Hostname: page-component-848d4c4894-x24gv Total loading time: 0 Render date: 2024-06-05T01:01:35.729Z Has data issue: false hasContentIssue false
  • English
  • Français

Choline-mediated hepatic lipid homoeostasis in yellow catfish: unravelling choline’s lipotropic and methyl donor functions and significance of ire-1α signalling pathway

Published online by Cambridge University Press:  29 August 2023

Yu-Feng Song Open the ORCID record for Yu-Feng Song [Opens in a new window] ,
Zhen-Yu Bai ,
Zhi Luo Open the ORCID record for Zhi Luo [Opens in a new window] ,
Ling-Jiao Wang  and
Hua Zheng Open the ORCID record for Hua Zheng [Opens in a new window]
Yu-Feng Song*
Affiliation:
Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan 430070, People’s Republic of China
Zhen-Yu Bai
Affiliation:
Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan 430070, People’s Republic of China
Zhi Luo
Affiliation:
Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan 430070, People’s Republic of China Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, People’s Republic of China
Ling-Jiao Wang
Affiliation:
Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan 430070, People’s Republic of China
Hua Zheng
Affiliation:
Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan 430070, People’s Republic of China
*
*Corresponding author: Yu-Feng Song, email syf880310@mail.hzau.edu.cn
Get access Rights & Permissions [Opens in a new window]

Abstract

Choline plays a crucial role in hepatic lipid homeostasis by acting as a major methyl-group donor. However, despite this well-accepted fact, no study has yet explored how choline’s methyl-donor function contributes to preventing hepatic lipid dysregulation. Moreover, the potential regulatory role of Ire-1α, an ER-transmembrane transducer for the unfolded protein response (UPRer), in choline-mediated hepatic lipid homeostasis remains unexplored. Thus, this study investigated the mechanism by which choline prevents hepatic lipid dysregulation, focusing on its role as a methyl-donor and the involvement of Ire-1α in this process. To this end, a model animal for lipid metabolism, yellow catfish (Pelteobagrus fulvidraco) were fed two different diets (adequate or deficient choline diets) in vivo for 10 weeks. The key findings of studies are as follows: 1. Dietary choline, upregulated selected lipolytic and fatty acid β-oxidation transcripts promoting hepatic lipid homeostasis. 2. Dietary choline ameliorated UPRer and prevented hepatic lipid dysregulation mainly through ire-1α signalling, not perk or atf-6α signalling. 3. Choline inhibited the transcriptional expression level of ire-1α by activating site-specific DNA methylations in the promoter of ire-1α. 4. Choline-mediated ire-1α methylations reduced Ire-1α/Fas interactions, thereby further inhibiting Fas activity and reducing lipid droplet deposition. These results offer a novel insight into the direct and indirect regulation of choline on lipid metabolism genes and suggests a potential crosstalk between ire-1α signalling and choline-deficiency-induced hepatic lipid dysregulation, highlighting the critical contribution of choline as a methyl-donor in maintaining hepatic lipid homeostasis.

Keywords

CholineHepatic lipid dysregulationUnfolded protein responseIre-1αMethylation
Type
Research Article
Information
British Journal of Nutrition , Volume 131 , Issue 2 , 28 January 2024 , pp. 202 - 213
Check for updates
Copyright
© The Author(s), 2023. Published by Cambridge University Press on behalf of The Nutrition Society

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

†

First author

References

Ooi, GJ, Meikle, PJ, Huynh, K, et al. (2021) Hepatic lipidomic remodeling in severe obesity manifests with steatosis and does not evolve with non-alcoholic steatohepatitis. J Hepatol 75, 524–535.Google Scholar
Luo, Z, Wei, CC, Ye, HM, et al. (2016) Effect of dietary choline levels on growth performance, lipid deposition and metabolism in juvenile yellow catfish Pelteobagrus fulvidraco . Comp Biochem Physiol Part B Biochem Mol Biol 202, 1–7.Google Scholar
Tahan, V, Sonsuz, A, Imeryuz, N, et al. (2004) 604 Parenteral iron enhances liver injury in methionine choline deficient diet induced non-alcoholic steatohepatitis in rats. J Hepatol 40, 177–177.Google Scholar
Corbin, KD & Zeisel, SH (2012) Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression. Curr Opin Gastroenterol 28, 159–165.Google Scholar
Liu, A, Pirozzi, I, Codabaccus, BM, et al. (2021) Effects of dietary choline on liver lipid composition, liver histology and plasma biochemistry of juvenile yellowtail kingfish (Seriola lalandi). Br J Nutr 125, 1344–1358.Google Scholar
Mahmoud, AM & Ali, MM (2019) Methyl donor micronutrients that modify DNA methylation and cancer outcome. Nutrients 11, 608.Google Scholar
Park, LK, Friso, S & Choi, SW (2012) Nutritional influences on epigenetics and age-related disease. Proc Nutr Soc 71, 75–83.Google Scholar
Zeisel, S (2017) Choline, other methyl-donors and epigenetics. Nutrients 9, 445.Google Scholar
Yoon, A, Tammen, SA, Park, S, et al. (2017) Genome-wide hepatic DNA methylation changes in high-fat diet-induced obese mice. Nutr Res Pract 11, 105–113.Google Scholar
Mittelstraß, K & Waldenberger, M (2018) DNA methylation in human lipid metabolism and related diseases. Curr Opin Lipidol 29, 116–124.Google Scholar
Jones, AC, Irvin, MR, Claas, SA, et al. (2021) Lipid phenotypes and DNA methylation: a review of the literature. Curr Atheroscler Rep 23, 71.Google Scholar
Jacquemyn, J, Cascalho, A & Goodchild, RE (2017) The ins and outs of endoplasmic reticulum controlled lipid biosynthesis. EMBO Rep 18, 1905–1921.Google Scholar
Wilfling, F, Wang, H, Haas, JT, et al. (2013) Triacylglycerol synthesis enzymes mediate lipid droplet growth by relocalizing from the ER to lipid droplets. Dev Cell 24, 384–399.Google Scholar
Fu, S, Yang, L, Li, P, et al. (2011) Hotamisligil, aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature 473, 528–531.Google Scholar
Lebeaupin, C, Vallée, D, Hazari, Y, et al. (2018) Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease. J Hepatol 69, 927–947.Google Scholar
Han, H, Hu, J, Lau, MY, et al. (2013) Altered methylation and expression of ER-associated degradation factors in long-term alcohol and constitutive ER stress-induced murine hepatic tumors. Front Genet 31, 224.Google Scholar
Ramos-Lopez, O, Riezu-Boj, JI, Milagro, FI, et al. (2018) Project, DNA methylation signatures at endoplasmic reticulum stress genes are associated with adiposity and insulin resistance. Mol Genet Metab 123, 50–58.Google Scholar
Song, YF, Hogstrand, C, Wei, CC, et al. (2017) Endoplasmic reticulum (ER) stress and cAMP/PKA pathway mediated Zn-induced hepatic lipolysis. Environ Pollut 228, 256–264.Google Scholar
Nasiri-Ansari, N, Nikolopoulou, C, Papoutsi, K, et al. (2021) Empagliflozin attenuates Non-Alcoholic Fatty Liver Disease (NAFLD) in high fat diet fed ApoE (-/-) mice by activating autophagy and reducing ER stress and apoptosis. Int J Mol Sci 22, 818.Google Scholar
Gong, G, Dan, C, Xiao, S, et al. (2018) Chromosomal-level assembly of yellow catfish genome using third-generation DNA sequencing and Hi-C analysis. GigaScience 7, 120.Google Scholar
Sato, Y, Hashiguchi, Y & Nishida, M (2009) Temporal pattern of loss/persistence of duplicate genes involved in signal transduction and metabolic pathways after teleost-specific genome duplication. BMC Evol Biol 9, 127.Google Scholar
Wei, CC, Luo, Z, Hogstrand, C, et al. (2018) Zinc reduces hepatic lipid deposition and activates lipophagy via Zn2+/MTF-1/PPARα and Ca2+/CaMKKβ/AMPK pathways. FASEB J 32, 6666–6680.Google Scholar
Song, YF, Luo, Z, Zhang, LH, et al. (2016) Endoplasmic reticulum stress and disturbed calcium homeostasis are involved in copper-induced alteration in hepatic lipid metabolism in yellow catfish Pelteobagrus fulvidraco . Chemosphere 144, 2443–2453.Google Scholar
Song, YF, Hogstrand, C, Ling, SC, et al. (2020) Creb-Pgc1α pathway modulates the interaction between lipid droplets and mitochondria and influences high fat diet-induced changes of lipid metabolism in the liver and isolated hepatocytes of yellow catfish. J Nutr Biochem 80, 108364.Google Scholar
Zhao, T, Yang, SB, Chen, GH, et al. (2020) Dietary glucose increases glucose absorption and lipid deposition via SGLT1/2 signaling and acetylated ChREBP in the intestine and isolated intestinal epithelial cells of yellow catfish. J Nutr 150, 1790–1798.Google Scholar
Vandesompele, J, Preter, KD, Pattyn, F, et al. (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3, 0034.Google Scholar
Su, H, Yang, F, Wang, Q, et al. (2017) Vps34 acetylation controls its lipid kinase activity and the initiation of canonical and non-canonical autophagy. Mol Cell 67, 1e15.Google Scholar
Xu, YH, Xu, YC, Hogstrand, C, et al. (2020) Waterborne copper exposure up-regulated lipid deposition through the methylation of GRP78 and PGC1α of grass carp Ctenopharyngodon Idella . Ecotoxicol Environ Saf 205, 111089.Google Scholar
Song, YF, Xu, YH, Zhuo, MQ, et al. (2018) CREB element is essential for unfolded protein response (UPR) mediating the Cu-induced changes of hepatic lipogenic metabolism in Chinese yellow catfish (Pelteobagrus fulvidraco). Aquat Toxicol 203, 69–79.Google Scholar
Sun, WW, ShangGuan, T, Zhu, P, et al. (2020) Role of hepatic neuropeptide Y-Y1 receptors in a methionine-choline-deficient model of non-alcoholic steatohepatitis. Life Sci 245, 117356.Google Scholar
Yao, ZM, Jamil, H & Vance, DE (1990) Choline deficiency causes translocation of CTP: phosphocholine cytidylyltransferase from cytosol to endoplasmic reticulum in rat liver. J Biol Chem 265, 4326–4331.Google Scholar
Muraki, Y, Makita, Y, Yamasaki, M, et al. (2017) Elevation of liver endoplasmic reticulum stress in a modified choline-deficient l-amino acid-defined diet-fed non-alcoholic steatohepatitis mouse model. Biochem Biophys Res Commun 486, 632–638.Google Scholar
Minami, S, Miura, K, Ishioka, M, et al. (2019) Homocysteine supplementation ameliorates steatohepatitis induced by a choline-deficient diet in mice. Hepatol Res 49, 189–200.Google Scholar
Tan, X, Liu, R, Zhang, Y, et al. (2021) Integrated analysis of the methylome and transcriptome of chickens with fatty liver hemorrhagic syndrome. BMC Genomics 22, 8.Google Scholar
Matsuzaki, H, Miyajima, Y, Fukamizu, A, et al. (2021) Orientation of mouse H19 ICR affects imprinted H19 gene expression through promoter methylation-dependent and -independent mechanisms. Commun Biol 4, 1410.Google Scholar
Han, H, Hu, J, Lau, MY, et al. (2013) Altered methylation and expression of ER-associated degradation factors in long-term alcohol and constitutive ER stress-induced murine hepatic tumors. Front Genet 4, 224.Google Scholar
Cordero, P, Gomez-Uriz, AM & Campion, J (2013) Dietary supplementation with methyl donors reduces fatty liver and modifies the fatty acid synthase DNA methylation profile in rats fed an obesogenic diet. Genes Nutr 8, 105–113.Google Scholar
Sivanesan, S, Taylor, A, Zhang, J, et al. (2018) Betaine and choline improve lipid homeostasis in obesity by participation in mitochondrial oxidative demethylation. Front Nutr 5, 61.Google Scholar
Hansen, AKG, Kortner, TM, Denstadli, V, et al. (2020) Dose-response relationship between dietary choline and lipid accumulation in pyloric enterocytes of Atlantic salmon (Salmo salar L.) in seawater. Br J Nutr 123, 1081–1093.Google Scholar
Supplementary material: File

Song et al. supplementary material

Tables S1-S3 and Figures S1-S4

Download Song et al. supplementary material(File)
File 549.7 KB