{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:56:56Z","timestamp":1762102616807,"version":"3.37.3"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T00:00:00Z","timestamp":1616198400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T00:00:00Z","timestamp":1616198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007049","name":"Korea Institute of Ocean Science and Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003566","name":"Ministry of Oceans and Fisheries","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003566","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Amino Acids"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\u03b1-Poly<jats:sc>-l-<\/jats:sc>lysine (PLL) has been used for various purposes such as cell attachment, immunization, and molecular delivery, and is known to be cytotoxic to several cell lines. Here, we studied the effect of PLL on the adipogenesis of 3T3-L1 cells and investigated the underlying mechanism. Differentiation media containing PLL with a molecular weight (MW) greater than 4\u00a0kDa enhanced lipid droplet formation and increased adipogenic marker levels, indicating an increase in adipocyte differentiation. PLL with a molecular weight between 30 and 70\u00a0kDa was more effective than PLL of other sizes in 3T3-L1 cell differentiation. Moreover, PLL induced 3T3-L1 adipogenesis in insulin-free adipocyte differentiation medium. Incubation with insulin and PLL exhibited greater adipogenesis than insulin treatment only even at a high concentration. PLL stimulated insulin signaling and augmented the signaling pathway when it was added with insulin. While PLL did not activate the glucocorticoid receptor, which is phosphorylated by dexamethasone (DEX), it showed a positive effect on the cAMP signal pathway when preadipocytes were treated with PLL and 3-isobutyl-1-methylxanthine (IBMX). Consistent with these results, incubation with PLL and DEX without IBMX induced adipocyte differentiation. We also observed that the mitotic clonal expansion phase was the critical stage in adipogenesis for inducing the effects of PLL. These results suggest that PLL functions as an adipogenic inducer in 3T3-L1 preadipocytes and PLL has a direct effect on insulin signaling, one of the main regulatory pathways.<\/jats:p>","DOI":"10.1007\/s00726-020-02932-2","type":"journal-article","created":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T08:02:18Z","timestamp":1616227338000},"page":"587-596","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["\u03b1-Poly-l-lysine functions as an adipogenic inducer in 3T3-L1 preadipocytes"],"prefix":"10.1007","volume":"53","author":[{"given":"Kyeong Won","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Jun","family":"An","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Hyun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4820-856X","authenticated-orcid":false,"given":"Hyung-Soon","family":"Yim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,20]]},"reference":[{"issue":"7","key":"2932_CR1","doi-asserted-by":"publisher","first-page":"1974","DOI":"10.1021\/bi00381a029","volume":"26","author":"MD Bazzi","year":"1987","unstructured":"Bazzi MD, Nelsestuen GL (1987) Role of substrate in imparting calcium and phospholipid requirements to protein kinase C activation. Biochemistry 26(7):1974\u20131982","journal-title":"Biochemistry"},{"issue":"2","key":"2932_CR2","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/0014-4827(80)90504-2","volume":"129","author":"JE Bottenstein","year":"1980","unstructured":"Bottenstein JE, Sato GH (1980) Fibronectin and polylysine requirement for proliferation of neuroblastoma cells in defined medium. Exp Cell Res 129(2):361\u2013366","journal-title":"Exp Cell Res"},{"issue":"2","key":"2932_CR3","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/0014-5793(85)80395-1","volume":"188","author":"AM Brunati","year":"1985","unstructured":"Brunati AM, Marchiori F, Pinna LA (1985) Isolation and partial characterization of distinct forms of tyrosine protein kinases from rat spleen. FEBS Lett 188(2):321\u2013325","journal-title":"FEBS Lett"},{"issue":"4\u20135","key":"2932_CR4","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.cytogfr.2005.04.004","volume":"16","author":"A Denley","year":"2005","unstructured":"Denley A, Cosgrove LJ, Booker GW, Wallace JC, Forbes BE (2005) Molecular interactions of the IGF system. Cytokine Growth Factor Rev 16(4\u20135):421\u2013439. https:\/\/doi.org\/10.1016\/j.cytogfr.2005.04.004","journal-title":"Cytokine Growth Factor Rev"},{"issue":"7","key":"2932_CR5","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/S0142-9612(02)00445-3","volume":"24","author":"D Fischer","year":"2003","unstructured":"Fischer D, Li Y, Ahlemeyer B, Krieglstein J, Kissel T (2003) In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials 24(7):1121\u20131131","journal-title":"Biomaterials"},{"key":"2932_CR6","doi-asserted-by":"publisher","unstructured":"Fujita-Yamaguchi Y, Sacks DB, McDonald JM, Sahal D, Kathuria S (1989) Effect of basic polycations and proteins on purified insulin receptor. Insulin-independent activation of the receptor tyrosine-specific protein kinase by poly(L-lysine). Biochem J 263 (3):813\u2013822. https:\/\/doi.org\/10.1042\/bj2630813","DOI":"10.1042\/bj2630813"},{"issue":"2","key":"2932_CR7","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1073\/pnas.84.2.324","volume":"84","author":"M Gatica","year":"1987","unstructured":"Gatica M, Allende CC, Antonelli M, Allende JE (1987) Polylysine-containing peptides, including the carboxyl-terminal segment of the human c-Ki-ras 2 protein, affect the activity of some key membrane enzymes. Proc Natl Acad Sci U S A 84(2):324\u2013328. https:\/\/doi.org\/10.1073\/pnas.84.2.324","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2932_CR8","doi-asserted-by":"crossref","unstructured":"Green H, Kehinde O (1975) An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell 5(1):19\u201327","DOI":"10.1016\/0092-8674(75)90087-2"},{"issue":"1","key":"2932_CR9","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/nchembio.1961","volume":"12","author":"CR Green","year":"2016","unstructured":"Green CR, Wallace M, Divakaruni AS, Phillips SA, Murphy AN, Ciaraldi TP, Metallo CM (2016) Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis. Nat Chem Biol 12(1):15\u201321. https:\/\/doi.org\/10.1038\/nchembio.1961","journal-title":"Nat Chem Biol"},{"issue":"2","key":"2932_CR10","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1074\/jbc.R114.619957","volume":"290","author":"L Guo","year":"2015","unstructured":"Guo L, Li X, Tang QQ (2015) Transcriptional regulation of adipocyte differentiation: a central role for CCAAT\/enhancer-binding protein (C\/EBP) beta. J Biol Chem 290(2):755\u2013761. https:\/\/doi.org\/10.1074\/jbc.R114.619957","journal-title":"J Biol Chem"},{"key":"2932_CR11","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/S0076-6879(79)58126-9","volume":"58","author":"RG Ham","year":"1979","unstructured":"Ham RG, McKeehan WL (1979) Media and growth requirements. Methods Enzymol 58:44\u201393","journal-title":"Methods Enzymol"},{"issue":"9492","key":"2932_CR12","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1016\/S0140-6736(05)67483-1","volume":"366","author":"DW Haslam","year":"2005","unstructured":"Haslam DW, James WP (2005) Obesity. Lancet 366(9492):1197\u20131209. https:\/\/doi.org\/10.1016\/S0140-6736(05)67483-1","journal-title":"Lancet"},{"issue":"2","key":"2932_CR13","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/S0273-2300(03)00029-1","volume":"37","author":"J Hiraki","year":"2003","unstructured":"Hiraki J, Ichikawa T, Ninomiya S, Seki H, Uohama K, Seki H, Kimura S, Yanagimoto Y, Barnett JW Jr (2003) Use of ADME studies to confirm the safety of epsilon-polylysine as a preservative in food. Regul Toxicol Pharmacol 37(2):328\u2013340","journal-title":"Regul Toxicol Pharmacol"},{"issue":"4","key":"2932_CR14","first-page":"367","volume":"28","author":"JKS Ho Kwon","year":"2001","unstructured":"Ho Kwon JKS, Rhie JW, Cho YN, Lim JS, Chung SH, Ahn ST (2001) The effect of poly-L-lysine on proliferation and differentiation of preadipocyte in the alginate gels. Arch Plast Surg 28(4):367\u2013372","journal-title":"Arch Plast Surg"},{"key":"2932_CR15","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.jconrel.2015.06.021","volume":"213","author":"Y Jiang","year":"2015","unstructured":"Jiang Y, Brynskikh AM et al (2015) SOD1 nanozyme salvages ischemic brain by locally protecting cerebral vasculature. J Control Release 213:36\u201344. https:\/\/doi.org\/10.1016\/j.jconrel.2015.06.021","journal-title":"J Control Release"},{"key":"2932_CR16","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jconrel.2016.02.038","volume":"231","author":"Y Jiang","year":"2016","unstructured":"Jiang Y, Arounleut P, Rheiner S, Bae Y, Kabanov AV, Milligan C, Manickam DS (2016) SOD1 nanozyme with reduced toxicity and MPS accumulation. J Control Release 231:38\u201349. https:\/\/doi.org\/10.1016\/j.jconrel.2016.02.038","journal-title":"J Control Release"},{"issue":"3","key":"2932_CR17","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.jconrel.2013.01.019","volume":"169","author":"Z Kadlecova","year":"2013","unstructured":"Kadlecova Z, Rajendra Y, Matasci M, Baldi L, Hacker DL, Wurm FM, Klok HA (2013) DNA delivery with hyperbranched polylysine: a comparative study with linear and dendritic polylysine. J Control Release 169(3):276\u2013288. https:\/\/doi.org\/10.1016\/j.jconrel.2013.01.019","journal-title":"J Control Release"},{"issue":"3","key":"2932_CR18","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1073\/pnas.84.3.648","volume":"84","author":"M Lemaitre","year":"1987","unstructured":"Lemaitre M, Bayard B, Lebleu B (1987) Specific antiviral activity of a poly(l-lysine)-conjugated oligodeoxyribonucleotide sequence complementary to vesicular stomatitis virus N protein mRNA initiation site. Proc Natl Acad Sci U S A 84(3):648\u2013652. https:\/\/doi.org\/10.1073\/pnas.84.3.648","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"2932_CR19","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/0304-4165(86)90285-0","volume":"883","author":"Y Manabe","year":"1986","unstructured":"Manabe Y, Longley C, Furmanski P (1986) High-level conjugation of chelating agents onto immunoglobulins: use of an intermediary poly(l-lysine)-diethylenetriaminepentaacetic acid carrier. Biochim Biophys Acta 883(3):460\u2013467","journal-title":"Biochim Biophys Acta"},{"key":"2932_CR20","doi-asserted-by":"publisher","unstructured":"Mazia D, Schatten G, Sale W (1975) Adhesion of cells to surfaces coated with polylysine. Applications to electron microscopy. J Cell Biol 66(1):198\u2013200. https:\/\/doi.org\/10.1083\/jcb.66.1.198","DOI":"10.1083\/jcb.66.1.198"},{"issue":"4","key":"2932_CR21","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.addr.2006.03.007","volume":"58","author":"TG Park","year":"2006","unstructured":"Park TG, Jeong JH, Kim SW (2006) Current status of polymeric gene delivery systems. Adv Drug Deliv Rev 58(4):467\u2013486. https:\/\/doi.org\/10.1016\/j.addr.2006.03.007","journal-title":"Adv Drug Deliv Rev"},{"key":"2932_CR22","doi-asserted-by":"crossref","unstructured":"Pelech S, Cohen P (1985) The protein phosphatases involved in cellular regulation. 1. Modulation of protein phosphatases-1 and 2A by histone H1, protamine, polylysine and heparin. Eur J Biochem 148(2):245\u2013251","DOI":"10.1111\/j.1432-1033.1985.tb08832.x"},{"issue":"11","key":"2932_CR23","doi-asserted-by":"publisher","first-page":"3804","DOI":"10.1128\/MCB.00709-07","volume":"28","author":"RK Petersen","year":"2008","unstructured":"Petersen RK, Madsen L, Pedersen LM, Hallenborg P, Hagland H, Viste K, Doskeland SO, Kristiansen K (2008) Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes. Mol Cell Biol 28(11):3804\u20133816. https:\/\/doi.org\/10.1128\/MCB.00709-07","journal-title":"Mol Cell Biol"},{"issue":"2","key":"2932_CR24","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/0014-5793(88)80858-5","volume":"231","author":"OM Rosen","year":"1988","unstructured":"Rosen OM, Lebwohl DE (1988) Polylysine activates and alters the divalent cation requirements of the insulin receptor protein tyrosine kinase. FEBS Lett 231(2):397\u2013401","journal-title":"FEBS Lett"},{"issue":"7121","key":"2932_CR25","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1038\/nature05483","volume":"444","author":"ED Rosen","year":"2006","unstructured":"Rosen ED, Spiegelman BM (2006) Adipocytes as regulators of energy balance and glucose homeostasis. Nature 444(7121):847\u2013853. https:\/\/doi.org\/10.1038\/nature05483","journal-title":"Nature"},{"issue":"9","key":"2932_CR26","doi-asserted-by":"publisher","first-page":"a008417","DOI":"10.1101\/cshperspect.a008417","volume":"4","author":"K Sarjeant","year":"2012","unstructured":"Sarjeant K, Stephens JM (2012) Adipogenesis. Cold Spring Harb Perspect Biol 4(9):a008417. https:\/\/doi.org\/10.1101\/cshperspect.a008417","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"19","key":"2932_CR27","doi-asserted-by":"publisher","first-page":"9402","DOI":"10.1016\/S0021-9258(19)76555-7","volume":"263","author":"PJ Smith","year":"1988","unstructured":"Smith PJ, Wise LS, Berkowitz R, Wan C, Rubin CS (1988) Insulin-like growth factor-I is an essential regulator of the differentiation of 3T3-L1 adipocytes. J Biol Chem 263(19):9402\u20139408","journal-title":"J Biol Chem"},{"issue":"6","key":"2932_CR28","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1053\/j.gastro.2007.09.005","volume":"133","author":"DH Song","year":"2007","unstructured":"Song DH, Getty-Kaushik L, Tseng E, Simon J, Corkey BE, Wolfe MM (2007) Glucose-dependent insulinotropic polypeptide enhances adipocyte development and glucose uptake in part through Akt activation. Gastroenterology 133(6):1796\u20131805. https:\/\/doi.org\/10.1053\/j.gastro.2007.09.005","journal-title":"Gastroenterology"},{"issue":"1","key":"2932_CR29","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1073\/pnas.0137044100","volume":"100","author":"QQ Tang","year":"2003","unstructured":"Tang QQ, Otto TC, Lane MD (2003) Mitotic clonal expansion: a synchronous process required for adipogenesis. Proc Natl Acad Sci U S A 100(1):44\u201349. https:\/\/doi.org\/10.1073\/pnas.0137044100","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2932_CR30","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.exer.2018.05.004","volume":"173","author":"S Vidhya","year":"2018","unstructured":"Vidhya S, Ramya R, Coral K, Sulochana KN, Bharathidevi SR (2018) Free amino acids hydroxyproline, lysine, and glycine promote differentiation of retinal pericytes to adipocytes: a protective role against proliferative diabetic retinopathy. Exp Eye Res 173:179\u2013187. https:\/\/doi.org\/10.1016\/j.exer.2018.05.004","journal-title":"Exp Eye Res"},{"issue":"6","key":"2932_CR31","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.3892\/ijmm.2013.1350","volume":"31","author":"J Yang","year":"2013","unstructured":"Yang J, Ren J, Song J, Liu F, Wu C, Wang X, Gong L, Li W, Xiao F, Yan F, Hou X, Chen L (2013) Glucagon-like peptide 1 regulates adipogenesis in 3T3-L1 preadipocytes. Int J Mol Med 31(6):1429\u20131435. https:\/\/doi.org\/10.3892\/ijmm.2013.1350","journal-title":"Int J Mol Med"}],"container-title":["Amino Acids"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00726-020-02932-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00726-020-02932-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00726-020-02932-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T17:07:25Z","timestamp":1620580045000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00726-020-02932-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,20]]},"references-count":31,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["2932"],"URL":"https:\/\/doi.org\/10.1007\/s00726-020-02932-2","relation":{},"ISSN":["0939-4451","1438-2199"],"issn-type":[{"type":"print","value":"0939-4451"},{"type":"electronic","value":"1438-2199"}],"subject":[],"published":{"date-parts":[[2021,3,20]]},"assertion":[{"value":"3 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This article does not contain any studies with human participants or animals performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}