Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

New Insights into Apolipoprotein A5 and the Modulation of Human Adipose-derived Mesenchymal Stem Cells Adipogenesis

Author(s): Xin Su, Shuwei Weng and Daoquan Peng*

Volume 20, Issue 2, 2020

Page: [144 - 156] Pages: 13

DOI: 10.2174/1566524019666190927155702

Price: $65

Abstract

Background: The hallmark of obesity is the excessive accumulation of triglyceride (TG) in adipose tissue. Apolipoprotein A5 (ApoA5) has been shown to influence the prevalence and pathogenesis of obesity. However, the underlying mechanisms remain to be clarified.

Methods: Human adipose-derived mesenchymal stem cells (AMSCs) were treated with 600 ng/ml human recombinant ApoA5 protein. The effect of ApoA5 on intracellular TG content and adipogenic related factors expression were determined. Furthermore, the effect of ApoA5 on CIDE-C expression was also observed.

Results: During the process of adipogenesis, ApoA5 treatment reduced the intracellular accumulation of lipid droplets and the TG levels; meanwhile, ApoA5 down-regulated the expression levels of adipogenic related factors, including CCAAT enhancer-binding proteins α/β (C/EBPα/β), fatty acid synthetase (FAS), and fatty acid-binding protein 4 (FABP4). Furthermore, the suppression of adipogenesis by ApoA5 was mediated through the inhibition of CIDE-C expression, an important factor which promotes the process of adipogenesis. However, over-expressing intracellular CIDE-C could lead to the loss-of-function of ApoA5 in inhibiting AMSCs adipogenesis.

Conclusions: In conclusion, ApoA5 inhibits the adipogenic process of AMSCs through, at least partly, down-regulating CIDE-C expression. The present study provides novel mechanisms whereby ApoA5 prevents obesity via AMSCs in humans.

Keywords: Apolipoprotein A5, CIDE-C, adipose-derived mesenchymal stem cells, adipogenesis, inhibit, AMSCs.

« Previous Next »
[1]
Su X, Kong Y, Peng DQ. New insights into apolipoprotein A5 in controlling lipoprotein metabolism in obesity and the metabolic syndrome patients. Lipids Health Dis 2018; 17(1): 174.
[http://dx.doi.org/10.1186/s12944-018-0833-2] [PMID: 30053818]
[2]
Poston L, Caleyachetty R, Cnattingius S, et al. Preconceptional and maternal obesity: Epidemiology and health consequences. Lancet Diabetes Endocrinol 2016; 4(12): 1025-36.
[http://dx.doi.org/10.1016/S2213-8587(16)30217-0] [PMID: 27743975]
[3]
Wu CL, Zhao SP, Yu BL. Intracellular role of exchangeable apolipoproteins in energy homeostasis, obesity and non-alcoholic fatty liver disease. Biol Rev Camb Philos Soc 2015; 90(2): 367-76.
[http://dx.doi.org/10.1111/brv.12116] [PMID: 24834836]
[4]
Tang M, Chen R, Wang H, et al. Obesity-induced methylation of osteopontin contributes to adipogenic differentiation of adipose-derived mesenchymal stem cells. Stem Cells Int 2019; 20191238153
[http://dx.doi.org/10.1155/2019/1238153] [PMID: 30911298]
[5]
Debnath T, Chelluri LK. Standardization and quality assessment for clinical grade mesenchymal stem cells from human adipose tissue. Hematol Transfus Cell Ther 2019; 41(1): 7-16.
[http://dx.doi.org/10.1016/j.htct.2018.05.001] [PMID: 30793099]
[6]
Sabol RA, Bowles AC, Côté A, et al. Leptin produced by obesity-altered adipose stem cells promotes metastasis but not tumorigenesis of triple-negative breast cancer in orthotopic xenograft and patient-derived xenograft models. Breast Cancer Res 2019; 21(1): 67.
[http://dx.doi.org/10.1186/s13058-019-1153-9] [PMID: 31118047]
[7]
Elosua R, Ordovas JM, Cupples LA, et al. Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: The Framingham Study. J Lipid Res 2006; 47(5): 990-6.
[http://dx.doi.org/10.1194/jlr.M500446-JLR200] [PMID: 16474174]
[8]
Zhao SP, Hu S, Li J, et al. Association of human serum apolipoprotein A5 with lipid profiles affected by gender. Clin Chim Acta 2007; 376(1-2): 68-71.
[http://dx.doi.org/10.1016/j.cca.2006.07.014] [PMID: 16962087]
[9]
Huang XS, Zhao SP, Hu M, Bai L, Zhang Q, Zhao W. Decreased apolipoprotein A5 is implicated in insulin resistance-related hypertriglyceridemia in obesity. Atherosclerosis 2010; 210(2): 563-8.
[http://dx.doi.org/10.1016/j.atherosclerosis.2009.12.004] [PMID: 20047745]
[10]
Jakel H, Nowak M, Moitrot E, et al. The liver X receptor ligand T0901317 down-regulates APOA5 gene expression through activation of SREBP-1c. J Biol Chem 2004; 279(44): 45462-9.
[http://dx.doi.org/10.1074/jbc.M404744200] [PMID: 15317819]
[11]
Kluger M, Heeren J, Merkel M. Apoprotein A-V: an important regulator of triglyceride metabolism. J Inherit Metab Dis 2008; 31(2): 281-8.
[http://dx.doi.org/10.1007/s10545-008-0863-4] [PMID: 18415697]
[12]
Feng Q, Baker SS, Liu W, et al. Increased apolipoprotein A5 expression in human and rat non-alcoholic fatty livers. Pathology 2015; 47(4): 341-8.
[http://dx.doi.org/10.1097/PAT.0000000000000251] [PMID: 25938357]
[13]
Zheng XY, Zhao SP, Yu BL, Wu CL, Liu L. Apolipoprotein A5 internalized by human adipocytes modulates cellular triglyceride content. Biol Chem 2012; 393(3): 161-7.
[http://dx.doi.org/10.1515/hsz-2011-0259] [PMID: 22718631]
[14]
Ito M, Nagasawa M, Omae N, Ide T, Akasaka Y, Murakami K. Differential regulation of CIDEA and CIDEC expression by insulin via Akt1/2- and JNK2-dependent pathways in human adipocytes. J Lipid Res 2011; 52(8): 1450-60.
[http://dx.doi.org/10.1194/jlr.M012427] [PMID: 21636835]
[15]
Nishino N, Tamori Y, Tateya S, et al. FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets. J Clin Invest 2008; 118(8): 2808-21.
[http://dx.doi.org/10.1172/JCI34090] [PMID: 18654663]
[16]
Jambunathan S, Yin J, Khan W, Tamori Y, Puri V. FSP27 promotes lipid droplet clustering and then fusion to regulate triglyceride accumulation. PLoS One 2011; 6(12)e28614
[http://dx.doi.org/10.1371/journal.pone.0028614] [PMID: 22194867]
[17]
Nishimoto Y, Nakajima S, Tateya S, Saito M, Ogawa W, Tamori Y. Cell death-inducing DNA fragmentation factor A-like effector A and fat-specific protein 27β coordinately control lipid droplet size in brown adipocytes. J Biol Chem 2017; 292(26): 10824-34.
[http://dx.doi.org/10.1074/jbc.M116.768820] [PMID: 28490632]
[18]
Puri V, Ranjit S, Konda S, et al. Cidea is associated with lipid droplets and insulin sensitivity in humans. Proc Natl Acad Sci USA 2008; 105(22): 7833-8.
[http://dx.doi.org/10.1073/pnas.0802063105] [PMID: 18509062]
[19]
Puri V. Fasting regulates FSP27 expression in the liver. J Lipid Res 2013; 54(3): 569-70.
[http://dx.doi.org/10.1194/jlr.E036020] [PMID: 23335806]
[20]
Bociąga-Jasik M, Polus A, Góralska J, et al. Metabolic effects of the HIV protease inhibitor--saquinavir in differentiating human preadipocytes. Pharmacol Rep 2013; 65(4): 937-50.
[http://dx.doi.org/10.1016/S1734-1140(13)71075-2] [PMID: 24145088]
[21]
Zheng XY, Yu BL, Xie YF, Zhao SP, Wu CL. Apolipoprotein A5 regulates intracellular triglyceride metabolism in adipocytes. Mol Med Rep 2017; 16(5): 6771-9.
[http://dx.doi.org/10.3892/mmr.2017.7461] [PMID: 28901468]
[22]
Zhu WF, Wang CL, Liang L, et al. Triglyceride-raising APOA5 genetic variants are associated with obesity and non-HDL-C in Chinese children and adolescents. Lipids Health Dis 2014; 13: 93.
[http://dx.doi.org/10.1186/1476-511X-13-93] [PMID: 24903888]
[23]
Zheng XY, Zhao SP, Yan H. The role of apolipoprotein A5 in obesity and the metabolic syndrome. Biol Rev Camb Philos Soc 2013; 88(2): 490-8.
[http://dx.doi.org/10.1111/brv.12005] [PMID: 23279260]
[24]
Niculescu LS, Fruchart-Najib J, Fruchart JC, Sima A. Apolipoprotein A-V gene polymorphisms in subjects with metabolic syndrome. Clin Chem Lab Med 2007; 45(9): 1133-9.
[http://dx.doi.org/10.1515/CCLM.2007.257] [PMID: 17635078]
[25]
Zhao SP, Li R, Dai W, Yu BL, Chen LZ, Huang XS. Xuezhikang contributes to greater triglyceride reduction than simvastatin in hypertriglyceridemia rats by up-regulating apolipoprotein A5 via the PPARα signaling pathway. PLoS One 2017; 12(9)e0184949
[http://dx.doi.org/10.1371/journal.pone.0184949] [PMID: 28934253]
[26]
Li HX, Luo X, Liu RX, Yang YJ, Yang GS. Roles of Wnt/beta-catenin signaling in adipogenic differentiation potential of adipose-derived mesenchymal stem cells. Mol Cell Endocrinol 2008; 291(1-2): 116-24.
[http://dx.doi.org/10.1016/j.mce.2008.05.005] [PMID: 18584948]
[27]
Chen J, Bao C, Kim JT, Cho JS, Qiu S, Lee HJ. Sulforaphene inhibition of adipogenesis via hedgehog signaling in 3T3-L1 adipocytes. J Agric Food Chem 2018; 66(45): 11926-34.
[http://dx.doi.org/10.1021/acs.jafc.8b04330] [PMID: 30354116]
[28]
Smith A, Yu X, Yin L. Diazinon exposure activated transcriptional factors CCAAT-enhancer-binding proteins α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) and induced adipogenesis in 3T3-L1 preadipocytes. Pestic Biochem Physiol 2018; 150: 48-58.
[http://dx.doi.org/10.1016/j.pestbp.2018.07.003] [PMID: 30195387]
[29]
Cho YL, Min JK, Roh KM, et al. Phosphoprotein phosphatase 1CB (PPP1CB), a novel adipogenic activator, promotes 3T3-L1 adipogenesis. Biochem Biophys Res Commun 2015; 467(2): 211-7.
[http://dx.doi.org/10.1016/j.bbrc.2015.10.004] [PMID: 26449462]
[30]
Xu L, Zhou L, Li P. CIDE proteins and lipid metabolism. Arterioscler Thromb Vasc Biol 2012; 32(5): 1094-8.
[http://dx.doi.org/10.1161/ATVBAHA.111.241489] [PMID: 22517368]
[31]
Zhou L, Park SY, Xu L, et al. Insulin resistance and white adipose tissue inflammation are uncoupled in energetically challenged Fsp27-deficient mice. Nat Commun 2015; 6: 5949.
[http://dx.doi.org/10.1038/ncomms6949] [PMID: 25565658]
[32]
Vilà-Brau A, De Sousa-Coelho AL, Gonçalves JF, Haro D, Marrero PF. Fsp27/CIDEC is a CREB target gene induced during early fasting in liver and regulated by FA oxidation rate. J Lipid Res 2013; 54(3): 592-601.
[http://dx.doi.org/10.1194/jlr.M028472] [PMID: 23220584]
[33]
Qian H, Chen Y, Nian Z, et al. HDAC6-mediated acetylation of lipid droplet-binding protein CIDEC regulates fat-induced lipid storage. J Clin Invest 2017; 127(4): 1353-69.
[http://dx.doi.org/10.1172/JCI85963] [PMID: 28287402]
[34]
Matsuo K, Matsusue K, Aibara D, Takiguchi S, Gonzalez FJ, Yamano S. Insulin represses fasting-induced expression of hepatic fat-specific protein 27. Biol Pharm Bull 2017; 40(6): 888-93.
[http://dx.doi.org/10.1248/bpb.b17-00105] [PMID: 28566630]
[35]
Samuels JS, Shashidharamurthy R, Rayalam S. Novel anti-obesity effects of beer hops compound xanthohumol: role of AMPK signaling pathway. Nutr Metab (Lond) 2018; 15: 42.
[http://dx.doi.org/10.1186/s12986-018-0277-8] [PMID: 29946343]
[36]
Reynés B, García-Ruiz E, Oliver P, Palou A. Gene expression of peripheral blood mononuclear cells is affected by cold exposure. Am J Physiol Regul Integr Comp Physiol 2015; 309(8): R824-34.
[http://dx.doi.org/10.1152/ajpregu.00221.2015] [PMID: 26246506]
[37]
García-Ruiz E, Reynés B, Díaz-Rúa R, Ceresi E, Oliver P, Palou A. The intake of high-fat diets induces the acquisition of brown adipocyte gene expression features in white adipose tissue. Int J Obes 2015; 39(11): 1619-29.
[http://dx.doi.org/10.1038/ijo.2015.112] [PMID: 26063331]
[38]
Koo SY, Hwang JH, Yang SH, et al. Anti-obesity effect of standardized extract of microalga Phaeodactylum tricornutum containing fucoxanthin. Mar Drugs 2019; 17(5)E311
[http://dx.doi.org/10.3390/md17050311] [PMID: 31137922]
[39]
Fang D, Shi X, Lu T, Ruan H, Gao Y. The glycoprotein follistatin-like 1 promotes brown adipose thermogenesis. Metabolism 2019; 98: 16-26.
[http://dx.doi.org/10.1016/j.metabol.2019.05.008] [PMID: 31132382]
[40]
Sánchez-Moreno C, Ordovás JM, Smith CE, Baraza JC, Lee YC, Garaulet M. APOA5 gene variation interacts with dietary fat intake to modulate obesity and circulating triglycerides in a Mediterranean population. J Nutr 2011; 141(3): 380-5.
[http://dx.doi.org/10.3945/jn.110.130344] [PMID: 21209257]
[41]
Kisfali P, Mohás M, Maász A, et al. Haplotype analysis of the apolipoprotein A5 gene in patients with the metabolic syndrome. Nutr Metab Cardiovasc Dis 2010; 20(7): 505-11.
[http://dx.doi.org/10.1016/j.numecd.2009.05.001] [PMID: 19692219]

Rights & Permissions Print Cite
Article Metrics
12
© 2024 Bentham Science Publishers | Privacy Policy