomics study of protein inhibitor of activated STAT1 in mouse hippocampal neuronal cells revealed by RNA sequencing. Aging (Albany NY). 2021; 13(6):9011-9027. PMC: 8034905. DOI: 10.18632/aging.202749. View

19.

Liu C, Tang X, Gong Z, Zeng W, Hou Q, Lu R . Circadian Rhythm Sleep Disorders: Genetics, Mechanisms, and Adverse Effects on Health. Front Genet. 2022; 13:875342. PMC: 9099045. DOI: 10.3389/fgene.2022.875342. View

20.

Wan X, Zhu L, Zhao L, Peng L, Xiong J, Yang W . hPER3 promotes adipogenesis via hHSP90AA1-mediated inhibition of Notch1 pathway. Cell Death Dis. 2021; 12(4):301. PMC: 7979882. DOI: 10.1038/s41419-021-03584-0. View