2,513
Views
40
CrossRef citations to date
0
Altmetric
Research Paper

GR-mediated FTO transactivation induces lipid accumulation in hepatocytes via demethylation of m6A on lipogenic mRNAs

, , , , ORCID Icon, , & show all
Pages 930-942 | Received 23 Sep 2019, Accepted 18 Feb 2020, Published online: 09 Mar 2020

References

  • Targher G, Bertolini L, Rodella S, et al. Associations between liver histology and cortisol secretion in subjects with nonalcoholic fatty liver disease. Clin Endocrinol (Oxf). 2006;64:337–341.
  • Candia R, Riquelme A, Baudrand R, et al. Overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue and portal hypercortisolism in non-alcoholic fatty liver disease. Liver Int. 2012;32:392–399.
  • Petta I, Dejager L, Ballegeer M, et al. The interactome of the glucocorticoid receptor and its influence on the actions of glucocorticoids in combatting inflammatory and infectious diseases. Microbiol Mol Biol Rev. 2016;80:495–522.
  • Hayashi R, Wada H, Ito K, et al. Effects of glucocorticoids on gene transcription. Eur J Pharmacol. 2004;500:51–62.
  • Rogatsky I, Wang JC, Derynck MK, et al. Target-specific utilization of transcriptional regulatory surfaces by the glucocorticoid receptor. Proc Natl Acad Sci U S A. 2003;100:13845–13850.
  • Wang JC, Gray NE, Kuo T, et al. Regulation of triglyceride metabolism by glucocorticoid receptor. Cell Biosci. 2012;2:19.
  • Marino JS, Stechschulte LA, Stec DE, et al. Glucocorticoid receptor beta induces hepatic steatosis by augmenting inflammation and inhibition of the peroxisome proliferator-activated receptor (PPAR) alpha. J Biol Chem. 2016;291:25776–25788.
  • Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316:889–894.
  • Scuteri A, Sanna S, Chen WM, et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 2007;3:e115.
  • Loos RJ, Bouchard C. FTO: the first gene contributing to common forms of human obesity. Obes Rev. 2008;9:246–250.
  • Liu SJ, Tang HL, He Q, et al. FTO is a transcriptional repressor to auto-regulate its own gene and potentially associated with homeostasis of body weight. J Mol Cell Biol. 2019;11:118–132.
  • Guo J, Ren W, Li A, et al. Fat mass and obesity-associated gene enhances oxidative stress and lipogenesis in nonalcoholic fatty liver disease. Dig Dis Sci. 2013;58:1004–1009.
  • Zhang J, Li S, Li J, et al. Expression and significance of fat mass and obesity associated gene and forkhead transcription factor O1 in non-alcoholic fatty liver disease. Chin Med J (Engl). 2014;127:3771–3776.
  • Chen J, Zhou X, Wu W, et al. FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice. J Physiol Biochem. 2015;71:405–413.
  • Zhang Y, Guo F, Zhao R. Hepatic expression of FTO and fatty acid metabolic genes changes in response to lipopolysaccharide with alterations in m(6)A modification of relevant mRNAs in the chicken. Br Poult Sci. 2016;57:628–635.
  • Lim A, Zhou J, Sinha RA, et al. Hepatic FTO expression is increased in NASH and its silencing attenuates palmitic acid-induced lipotoxicity. Biochem Biophys Res Commun. 2016;479:476–481.
  • Ikels K, Kuschel S, Fischer J, et al. FTO is a relevant factor for the development of the metabolic syndrome in mice. PloS One. 2014;9:e105349.
  • Jia G, Fu Y, Zhao X, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol. 2011;7:885–887.
  • Li Y, Wu K, Quan W, et al. The dynamics of FTO binding and demethylation from the m(6)A motifs. RNA Biol. 2019;16:1179–1189.
  • Meyer KD. m(6)A-mediated translation regulation. Biochim Biophys Acta Gene Regul Mech. 2019;1862:301–309.
  • Roundtree IA, Luo GZ, Zhang Z, et al. YTHDC1 mediates nuclear export of N(6)-methyladenosine methylated mRNAs. Elife. 2017;6:e31311.
  • Zhao X, Yang Y, Sun BF, et al. FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res. 2014;24:1403–1419.
  • Alarcon CR, Lee H, Goodarzi H, et al. N6-methyladenosine marks primary microRNAs for processing. Nature. 2015;519:482–485.
  • Zhang S, Zhao BS, Zhou A, et al. m(6)A demethylase ALKBH5 maintains tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program. Cancer Cell. 2017;31:591–606.e596.
  • Zhou J, Wan J, Gao X, et al. Dynamic m(6)A mRNA methylation directs translational control of heat shock response. Nature. 2015;526:591–594.
  • Wang X, Lu Z, Gomez A, et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature. 2014;505:117–120.
  • Xiao W, Adhikari S, Dahal U, et al. Nuclear m(6)A reader YTHDC1 regulates mRNA splicing. Mol Cell. 2016;61:507–519.
  • Zhang Y, Wang X, Zhang X, et al. RNA-binding protein YTHDF3 suppresses interferon-dependent antiviral responses by promoting FOXO3 translation. Proc Natl Acad Sci U S A. 2019;116:976–981.
  • Kang H, Zhang Z, Yu L, et al. FTO reduces mitochondria and promotes hepatic fat accumulation through RNA demethylation. J Cell Biochem. 2018;119:5676–5685.
  • Wu W, Feng J, Jiang D, et al. AMPK regulates lipid accumulation in skeletal muscle cells through FTO-dependent demethylation of N6-methyladenosine. Sci Rep. 2017;7:41606.
  • Leveille GA, Romsos DR, Yeh Y, et al. Lipid biosynthesis in the chick. A consideration of site of synthesis, influence of diet and possible regulatory mechanisms. Poult Sci. 1975;54:1075–1093.
  • Yeh YY, Leveille GA. Hepatic fatty acid synthesis and plasma free fatty acid levels in chicks subjected to short periods of food restriction and refeeding. J Nutr. 1970;100:1389–1397.
  • Cai Y, Song Z, Zhang X, et al. Increased de novo lipogenesis in liver contributes to the augmented fat deposition in dexamethasone exposed broiler chickens (Gallus gallus domesticus). Comp Biochem Physiol C Toxicol Pharmacol. 2009;150:164–169.
  • Kafri I, Rosebrough RW, McMurtry JP, et al. Corticosterone implants and supplemental dietary ascorbic acid effects on lipid metabolism in broiler chicks. Poult Sci. 1988;67:1356–1359.
  • Zhao N, Yang S, Jia Y, et al. Maternal betaine supplementation attenuates glucocorticoid-induced hepatic lipid accumulation through epigenetic modification in adult offspring rats. J Nutr Biochem. 2017;54:105–112.
  • Hu Y, Sun Q, Liu J, et al. In ovo injection of betaine alleviates corticosterone-induced fatty liver in chickens through epigenetic modifications. Sci Rep. 2017;7:40251.
  • Berlanga A, Guiu-Jurado E, Porras JA, et al. Molecular pathways in non-alcoholic fatty liver disease. Clin Exp Gastroenterol. 2014;7:221–239.
  • Schmid W, Strahle U, Schutz G, et al. Glucocorticoid receptor binds cooperatively to adjacent recognition sites. Embo J. 1989;8:2257–2263.
  • Kim M, Lee HA, Cho HM, et al. Histone deacetylase inhibition attenuates hepatic steatosis in rats with experimental Cushing’s syndrome. Korean J Physiol Pharmacol. 2018;22:23–33.
  • Kong X, Yu J, Bi J, et al. Glucocorticoids transcriptionally regulate miR-27b expression promoting body fat accumulation via suppressing the browning of white adipose tissue. Diabetes. 2015;64:393–404.
  • Zhang C, Samanta D, Lu H, et al. Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m(6)A-demethylation of NANOG mRNA. Proc Natl Acad Sci U S A. 2016;113:E2047–E2056.
  • Du H, Zhao Y, He J, et al. YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nat Commun. 2016;7:12626.
  • Luo JW, Zhou ZL, Zhang H, et al. Bone response of broiler chickens (Gallus gallus domesticus) induced by corticosterone. Comp Biochem Physiol A Mol Integr Physiol. 2013;164:410–416.
  • Su G, Letcher RJ, Farmahin R, et al. Photolysis of highly brominated flame retardants leads to time-dependent dioxin-responsive mRNA expression in chicken embryonic hepatocytes. Chemosphere. 2017;194:352–359.
  • Hu Y, Sun Q, Hu Y, et al. Corticosterone-Induced Lipogenesis Activation and Lipophagy Inhibition in Chicken Liver Are Alleviated by Maternal Betaine Supplementation. J Nutr. 2018;148:316–325.
  • Dominissini D, Moshitch-Moshkovitz S, Salmon-Divon M, et al. Transcriptome-wide mapping of N(6)-methyladenosine by m(6)A-seq based on immunocapturing and massively parallel sequencing. Nat Protoc. 2013;8:176–189.
  • Shen L, Liang Z, Gu X, et al. N(6)-methyladenosine RNA modification regulates shoot stem cell fate in arabidopsis. Dev Cell. 2016;38:186–200.
  • Du WW, Liu F, Shan SW, et al. Inhibition of dexamethasone-induced fatty liver development by reducing miR-17-5p levels. Mol Ther. 2015;23:1222–1233.
  • Luo GZ, MacQueen A, Zheng G, et al. Unique features of the m6A methylome in Arabidopsis thaliana. Nat Commun. 2014;5:5630.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.