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http://dx.doi.org/10.5713/ab.21.0341

Mechanistic target of rapamycin and an extracellular signaling-regulated kinases 1 and 2 signaling participate in the process of acetate regulating lipid metabolism and hormone-sensitive lipase expression  

Li, Yujuan (Department of Animal Science, Shandong Agricultural University)
Fu, Chunyan (Department of Animal Science, Shandong Agricultural University)
Liu, Lei (Department of Animal Science, Shandong Agricultural University)
Liu, Yongxu (Qingdao Kangda Food Co., LTD.)
Li, Fuchang (Department of Animal Science, Shandong Agricultural University)
Publication Information
Animal Bioscience / v.35, no.9, 2022 , pp. 1444-1453 More about this Journal
Abstract
Objective: Acetate plays an important role in host lipid metabolism. However, the network of acetate-regulated lipid metabolism remains unclear. Previous studies show that mitogen-activated protein kinases (MAPKs) and mechanistic target of rapamycin (mTOR) play a crucial role in lipid metabolism. We hypothesize that acetate could affect MAPKs and/or mTOR signaling and then regulate lipid metabolism. The present study investigated whether any cross talk occurs among MAPKs, mTOR and acetate in regulating lipid metabolism. Methods: The ceramide C6 (an extracellular signaling-regulated kinases 1 and 2 [ERK1/2] activator) and MHY1485 (a mTOR activator) were used to treat rabbit adipose-derived stem cells (ADSCs) with or without acetate, respectively. Results: It indicated that acetate (9 mM) treatment for 48 h decreased the lipid deposition in rabbit ADSCs. Acetate treatment decreased significantly phosphorylated protein levels of ERK1/2 and mTOR but significantly increased mRNA level of hormone-sensitive lipase (HSL). Acetate treatment did not significantly alter the phosphorylated protein level of p38 MAPK and c-Jun aminoterminal kinase (JNK). Activation of ERK1/2 and mTOR by respective addition in media with ceramide C6 and MHY1485 significantly attenuated decreased lipid deposition and increased HSL expression caused by acetate. Conclusion: Our results suggest that ERK1/2 and mTOR signaling pathways are associated with acetate regulated HSL gene expression and lipid deposition.
Keywords
Acetate; Extracellular Signaling-regulated Kinases 1 and 2 (ERK1/2); Lipid Deposition; Mechanistic Target of Rapamycin (mTOR); Rabbit Adipose-derived Stem Cells;
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1 Weibel ER. Stereological techniques for electron microscopic morphometry. In: Hayat MA, editor. Principles and techniques of electron microscopy, biological application. New York, USA: Van Nostrand Rheinhold; 1973. pp. 237-96.
2 Wang XJ, Liu L, Zhao JP, Jiao HC, Lin H. Stress impairs the reproduction of laying hens: an involvement of energy. World Poult Sci J 2017;73:845-56. https://doi.org/10.1017/S0043933917000794   DOI
3 Fu CY, Liu L, Gao Q, Sui XY, Li FC. Cloning, molecular characterization, and spatial and developmental expression analysis of GPR41 and GPR43 genes in New Zealand rabbits. Animal 2017;11:1798-806. https://doi.org/10.1017/S175173111700043X   DOI
4 Marques C, Oliveira CS, Alves S, et al. Acetate-induced apoptosis in colorectal carcinoma cells involves lysosomal membrane permeabilization and cathepsin D release. Cell Death Dis 2013;4:e507. https://doi.org/10.1038/cddis.2013.29   DOI
5 Liu L, Fu CY, Li FC. Acetate affects the process of lipid metabolism in rabbit liver, skeletal muscle and adipose tissue. Animals 2019;9:799. https://doi.org/10.3390/ani9100799   DOI
6 Li G, Yao W, Jiang H. Short-chain fatty acids enhance adipocyte differentiation in the stromal vascular fraction of porcine adipose tissue. J Nutr 2014;144:1887-95. https://doi.org/10.3945/jn.114.198531   DOI
7 Weitkunat K, Stuhlmann C, Postel A, et al. Short-chain fatty acids and inulin, but not guar gum, prevent diet-induced obesity and insulin resistance through differential mechanisms in mice. Sci Rep 2017;7:6109. https://doi.org/10.1038/s41598-017-06447-x   DOI
8 Shimobayashi M, Hall MN. Making new contacts: the mTOR network in metabolism and signalling crosstalk. Nat Rev Mol Cell Biol 2014;15:155-62. https://doi.org/10.1038/nrm3757   DOI
9 Cho HJ, Park J, Lee HW, Lee YS, Kim JB. Regulation of adipocyte differentiation and insulin action with rapamycin. Biochem Biophys Res Commun 2004;321:942-8. https://doi.org/10.1016/j.bbrc.2004.07.050   DOI
10 Tanabe J, Yamamoto DJ, Sutton B, et al. Effects of alcohol and acetate on cerebral blood flow: a pilot study. Alcohol Clin Exp Res 2019;43:2070-8. https://doi.org/10.1111/acer.14173   DOI
11 Kraemer FB, Shen WJ. Hormone-sensitive lipase knockouts. Nutr Metab 2006;3:12. https://doi.org/10.1186/1743-7075-3-12   DOI
12 Greenberg AS, Shen WJ, Muliro K, et al. Stimulation of lipolysis and hormone-sensitive lipase via the extracellular signal-regulated kinase pathway. J Biol Chem 2001;276:45456-61. https://doi.org/10.1074/jbc.M104436200   DOI
13 Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell 2012;149:274-93. https://doi.org/10.1016/j.cell.2012.03.017   DOI
14 Kimura I, Inoue D, Hirano K, Tsujimoto G. The SCFA receptor GPR43 and energy metabolism. Front Endocrinol 2014;5:85. https://doi.org/10.3389/fendo.2014.00085   DOI
15 Liu L, Fu C, Li FC. Dietary niacin supplementation suppressed hepatic lipid accumulation in rabbits. Asian-Australas J Anim Sci 2016;29:1748-55. https://doi.org/10.5713/ajas.15.0824   DOI
16 Zhang YY, Zhu SZ, Wang XP, Wang CY, Li FC. The effect of dietary selenium levels on growth performance, antioxidant capacity and glutathione peroxidase 1 (GSHPx1) mRNA expression in growing meat rabbits. Anim Feed Sci Technol 2011;169:259-64. https://doi.org/10.1016/j.anifeedsci.2011.07.006   DOI
17 Liu L, Xu S, Wang X, Jiao H, Lin H. Peripheral insulin doesn't alter appetite of broiler chicks. Asian-Australas J Anim Sci 2016;29:1294-9. https://doi.org/10.5713/ajas.15.0674   DOI
18 Liu L, Zhao XY, Liu YX, Zhao H, Li FC. Dietary addition of garlic straw improved the intestinal barrier in rabbits. J Anim Sci 2019;97:4248-55. https://doi.org/10.1093/jas/skz277   DOI
19 Polak P, Cybulski N, Feige JN, Auwerx J, Ruegg MA, Hall MN. Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration. Cell Metab 2008;8:399-410. https://doi.org/10.1016/j.cmet.2008.09.003   DOI
20 Liu DD, Han CC, Wan HF, et al. Effects of inhibiting PI3KAkt-mTOR pathway on lipid metabolism homeostasis in goose primary hepatocytes. Animal 2016;10:1319-27. https://doi.org/10.1017/S1751731116000380   DOI
21 Skiba-Cassy S, Lansard M, Panserat S, Medale F. Rainbow trout genetically selected for greater muscle fat content display increased activation of liver TOR signaling and lipogenic gene expression. Am J Physiol Regul Integr Comp Physiol 2009;297:1421-9. https://doi.org/10.1152/ajpregu.00312.2009   DOI
22 Gu W, Song L, Li XM, Wang D, Guo XJ, Xu WG. Mesenchymal stem cells alleviate airway inflammation and emphysema in COPD through down-regulation of cyclooxygenase-2 via p38 and ERK MAPK pathways. Sci Rep 2015;5:8733. https://doi.org/10.1038/srep08733   DOI
23 Yu W, Chen Z, Zhang J, et al. Critical role of phosphoinositide 3-kinase cascade in adipogenesis of human mesenchymal stem cells. Mol Cell Biochem 2008;310:11-8. https://doi.org/10.1007/s11010-007-9661-9   DOI
24 Rumberger JM, Arch JR, Green A. Butyrate and other shortchain fatty acids increase the rate of lipolysis in 3T3-L1 adipocytes. Peer J 2014;2:e611. https://doi.org/10.7717/peerj.611   DOI
25 Liu J, Zheng L, Zhong J, Wu N, Liu G, Lin X. Oleanolic acid induces protective autophagy in cancer cells through the JNK and mTOR pathways. Oncol Rep 2014;32:567-72. https://doi.org/10.3892/or.2014.3239   DOI
26 Chen PL, Riley DJ, Chen Y, Lee WH. Retinoblastoma protein positively regulates terminal adipocyte differentiation through direct interaction with C/EBPs. Genes Dev 1996;10:2794-804.   DOI
27 Zhang T, Sawada K, Yamamoto N, Ashida H. 4-Hydroxyderricin and xanthoangelol from Ashitaba (Angelica keiskei) suppress differentiation of preadiopocytes to adipocytes via AMPK and MAPK pathways. Mol Nutr Food Res 2013;57: 1729-40. https://doi.org/10.1002/mnfr.201300020   DOI
28 Tang QQ, Otto TC, Lane MD. Mitotic clonal expansion: a synchronous process required for adipogenesis. Proc Natl Acad Sci USA 2003;100:44-9. https://doi.org/10.1073/pnas. 0137044100   DOI
29 Prusty D, Park BH, Davis KE, Farmer SR. Activation of MEK/ ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARgamma) and C/EBPalpha gene expression during the differentiation of 3T3-L1 preadipocytes. J Biol Chem 2002;277:46226-32. https://doi.org/10.1074/jbc.M207776200   DOI
30 Hong YH, Nishimura Y, Hishikawa D, et al. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology 2005;146:5092-9. https://doi.org/10.1210/en.2005-0545   DOI
31 Gagnon A, Lau S, Sorisky A. Rapamycin-sensitive phase of 3T3-L1 preadipocyte differentiation after clonal expansion. J Cell Physiol 2001;189:14-22. https://doi.org/10.1002/jcp.1132   DOI
32 Camp HS, Tafuri SR. Regulation of peroxisome proliferatoractivated receptor gamma activity by mitogen-activated protein kinase. J Biol Chem 1997;272:10811-6. https://doi.org/10.1074/jbc.272.16.10811   DOI
33 Ge H, Li X, Weiszmann J, et al. Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Endocrinology 2008; 149:4519-26. https://doi.org/10.1210/en.2008-0059   DOI
34 Uehara T, Tokumitsu Y, Nomura Y. Wortmannin inhibits insulin-induced ras and mitogen-activated protein kinase activation related to adipocyte differentiation in 3T3-L1 fibroblasts. Biochem Biophys Res Commun 1995;210:574-80. https://doi.org/10.1006/bbrc.1995.1698   DOI
35 Zhu YL, Wang CY, Wang XP, Li B, Sun LZ, Li FC. Effects of dietary fiber and starch levels on the non-specific immune response of growing rabbits. Livest Sci 2013;155:285-93. https://doi.org/10.1016/j.livsci.2013.04.018   DOI
36 Liu L, Liu H, Fu C, Li C, Li F. Acetate induces anorexia via up-regulating the hypothalamic pro-opiomelanocortin (POMC) gene expression in rabbits. J Anim Feed Sci 2017; 26:266-73. https://doi.org/10.22358/jafs/75979/2017   DOI
37 Zambell KL, Fitch MD, Fleming SE. Acetate and butyrate are the major substrates for de novo lipogenesis in rat colonic epithelial cells. J Nutr 2003;133:3509-15. https://doi.org/10.1093/jn/133.11.3509   DOI
38 Fu C, Liu L, Li F. Acetate alters the process of lipid metabolism in rabbits. Animal 2018;12:1895-902. https://doi.org/10.1017/S1751731117003275   DOI
39 Siersbaek R, Nielsen R, Mandrup S. PPARgamma in adipocyte differentiation and metabolism--novel insights from genomewide studies. FEBS Lett 2010;584:3242-9. https://doi.org/10.1016/j.febslet.2010.06.010   DOI
40 Engelman JA, Lisanti MP, Scherer PE. Specific inhibitors of p38 mitogen- activated protein kinase block 3T3-L1 adipogenesis. J Biol Chem 1998;273:32111-20. https://doi.org/10.1074/jbc.273.48.32111   DOI
41 Liu L, Fu CY, Liu YX, Li FC. Acetate stimulates lipogenesis via AMPKα signaling in rabbit adipose-derived stem cells. Gen Comp Endocr 2021;303:113715. https://doi.org/10.1016/j.ygcen.2021.113715   DOI