Generic placeholder image

Current Molecular Medicine


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

Research Article

Apolipoprotein A1 Inhibits Adipogenesis Progression of Human Adipose-Derived Mesenchymal Stem Cells

Author(s): Xin Su, Bin Wang*, Min Lai, Hua Peng, Jingjin Song, Huaibin Huang, Xiang Chen and Ye Cheng

Volume 23, Issue 8, 2023

Published on: 26 August, 2022

Page: [762 - 773] Pages: 12

DOI: 10.2174/1566524022666220607085908

Price: $65


Background: According to the reports, the most vital characteristic of obesity is an aberrant accumulation of triglycerides (TG) in the adipocyte. On the other hand, circulating concentrations of apolipoprotein A1 (apoA1) have been demonstrated to be strongly correlated with the prevalence and the pathological development of obesity. Nevertheless, the underlying mechanisms whereby apoA1 modulates the pathogenesis of obesity is still not fully elucidated.

Methods: Adipose-derived mesenchymal stem cells (AMSCs, isolated from the hospitalized patients were combined with 15 μg/ml recombined human apoA1 protein. The effects of apoA1 on modulating the intracellular levels of TG and the expression contents of adipogenic related cytokines were also analyzed. Furthermore, whether apoA1 modulated the adipogenesis progression via sortilin was also explored in the current research.

Results: During the adipogenesis progression, apoA1 could significantly lower the quantity of intracellular lipid droplets (LDs). Meanwhile, apoA1 could decrease the intracellular levels of TG and down-regulate the expression contents of several vital adipogenic related cytokines, such as CCAAT enhancer-binding proteins α/β (C/EBPα/β), fatty acid synthetase (FAS), and fatty acid-binding protein 4 (FABP4). Moreover, the inhibitory effect of apoA1 was further verified to be induced through upregulating the SORT1 gene expression which subsequently increased sortilin protein. Consistent with these findings, silencing the SORT1 gene expression could induce the loss-of-function (LOF) of apoA1 in modulating the adipogenesis progression of AMSCs.

Conclusion: In conclusion, apoA1 could suppress the adipogenesis progression of human AMSCs through, at least partly, up-regulating the SORT1 gene expression which subsequently increases the sortilin protein content. Thereby, the present research sheds light on a novel pathogenic mechanism by which apoA1 regulates adipogenesis progression and proposes that apoA1 embraces the function to treat obesity in clinical practice.

Keywords: Apolipoprotein A1, sortilin, inhibit, up-regulate, adipose-derived mesenchymal stem cell, adipogenesis progression.

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.
[] [PMID: 23279260]
Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism 2019; 92: 6-10.
[] [PMID: 30253139]
Su X, Peng D. The exchangeable apolipoproteins in lipid metabolism and obesity. Clin Chim Acta 2020; 503: 128-35.
[] [PMID: 31981585]
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.
[] [PMID: 28901468]
Rosenson RS, Brewer HB Jr, Ansell BJ, et al. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat Rev Cardiol 2016; 13(1): 48-60.
[] [PMID: 26323267]
Barrett TJ, Distel E, Murphy AJ, et al. Apolipoprotein AI) Promotes Atherosclerosis Regression in Diabetic Mice by Suppressing Myelopoiesis and Plaque Inflammation. Circulation 2019; 140(14): 1170-84.
[] [PMID: 31567014]
Smith JD. Apolipoprotein A-I and its mimetics for the treatment of atherosclerosis. Curr Opin Investig Drugs 2010; 11(9): 989-96.
[PMID: 20730693]
Xu LB, Zhou YF, Yao JL, et al. Apolipoprotein A1 polymorphisms and risk of coronary artery disease: A meta-analysis. Arch Med Sci 2017; 13(4): 813-9.
[] [PMID: 28721149]
Yang S, Yin RX, Miao L, Zhang QH, Zhou YG, Wu J. Association of CPS1 rs1047891 SNP and serum lipid levels in two Chinese ethnic groups. Int J Clin Exp Pathol 2018; 11(5): 2887-900.
[PMID: 31938413]
Ruan X, Li Z, Zhang Y, et al. Apolipoprotein A-I possesses an anti-obesity effect associated with increase of energy expenditure and up-regulation of UCP1 in brown fat. J Cell Mol Med 2011; 15(4): 763-72.
[] [PMID: 20193037]
Wei H, Averill MM, McMillen TS, et al. Modulation of adipose tissue lipolysis and body weight by high-density lipoproteins in mice. Nutr Diabetes 2014; 4(2): e108.
[] [PMID: 24567123]
Talbot H, Saada S, Naves T, Gallet PF, Fauchais AL, Jauberteau MO. Regulatory roles of sortilin and SorLA in immune-related processes. Front Pharmacol 2019; 9: 1507.
[] [PMID: 30666202]
Rabinowich L, Fishman S, Hubel E, et al. Sortilin deficiency improves the metabolic phenotype and reduces hepatic steatosis of mice subjected to diet-induced obesity. J Hepatol 2015; 62(1): 175-81.
[] [PMID: 25173968]
Su X, Peng D. New insight into sortilin in controlling lipid metabolism and the risk of atherogenesis. Biol Rev Camb Philos Soc 2019.
[PMID: 31625271]
Gauthier B, Robb M, McPherson R. Cholesteryl ester transfer protein gene expression during differentiation of human preadipocytes to adipocytes in primary culture. Atherosclerosis 1999; 142(2): 301-7.
[] [PMID: 10030381]
Kardassis D, Mosialou I, Kanaki M, Tiniakou I, Thymiakou E. Metabolism of HDL and its regulation. Curr Med Chem 2014; 21(25): 2864-80.
[] [PMID: 24606515]
Tian M, Li R, Shan Z, Wang DW, Jiang J, Cui G. Comparison of apolipoprotein B/A1 ratio, Framingham risk score and TC/HDL-c for predicting clinical outcomes in patients undergoing percutaneous coronary intervention. Lipids Health Dis 2019; 18(1): 202.
[] [PMID: 31744496]
Feingold KR, Grunfeld C. Effect of inflammation on HDL structure and function. Curr Opin Lipidol 2016; 27(5): 521-30.
[] [PMID: 27495134]
Sorci-Thomas MG, Thomas MJ. Microdomains, inflammation, and atherosclerosis. Circ Res 2016; 118(4): 679-91.
[] [PMID: 26892966]
Chen ES, Mazzotti DR, Furuya TK, et al. Apolipoprotein A1 gene polymorphisms as risk factors for hypertension and obesity. Clin Exp Med 2009; 9(4): 319-25.
[] [PMID: 19408098]
Zhang T, Chen J, Tang X, Luo Q, Xu D, Yu B. Interaction between adipocytes and high-density lipoprotein: New insights into the mechanism of obesity-induced dyslipidemia and atherosclerosis. Lipids Health Dis 2019; 18(1): 223.
[] [PMID: 31842884]
Wang C, Zhang M, Wu J, et al. The effect and mechanism of TLR9/KLF4 in FFA-induced adipocyte inflammation. Mediators Inflamm 2018; (2018): 6313484.
Wang S, Moustaid-Moussa N, Chen L, et al. Novel insights of dietary polyphenols and obesity. J Nutr Biochem 2014; 25(1): 1-18.
[] [PMID: 24314860]
Viktorinova A, Jurkovicova I, Fabryova L, et al. Abnormalities in the relationship of paraoxonase 1 with HDL and apolipoprotein A1 and their possible connection to HDL dysfunctionality in type 2 diabetes. Diabetes Res Clin Pract 2018; 140: 174-82.
[] [PMID: 29626583]
Contois J, McNamara JR, Lammi-Keefe C, Wilson PW, Massov T, Schaefer EJ. Reference intervals for plasma apolipoprotein A-1 determined with a standardized commercial immunoturbidimetric assay: Results from the Framingham Offspring study. Clin Chem 1996; 42(4): 507-14.
[] [PMID: 8605666]
Hosseini-Esfahani F, Mirmiran P, Daneshpour MS, et al. Dietary patterns interact with APOA1/APOC3 polymorphisms to alter the risk of the metabolic syndrome: The Tehran lipid and glucose study. Br J Nutr 2015; 113(4): 644-53.
[] [PMID: 25653052]
Ren D, Xu JH, Bi Y, et al. Association study between LEPR, MC4R polymorphisms and overweight/obesity in Chinese Han adolescents. Gene 2019; 692: 54-9.
[] [PMID: 30641221]
Lindahl M, Petrlova J, Dalla-Riva J, et al. ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation. J Lipid Res 2015; 56(12): 2248-59.
[] [PMID: 26504176]
Vanella L, Li M, Kim D, et al. ApoA1: Mimetic peptide reverses adipocyte dysfunction in vivo and in vitro via an increase in Heme Oxygenase (HO-1) and Wnt10b. Cell Cycle 2012; 11(4): 706-14.
[] [PMID: 22306989]
Ali AT, Hochfeld WE, Myburgh R, Pepper MS. Adipocyte and adipogenesis. Eur J Cell Biol 2013; 92(6-7): 229-36.
[] [PMID: 23876739]
Guo L, Li X, Tang QQ. Transcriptional regulation of adipocyte differentiation: A central role for CCAAT/enhancer-binding protein (C/EBP) β. J Biol Chem 2015; 290(2): 755-61.
[] [PMID: 25451943]
Garin-Shkolnik T, Rudich A, Hotamisligil GS, Rubinstein M. FABP4 attenuates PPARγ and adipogenesis and is inversely correlated with PPARγ in adipose tissues. Diabetes 2014; 63(3): 900-11.
[] [PMID: 24319114]
Moseti D, Regassa A, Kim WK. Molecular regulation of adipogenesis and potential anti-adipogenic bioactive molecules. Int J Mol Sci 2016; 17(1): E124.
[] [PMID: 26797605]
Gao A, Cayabyab FS, Chen X, et al. Implications of sortilin in lipid metabolism and lipid disorder diseases. DNA Cell Biol 2017; 36(12): 1050-61.
[] [PMID: 28945101]
Breitling C, Gross A, Büttner P, et al. Genetic contribution of variants near SORT1 and APOE on LDL cholesterol independent of obesity in children. PLoS One 2015; 10(9): e0138064.
[] [PMID: 26375028]
Kuçi S, Kuçi Z, Schäfer R, et al. Molecular signature of human bone marrow-derived mesenchymal stromal cell subsets. Sci Rep 2019; 9(1): 1774.
[] [PMID: 30742027]
Li J, Chen C, Li Y, et al. Inhibition of insulin/PI3K/AKT signaling decreases adipose Sortilin 1 in mice and 3T3-L1 adipocytes. Biochim Biophys Acta Mol Basis Dis 2017; 1863(11): 2924-33.
[] [PMID: 28844948]
Fenech M, Gavrilovic J, Turner J. Effect of tissue inhibitor of metalloproteinases 3 on DLK1 shedding in cultured human pre-adipocytes and implications for adipose tissue remodelling. Lancet 2015; 385 (Suppl. 1): S35.
[] [PMID: 26312857]
Mitterberger MC, Lechner S, Mattesich M, et al. DLK1(PREF1) is a negative regulator of adipogenesis in CD105+/CD90+/CD34+/CD31-/FABP4- adipose-derived stromal cells from subcutaneous abdominal fat pats of adult women. Stem Cell Res 2012; 9(1): 35-48.
[] [PMID: 22640926]

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