Adipokines in the Skin and in Dermatological Diseases

Dóra Kovács, Fruzsina Fazekas, Attila Oláh, Dániel Törőcsik, Dóra Kovács, Fruzsina Fazekas, Attila Oláh, Dániel Törőcsik

Abstract

Adipokines are the primary mediators of adipose tissue-induced and regulated systemic inflammatory diseases; however, recent findings revealed that serum levels of various adipokines correlate also with the onset and the severity of dermatological diseases. Importantly, further data confirmed that the skin serves not only as a target for adipokine signaling, but may serve as a source too. In this review, we aim to provide a complex overview on how adipokines may integrate into the (patho) physiological conditions of the skin by introducing the cell types, such as keratinocytes, fibroblasts, and sebocytes, which are known to produce adipokines as well as the signals that target them. Moreover, we discuss data from in vivo and in vitro murine and human studies as well as genetic data on how adipokines may contribute to various aspects of the homeostasis of the skin, e.g., melanogenesis, hair growth, or wound healing, just as to the pathogenesis of dermatological diseases such as psoriasis, atopic dermatitis, acne, rosacea, and melanoma.

Keywords: acne; adipokines; atopic dermatitis; fibroblasts; hair growth; keratinocytes; melanocytes; melanoma; psoriasis; sebocytes.

Conflict of interest statement

A.O. provides consultancy services to Botanix Pharmaceuticals Ltd., a pharmaceutical company pioneering in the dermatological use of phytocannabinoids. Botanix Pharmaceuticals Ltd. or the above founding sponsors had no role in the writing of the manuscript, or in the decision to publish it. Thus, the authors declare no relevant conflict of interest.

Figures

Figure 1
Figure 1
Overview of adipokines expressed and secreted by different human skin cell types and their effects on these cells.
Figure 2
Figure 2
Adipokines might be involved in the pathogenesis of psoriasis vulgaris. Note the simplified characteristic histopathological findings in psoriasis skin: hyperproliferation of keratinocytes (1), elongation of the dermal papillae (2), dilated blood vessels (3) and immune cell infiltration in the dermis (4). Hematoxylin eosin staining; original magnification: 50×.
Figure 3
Figure 3
Adipokines might be involved in the pathogenesis of atopic dermatitis. Note the simplified characteristic histopathological findings in AD skin: slight epidermal hyperplasia with impaired barrier function (1) and immune cell infiltration in the dermis (2). Hematoxylin eosin staining; original magnification: 50×.
Figure 4
Figure 4
Adipokines might be involved in the pathogenesis of acne vulgaris. Note the simplified characteristic histopathological findings in acne: ductal hyperkeratosis (1), altered sebum production by sebocytes (2) and immune cell infiltration in the dermis (3). Hematoxylin eosin staining; original magnification: 50×.
Figure 5
Figure 5
Adipokines may be involved in the pathogenesis of rosacea. Note the simplified characteristic histopathological findings in rosacea: impaired barrier function (1), interfollicular inflammation in the dermis (2). Hematoxylin eosin staining; original magnification: 50×.
Figure 6
Figure 6
Adipokines might be involved in the pathogenesis of malignant melanoma. Note the simplified characteristic histopathological findings in melanoma: invasion of the malignant cells (1), increased vascularization (2) and immune cell infiltration (3). Hematoxylin eosin staining; original magnification: 50×.

References

    1. Stolarczyk E. Adipose tissue inflammation in obesity: A metabolic or immune response? Curr. Opin. Pharmacol. 2017;37:35–40. doi: 10.1016/j.coph.2017.08.006.
    1. Mittal B. Subcutaneous adipose tissue & visceral adipose tissue. Indian J. Med. Res. 2019;149:571–573. doi: 10.4103/ijmr.IJMR_1910_18.
    1. Ibrahim M.M. Subcutaneous and visceral adipose tissue: Structural and functional differences. Obes. Rev. Off. J. Int. Assoc. Study Obes. 2010;11:11–18. doi: 10.1111/j.1467-789X.2009.00623.x.
    1. Fasshauer M., Bluher M. Adipokines in health and disease. Trends Pharmacol. Sci. 2015;36:461–470. doi: 10.1016/j.tips.2015.04.014.
    1. Reilly S.M., Saltiel A.R. Adapting to obesity with adipose tissue inflammation. Nat. Rev. Endocrinol. 2017;13:633–643. doi: 10.1038/nrendo.2017.90.
    1. Hotamisligil G.S. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017;542:177–185. doi: 10.1038/nature21363.
    1. Atawia R.T., Bunch K.L., Toque H.A., Caldwell R.B., Caldwell R.W. Mechanisms of obesity-induced metabolic and vascular dysfunctions. Front. Biosci. (Landmark Ed.) 2019;24:890–934.
    1. Jialal I., Devaraj S. Subcutaneous adipose tissue biology in metabolic syndrome. Horm. Mol. Biol. Clin. Investig. 2018;33 doi: 10.1515/hmbci-2017-0074.
    1. Burhans M.S., Hagman D.K., Kuzma J.N., Schmidt K.A., Kratz M. Contribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus. Compr. Physiol. 2018;9:1–58. doi: 10.1002/cphy.c170040.
    1. Giralt M., Cereijo R., Villarroya F. Adipokines and the Endocrine Role of Adipose Tissues. Handb. Exp. Pharmacol. 2016;233:265–282. doi: 10.1007/164_2015_6.
    1. Raucci R., Rusolo F., Sharma A., Colonna G., Castello G., Costantini S. Functional and structural features of adipokine family. Cytokine. 2013;61:1–14. doi: 10.1016/j.cyto.2012.08.036.
    1. Gonçalves N., Falcão-Pires I., Leite-Moreira A.F. Adipokines and their receptors: Potential new targets in cardiovascular diseases. Future Med. Chem. 2015;7:139–157. doi: 10.4155/fmc.14.147.
    1. Gorska E., Popko K., Stelmaszczyk-Emmel A., Ciepiela O., Kucharska A., Wasik M. Leptin receptors. Eur. J. Med. Res. 2010;15(Suppl. 2):50–54. doi: 10.1186/2047-783X-15-S2-50.
    1. Banas M., Zegar A., Kwitniewski M., Zabieglo K., Marczynska J., Kapinska-Mrowiecka M., LaJevic M., Zabel B.A., Cichy J. The expression and regulation of chemerin in the epidermis. PLoS ONE. 2015;10:e0117830. doi: 10.1371/journal.pone.0117830.
    1. Deshmane S.L., Kremlev S., Amini S., Sawaya B.E. Monocyte chemoattractant protein-1 (MCP-1): An overview. J. Interferon Cytokine Res. Off. J. Int. Soc. Interferon Cytokine Res. 2009;29:313–326. doi: 10.1089/jir.2008.0027.
    1. Wysocka M.B., Pietraszek-Gremplewicz K., Nowak D. The Role of Apelin in Cardiovascular Diseases, Obesity and Cancer. Front. Physiol. 2018;9:557. doi: 10.3389/fphys.2018.00557.
    1. Park H.K., Kwak M.K., Kim H.J., Ahima R.S. Linking resistin, inflammation, and cardiometabolic diseases. Korean J. Intern. Med. 2017;32:239–247. doi: 10.3904/kjim.2016.229.
    1. Romacho T., Valencia I., Ramos-González M., Vallejo S., López-Esteban M., Lorenzo O., Cannata P., Romero A., San Hipólito-Luengo A., Gómez-Cerezo J.F., et al. Visfatin/eNampt induces endothelial dysfunction in vivo: A role for Toll-Like Receptor 4 and NLRP3 inflammasome. Sci. Rep. 2020;10:5386. doi: 10.1038/s41598-020-62190-w.
    1. Trepanowski J.F., Mey J., Varady K.A. Fetuin-A: A novel link between obesity and related complications. Int. J. Obes. 2015;39:734–741. doi: 10.1038/ijo.2014.203.
    1. Tanabe H., Fujii Y., Okada-Iwabu M., Iwabu M., Nakamura Y., Hosaka T., Motoyama K., Ikeda M., Wakiyama M., Terada T., et al. Crystal structures of the human adiponectin receptors. Nature. 2015;520:312–316. doi: 10.1038/nature14301.
    1. Ceperuelo-Mallafre V., Ejarque M., Duran X., Pachon G., Vazquez-Carballo A., Roche K., Nunez-Roa C., Garrido-Sanchez L., Tinahones F.J., Vendrell J., et al. Zinc-alpha2-Glycoprotein Modulates AKT-Dependent Insulin Signaling in Human Adipocytes by Activation of the PP2A Phosphatase. PLoS ONE. 2015;10:e0129644. doi: 10.1371/journal.pone.0129644.
    1. Rahman F.A., Krause M.P. PAI-1, the Plasminogen System, and Skeletal Muscle. Int. J. Mol. Sci. 2020;21:7066. doi: 10.3390/ijms21197066.
    1. Langelueddecke C., Roussa E., Fenton R.A., Thévenod F. Expression and function of the lipocalin-2 (24p3/NGAL) receptor in rodent and human intestinal epithelia. PLoS ONE. 2013;8:e71586. doi: 10.1371/journal.pone.0071586.
    1. Zhou Y., Zhang B., Hao C., Huang X., Li X., Huang Y., Luo Z. Omentin-A Novel Adipokine in Respiratory Diseases. Int. J. Mol. Sci. 2017;19:73. doi: 10.3390/ijms19010073.
    1. Zhang Y., Chua S., Jr. Leptin Function and Regulation. Compr. Physiol. 2017;8:351–369. doi: 10.1002/cphy.c160041.
    1. Mancuso P. The role of adipokines in chronic inflammation. Immunotargets Ther. 2016;5:47–56. doi: 10.2147/ITT.S73223.
    1. Francisco V., Pino J., Gonzalez-Gay M.A., Mera A., Lago F., Gómez R., Mobasheri A., Gualillo O. Adipokines and inflammation: Is it a question of weight? Br. J. Pharmacol. 2018;175:1569–1579. doi: 10.1111/bph.14181.
    1. Wolk K., Sabat R. Adipokines in psoriasis: An important link between skin inflammation and metabolic alterations. Rev. Endocr. Metab. Disord. 2016;17:305–317. doi: 10.1007/s11154-016-9381-0.
    1. Lynch M., Ahern T., Sweeney C.M., Malara A., Tobin A.M., O’Shea D., Kirby B. Adipokines, psoriasis, systemic inflammation, and endothelial dysfunction. Int. J. Dermatol. 2017;56:1103–1118. doi: 10.1111/ijd.13699.
    1. Zhang Y., Proenca R., Maffei M., Barone M., Leopold L., Friedman J.M. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–432. doi: 10.1038/372425a0.
    1. Pan W.W., Myers M.G., Jr. Leptin and the maintenance of elevated body weight. Nat. Rev. Neurosci. 2018;19:95–105. doi: 10.1038/nrn.2017.168.
    1. Triantafyllou G.A., Paschou S.A., Mantzoros C.S. Leptin and Hormones: Energy Homeostasis. Endocrinol. Metab. Clin. 2016;45:633–645. doi: 10.1016/j.ecl.2016.04.012.
    1. Tong K.M., Shieh D.C., Chen C.P., Tzeng C.Y., Wang S.P., Huang K.C., Chiu Y.C., Fong Y.C., Tang C.H. Leptin induces IL-8 expression via leptin receptor, IRS-1, PI3K, Akt cascade and promotion of NF-kappaB/p300 binding in human synovial fibroblasts. Cell. Signal. 2008;20:1478–1488. doi: 10.1016/j.cellsig.2008.04.003.
    1. Palhinha L., Liechocki S., Hottz E.D., Pereira J., de Almeida C.J., Moraes-Vieira P.M.M., Bozza P.T., Maya-Monteiro C.M. Leptin Induces Proadipogenic and Proinflammatory Signaling in Adipocytes. Front. Endocrinol. 2019;10:841. doi: 10.3389/fendo.2019.00841.
    1. Poeggeler B., Schulz C., Pappolla M.A., Bodó E., Tiede S., Lehnert H., Paus R. Leptin and the skin: A new frontier. Exp. Dermatol. 2010;19:12–18. doi: 10.1111/j.1600-0625.2009.00930.x.
    1. Lee M., Lee E., Jin S.H., Ahn S., Kim S.O., Kim J., Choi D., Lim K.M., Lee S.T., Noh M. Leptin regulates the pro-inflammatory response in human epidermal keratinocytes. Arch. Dermatol. Res. 2018;310:351–362. doi: 10.1007/s00403-018-1821-0.
    1. Kanda N., Watanabe S. Leptin enhances human beta-defensin-2 production in human keratinocytes. Endocrinology. 2008;149:5189–5198. doi: 10.1210/en.2008-0343.
    1. Rico L., Del Rio M., Bravo A., Ramirez A., Jorcano J.L., Page M.A., Larcher F. Targeted overexpression of leptin to keratinocytes in transgenic mice results in lack of skin phenotype but induction of early leptin resistance. Endocrinology. 2005;146:4167–4176. doi: 10.1210/en.2005-0156.
    1. Samal B., Sun Y., Stearns G., Xie C., Suggs S., McNiece I. Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol. Cell Biol. 1994;14:1431–1437. doi: 10.1128/MCB.14.2.1431.
    1. Lee B.C., Song J., Lee A., Cho D., Kim T.S. Visfatin Promotes Wound Healing through the Activation of ERK1/2 and JNK1/2 Pathway. Int. J. Mol. Sci. 2018;19:3642. doi: 10.3390/ijms19113642.
    1. Kanda N., Hau C.S., Tada Y., Tatsuta A., Sato S., Watanabe S. Visfatin enhances CXCL8, CXCL10, and CCL20 production in human keratinocytes. Endocrinology. 2011;152:3155–3164. doi: 10.1210/en.2010-1481.
    1. Hau C.S., Kanda N., Noda S., Tatsuta A., Kamata M., Shibata S., Asano Y., Sato S., Watanabe S., Tada Y. Visfatin enhances the production of cathelicidin antimicrobial peptide, human beta-defensin-2, human beta-defensin-3, and S100A7 in human keratinocytes and their orthologs in murine imiquimod-induced psoriatic skin. Am. J. Pathol. 2013;182:1705–1717. doi: 10.1016/j.ajpath.2013.01.044.
    1. Managò A., Audrito V., Mazzola F., Sorci L. Extracellular nicotinate phosphoribosyltransferase binds Toll like receptor 4 and mediates inflammation. Nat. Commun. 2019;10:4116. doi: 10.1038/s41467-019-12055-2.
    1. Travelli C., Colombo G., Mola S., Genazzani A.A., Porta C. NAMPT: A pleiotropic modulator of monocytes and macrophages. Pharm. Res. 2018;135:25–36. doi: 10.1016/j.phrs.2018.06.022.
    1. La Manna G., Ghinatti G., Tazzari P.L., Alviano F., Ricci F., Capelli I., Cuna V., Todeschini P., Brunocilla E., Pagliaro P., et al. Neutrophil gelatinase-associated lipocalin increases HLA-G(+)/FoxP3(+) T-regulatory cell population in an in vitro model of PBMC. PLoS ONE. 2014;9:e89497. doi: 10.1371/journal.pone.0089497.
    1. Mallbris L., O’Brien K.P., Hulthén A., Sandstedt B., Cowland J.B., Borregaard N., Ståhle-Bäckdahl M. Neutrophil gelatinase-associated lipocalin is a marker for dysregulated keratinocyte differentiation in human skin. Exp. Dermatol. 2002;11:584–591. doi: 10.1034/j.1600-0625.2002.110611.x.
    1. Wolk K., Wenzel J., Tsaousi A., Witte-Händel E., Babel N., Zelenak C., Volk H.D., Sterry W., Schneider-Burrus S., Sabat R. Lipocalin-2 is expressed by activated granulocytes and keratinocytes in affected skin and reflects disease activity in acne inversa/hidradenitis suppurativa. Br. J. Dermatol. 2017;177:1385–1393. doi: 10.1111/bjd.15424.
    1. Shao S., Cao T., Jin L., Li B., Fang H., Zhang J., Zhang Y., Hu J., Wang G. Increased Lipocalin-2 Contributes to the Pathogenesis of Psoriasis by Modulating Neutrophil Chemotaxis and Cytokine Secretion. J. Investig. Dermatol. 2016;136:1418–1428. doi: 10.1016/j.jid.2016.03.002.
    1. Béke G., Dajnoki Z., Kapitány A., Gáspár K., Medgyesi B., Póliska S., Hendrik Z., Péter Z., Törőcsik D., Bíró T., et al. Immunotopographical Differences of Human Skin. Front. Immunol. 2018;9:424. doi: 10.3389/fimmu.2018.00424.
    1. Flevaris P., Vaughan D. The Role of Plasminogen Activator Inhibitor Type-1 in Fibrosis. Semin. Thromb. Hemost. 2017;43:169–177. doi: 10.1055/s-0036-1586228.
    1. Rømer J., Lund L.R., Eriksen J., Ralfkiaer E., Zeheb R., Gelehrter T.D., Danø K., Kristensen P. Differential expression of urokinase-type plasminogen activator and its type-1 inhibitor during healing of mouse skin wounds. J. Investig. Dermatol. 1991;97:803–811. doi: 10.1111/1523-1747.ep12486833.
    1. Lund L.R., Eriksen J., Ralfkiaer E., Rømer J. Differential expression of urokinase-type plasminogen activator, its receptor, and inhibitors in mouse skin after exposure to a tumor-promoting phorbol ester. J. Investig. Dermatol. 1996;106:622–630. doi: 10.1111/1523-1747.ep12345425.
    1. Jacenik D., Fichna J. Chemerin in immune response and gastrointestinal pathophysiology. Clin. Chim. Acta Int. J. Clin. Chem. 2020;504:146–153. doi: 10.1016/j.cca.2020.02.008.
    1. Wang Y., Huo J., Zhang D., Hu G., Zhang Y. Chemerin/ChemR23 axis triggers an inflammatory response in keratinocytes through ROS-sirt1-NF-kappaB signaling. J. Cell. Biochem. 2019;120:6459–6470. doi: 10.1002/jcb.27936.
    1. Dubois-Vedrenne I., De Henau O., Robert V., Langa F., Javary J., Al Delbany D., Vosters O., Angelats-Canals E., Vernimmen M., Luangsay S., et al. Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis. Front. Oncol. 2019;9:1253. doi: 10.3389/fonc.2019.01253.
    1. Guzik T.J., Skiba D.S., Touyz R.M., Harrison D.G. The role of infiltrating immune cells in dysfunctional adipose tissue. Cardiovasc. Res. 2017;113:1009–1023. doi: 10.1093/cvr/cvx108.
    1. Mai W., Lu D., Liu X., Chen L. MCP-1 produced by keratinocytes is associated with leucocyte recruitment during elicitation of nickel-induced occupational allergic contact dermatitis. Toxicol. Ind. Health. 2018;34:36–43. doi: 10.1177/0748233717738633.
    1. Li J., Farthing P.M., Thornhill M.H. Oral and skin keratinocytes are stimulated to secrete monocyte chemoattractant protein-1 by tumour necrosis factor-alpha and interferon-gamma. J. Oral Pathol. Med. Off. Publ. Int. Assoc. Oral Pathol. Am. Acad. Oral Pathol. 2000;29:438–444. doi: 10.1034/j.1600-0714.2000.290904.x.
    1. Giustizieri M.L., Mascia F., Frezzolini A., De Pità O., Chinni L.M., Giannetti A., Girolomoni G., Pastore S. Keratinocytes from patients with atopic dermatitis and psoriasis show a distinct chemokine production profile in response to T cell-derived cytokines. J. Allergy Clin. Immunol. 2001;107:871–877. doi: 10.1067/mai.2001.114707.
    1. Lee W.J., Jo S.Y., Lee M.H., Won C.H., Lee M.W., Choi J.H., Chang S.E. The Effect of MCP-1/CCR2 on the Proliferation and Senescence of Epidermal Constituent Cells in Solar Lentigo. Int. J. Mol. Sci. 2016;17:948. doi: 10.3390/ijms17060948.
    1. Yamashiro S., Takeya M., Kuratsu J., Ushio Y., Takahashi K., Yoshimura T. Intradermal injection of monocyte chemoattractant protein-1 induces emigration and differentiation of blood monocytes in rat skin. Int. Arch. Allergy Immunol. 1998;115:15–23. doi: 10.1159/000023825.
    1. Nakamura K., Williams I.R., Kupper T.S. Keratinocyte-derived monocyte chemoattractant protein 1 (MCP-1): Analysis in a transgenic model demonstrates MCP-1 can recruit dendritic and Langerhans cells to skin. J. Investig. Dermatol. 1995;105:635–643. doi: 10.1111/1523-1747.ep12324061.
    1. Huang X., Yang Z. Resistin’s, obesity and insulin resistance: The continuing disconnect between rodents and humans. J. Endocrinol. Investig. 2016;39:607–615. doi: 10.1007/s40618-015-0408-2.
    1. Harrison W.J., Bull J.J., Seltmann H., Zouboulis C.C., Philpott M.P. Expression of lipogenic factors galectin-12, resistin, SREBP-1, and SCD in human sebaceous glands and cultured sebocytes. J. Investig. Dermatol. 2007;127:1309–1317. doi: 10.1038/sj.jid.5700743.
    1. Kumar D., Lee B., Puan K.J., Lee W., Luis B.S., Yusof N., Andiappan A.K., Del Rosario R. Resistin expression in human monocytes is controlled by two linked promoter SNPs mediating NFKB p50/p50 binding and C-methylation. Sci. Rep. 2019;9:15245. doi: 10.1038/s41598-019-51592-0.
    1. Kelly M., Widjaja-Adhi M.A., Palczewski G., von Lintig J. Transport of vitamin A across blood-tissue barriers is facilitated by STRA6. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2016;30:2985–2995. doi: 10.1096/fj.201600446R.
    1. Skazik C., Amann P.M., Heise R., Marquardt Y., Czaja K., Kim A., Rühl R., Kurschat P., Merk H.F., Bickers D.R., et al. Downregulation of STRA6 expression in epidermal keratinocytes leads to hyperproliferation-associated differentiation in both in vitro and in vivo skin models. J. Investig. Dermatol. 2014;134:1579–1588. doi: 10.1038/jid.2013.507.
    1. Kidoya H., Naito H., Takakura N. Apelin induces enlarged and nonleaky blood vessels for functional recovery from ischemia. Blood. 2010;115:3166–3174. doi: 10.1182/blood-2009-07-232306.
    1. Lv S.Y., Cui B., Chen W.D., Wang Y.D. Apelin/APJ system: A key therapeutic target for liver disease. Oncotarget. 2017;8:112145–112151. doi: 10.18632/oncotarget.22841.
    1. Lee H.J., Lim Y., Yang S.J. Involvement of resveratrol in crosstalk between adipokine adiponectin and hepatokine fetuin-A in vivo and in vitro. J. Nutr. Biochem. 2015;26:1254–1260. doi: 10.1016/j.jnutbio.2015.06.001.
    1. Wang X.Q., Hung B.S., Kempf M., Liu P.Y., Dalley A.J., Saunders N.A., Kimble R.M. Fetuin-A promotes primary keratinocyte migration: Independent of epidermal growth factor receptor signalling. Exp. Dermatol. 2010;19:e289–e292. doi: 10.1111/j.1600-0625.2009.00978.x.
    1. Xiao X.H., Wang Y.D., Qi X.Y., Wang Y.Y., Li J.Y., Li H., Zhang P.Y., Liao H.L., Li M.H., Liao Z.Z., et al. Zinc alpha2 glycoprotein protects against obesity-induced hepatic steatosis. Int. J. Obes. 2018;42:1418–1430. doi: 10.1038/s41366-018-0151-9.
    1. Chen S.H., Arany I., Apisarnthanarax N., Rajaraman S., Tyring S.K., Horikoshi T., Brysk H., Brysk M.M. Response of keratinocytes from normal and psoriatic epidermis to interferon-gamma differs in the expression of zinc-alpha(2)-glycoprotein and cathepsin D. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2000;14:565–571. doi: 10.1096/fasebj.14.3.565.
    1. Wang Z.V., Scherer P.E. Adiponectin, the past two decades. J. Mol. Cell Biol. 2016;8:93–100. doi: 10.1093/jmcb/mjw011.
    1. Bjursell M., Ahnmark A., Bohlooly Y.M., William-Olsson L., Rhedin M., Peng X.R., Ploj K., Gerdin A.K., Arnerup G., Elmgren A., et al. Opposing effects of adiponectin receptors 1 and 2 on energy metabolism. Diabetes. 2007;56:583–593. doi: 10.2337/db06-1432.
    1. Ouchi N., Kihara S., Arita Y., Nishida M., Matsuyama A., Okamoto Y., Ishigami M., Kuriyama H., Kishida K., Nishizawa H., et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation. 2001;103:1057–1063. doi: 10.1161/01.CIR.103.8.1057.
    1. Yamaguchi N., Argueta J.G., Masuhiro Y., Kagishita M., Nonaka K., Saito T., Hanazawa S., Yamashita Y. Adiponectin inhibits Toll-like receptor family-induced signaling. FEBS Lett. 2005;579:6821–6826. doi: 10.1016/j.febslet.2005.11.019.
    1. Wolf A.M., Wolf D., Rumpold H., Enrich B., Tilg H. Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochem. Biophys. Res. Commun. 2004;323:630–635. doi: 10.1016/j.bbrc.2004.08.145.
    1. Won C.H., Yoo H.G., Park K.Y., Shin S.H., Park W.S., Park P.J., Chung J.H., Kwon O.S., Kim K.H. Hair growth-promoting effects of adiponectin in vitro. J. Investig. Dermatol. 2012;132:2849–2851. doi: 10.1038/jid.2012.217.
    1. Shibata S., Tada Y., Asano Y., Hau C.S., Kato T., Saeki H., Yamauchi T., Kubota N., Kadowaki T., Sato S. Adiponectin regulates cutaneous wound healing by promoting keratinocyte proliferation and migration via the ERK signaling pathway. J. Immunol. 2012;189:3231–3241. doi: 10.4049/jimmunol.1101739.
    1. Hong S.P., Seo H.S., Shin K.O., Park K., Park B.C., Kim M.H., Park M., Kim C.D., Seo S.J. Adiponectin Enhances Human Keratinocyte Lipid Synthesis via SIRT1 and Nuclear Hormone Receptor Signaling. J. Investig. Dermatol. 2019;139:573–582. doi: 10.1016/j.jid.2018.08.032.
    1. Kawai K., Kageyama A., Tsumano T., Nishimoto S., Fukuda K., Yokoyama S., Oguma T., Fujita K., Yoshimoto S., Yanai A., et al. Effects of adiponectin on growth and differentiation of human keratinocytes--implication of impaired wound healing in diabetes. Biochem. Biophys. Res. Commun. 2008;374:269–273. doi: 10.1016/j.bbrc.2008.07.045.
    1. Kim M., Park K.Y., Lee M.K., Jin T., Seo S.J. Adiponectin Suppresses UVB-Induced Premature Senescence and hBD2 Overexpression in Human Keratinocytes. PLoS ONE. 2016;11:e0161247. doi: 10.1371/journal.pone.0161247.
    1. Jin T., Park K.Y., Seo S.J. Adiponectin Upregulates Filaggrin Expression via SIRT1-Mediated Signaling in Human Normal Keratinocytes. Ann. Dermatol. 2017;29:407–413. doi: 10.5021/ad.2017.29.4.407.
    1. Zhang C., Zhu K.J., Liu J.L., Xu G.X., Liu W., Jiang F.X., Zheng H.F., Quan C. Omentin-1 plasma levels and omentin-1 expression are decreased in psoriatic lesions of psoriasis patients. Arch. Dermatol. Res. 2015;307:455–459. doi: 10.1007/s00403-015-1549-z.
    1. Saalbach A., Vester K., Rall K., Tremel J., Anderegg U., Beck-Sickinger A.G., Blüher M., Simon J.C. Vaspin--a link of obesity and psoriasis? Exp. Dermatol. 2012;21:309–312. doi: 10.1111/j.1600-0625.2012.01460.x.
    1. Saalbach A., Tremel J., Herbert D., Schwede K., Wandel E., Schirmer C., Anderegg U., Beck-Sickinger A.G., Heiker J.T., Schultz S., et al. Anti-Inflammatory Action of Keratinocyte-Derived Vaspin: Relevance for the Pathogenesis of Psoriasis. Am. J. Pathol. 2016;186:639–651. doi: 10.1016/j.ajpath.2015.10.030.
    1. Di Carlo S.E., Peduto L. The perivascular origin of pathological fibroblasts. J. Clin. Investig. 2018;128:54–63. doi: 10.1172/JCI93558.
    1. Chen J.H., Goh K.J., Rocha N., Groeneveld M.P. Evaluation of human dermal fibroblasts directly reprogrammed to adipocyte-like cells as a metabolic disease model. Dis. Models Mech. 2017;10:1411–1420. doi: 10.1242/dmm.030981.
    1. Glasow A., Kiess W., Anderegg U., Berthold A., Bottner A., Kratzsch J. Expression of leptin (Ob) and leptin receptor (Ob-R) in human fibroblasts: Regulation of leptin secretion by insulin. J. Clin. Endocrinol. Metab. 2001;86:4472–4479. doi: 10.1210/jcem.86.9.7792.
    1. Ambrosini G., Nath A.K., Sierra-Honigmann M.R., Flores-Riveros J. Transcriptional activation of the human leptin gene in response to hypoxia. Involvement of hypoxia-inducible factor 1. J. Biol. Chem. 2002;277:34601–34609. doi: 10.1074/jbc.M205172200.
    1. Ezure T., Amano S. Adiponectin and leptin up-regulate extracellular matrix production by dermal fibroblasts. Biofactors. 2007;31:229–236. doi: 10.1002/biof.5520310310.
    1. Luo L., Li J., Liu H., Jian X., Zou Q., Zhao Q., Le Q., Chen H., Gao X., He C. Adiponectin Is Involved in Connective Tissue Growth Factor-Induced Proliferation, Migration and Overproduction of the Extracellular Matrix in Keloid Fibroblasts. Int. J. Mol. Sci. 2017;18:1044. doi: 10.3390/ijms18051044.
    1. Fang C.L., Huang L.H., Tsai H.Y., Chang H.I. Dermal Lipogenesis Inhibits Adiponectin Production in Human Dermal Fibroblasts while Exogenous Adiponectin Administration Prevents against UVA-Induced Dermal Matrix Degradation in Human Skin. Int. J. Mol. Sci. 2016;17:1129. doi: 10.3390/ijms17071129.
    1. Fang F., Liu L., Yang Y., Tamaki Z., Wei J., Marangoni R.G., Bhattacharyya S., Summer R.S., Ye B., Varga J. The adipokine adiponectin has potent anti-fibrotic effects mediated via adenosine monophosphate-activated protein kinase: Novel target for fibrosis therapy. Arthritis Res. Ther. 2012;14:R229. doi: 10.1186/ar4070.
    1. Farsam V., Basu A., Gatzka M., Treiber N., Schneider L.A., Mulaw M.A., Lucas T., Kochanek S., Dummer R., Levesque M.P., et al. Senescent fibroblast-derived Chemerin promotes squamous cell carcinoma migration. Oncotarget. 2016;7:83554–83569. doi: 10.18632/oncotarget.13446.
    1. Yokoyama Y., Sekiguchi A., Fujiwara C., Uchiyama A., Uehara A., Ogino S., Torii R., Ishikawa O., Motegi S.I. Inhibitory Regulation of Skin Fibrosis in Systemic Sclerosis by Apelin/APJ Signaling. Arthritis Rheumatol. 2018;70:1661–1672. doi: 10.1002/art.40533.
    1. He Z., Ong C.H., Halper J., Bateman A. Progranulin is a mediator of the wound response. Nat. Med. 2003;9:225–229. doi: 10.1038/nm816.
    1. Zouboulis C.C., Picardo M., Ju Q., Kurokawa I., Törőcsik D., Bíró T., Schneider M.R. Beyond acne: Current aspects of sebaceous gland biology and function. Rev. Endocr. Metab. Disord. 2016;17:319–334. doi: 10.1007/s11154-016-9389-5.
    1. Nagy I., Pivarcsi A., Kis K., Koreck A., Bodai L., McDowell A., Seltmann H., Patrick S., Zouboulis C.C., Kemény L. Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines/chemokines in human sebocytes. Microbes Infect. 2006;8:2195–2205. doi: 10.1016/j.micinf.2006.04.001.
    1. Kovács D., Lovászi M., Póliska S., Oláh A. Sebocytes differentially express and secrete adipokines. Exp. Dermatol. 2016;25:194–199. doi: 10.1111/exd.12879.
    1. Törőcsik D., Kovács D., Camera E., Lovászi M., Cseri K., Nagy G.G., Molinaro R., Rühl R., Tax G., Szabó K., et al. Leptin promotes a proinflammatory lipid profile and induces inflammatory pathways in human SZ95 sebocytes. Br. J. Dermatol. 2014;171:1326–1335. doi: 10.1111/bjd.13229.
    1. Chen H.C., Smith S.J., Tow B., Elias P.M., Farese R.V., Jr. Leptin modulates the effects of acyl CoA:diacylglycerol acyltransferase deficiency on murine fur and sebaceous glands. J. Clin. Investig. 2002;109:175–181. doi: 10.1172/JCI0213880.
    1. Melnik B.C. Is sebocyte-derived leptin the missing link between hyperseborrhea, ductal hypoxia, inflammation and comedogenesis in acne vulgaris? Exp. Dermatol. 2016;25:181–182. doi: 10.1111/exd.12917.
    1. Jung Y.R., Lee J.H., Sohn K.C., Lee Y., Seo Y.J., Kim C.D., Lee J.H., Hong S.P., Seo S.J., Kim S.J., et al. Adiponectin Signaling Regulates Lipid Production in Human Sebocytes. PLoS ONE. 2017;12:e0169824. doi: 10.1371/journal.pone.0185081.
    1. D’Mello S.A., Finlay G.J., Baguley B.C., Askarian-Amiri M.E. Signaling Pathways in Melanogenesis. Int. J. Mol. Sci. 2016;17:1144. doi: 10.3390/ijms17071144.
    1. Morpurgo G., Fioretti B., Catacuzzeno L. The increased incidence of malignant melanoma in obese individuals is due to impaired melanogenesis and melanocyte DNA repair. Med. Hypotheses. 2012;78:533–535. doi: 10.1016/j.mehy.2012.01.028.
    1. Bang S., Won K.H., Moon H.R., Yoo H., Hong A., Song Y. Novel regulation of melanogenesis by adiponectin via the AMPK/CRTC pathway. Pigment Cell Melanoma Res. 2017;30:553–557. doi: 10.1111/pcmr.12596.
    1. Chung B.Y., Noh T.K., Yang S.H., Kim I.H., Lee M.W., Yoon T.J., Chang S.E. Gene expression profiling in melasma in Korean women. Dermatology. 2014;229:333–342. doi: 10.1159/000365080.
    1. Hale L.P. Zinc alpha-2-glycoprotein regulates melanin production by normal and malignant melanocytes. J. Investig. Dermatol. 2002;119:464–470. doi: 10.1046/j.1523-1747.2002.01813.x.
    1. Bagherani N. The Newest Hypothesis about Vitiligo: Most of the Suggested Pathogeneses of Vitiligo Can Be Attributed to Lack of One Factor, Zinc-alpha2-Glycoprotein. ISRN Dermatol. 2012;2012:405268. doi: 10.5402/2012/405268.
    1. El-Rifaie A., Gohary Y.M., Abd-El Aziz G.M., Owies F.O. Zinc-alpha2-Glycoprotein (ZAG): A New Deficiency in Vitiligo Patients. Skinmed. 2019;17:248–253.
    1. Saxena N., Mok K.W., Rendl M. An updated classification of hair follicle morphogenesis. Exp. Dermatol. 2019;28:332–344. doi: 10.1111/exd.13913.
    1. Oh J.W., Kloepper J., Langan E.A., Kim Y., Yeo J., Kim M.J., Hsi T.C., Rose C., Yoon G.S., Lee S.J., et al. A Guide to Studying Human Hair Follicle Cycling In Vivo. J. Investig. Dermatol. 2016;136:34–44. doi: 10.1038/JID.2015.354.
    1. Paus R., Langan E.A., Vidali S., Ramot Y., Andersen B. Neuroendocrinology of the hair follicle: Principles and clinical perspectives. Trends Mol. Med. 2014;20:559–570. doi: 10.1016/j.molmed.2014.06.002.
    1. Grymowicz M., Rudnicka E. Hormonal Effects on Hair Follicles. Int. J. Mol. Sci. 2020;21:5342. doi: 10.3390/ijms21155342.
    1. Tóth K.F., Ádám D. Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System. Molecules. 2019;24:918. doi: 10.3390/molecules24050918.
    1. Iguchi M., Aiba S., Yoshino Y., Tagami H. Human follicular papilla cells carry out nonadipose tissue production of leptin. J. Investig. Dermatol. 2001;117:1349–1356. doi: 10.1046/j.0022-202x.2001.01606.x.
    1. Sumikawa Y., Inui S., Nakajima T., Itami S. Hair cycle control by leptin as a new anagen inducer. Exp. Dermatol. 2014;23:27–32. doi: 10.1111/exd.12286.
    1. Tiede S., Kloepper J.E., Ernst N., Poeggeler B., Kruse C., Paus R. Nestin in human skin: Exclusive expression in intramesenchymal skin compartments and regulation by leptin. J. Investig. Dermatol. 2009;129:2711–2720. doi: 10.1038/jid.2009.148.
    1. Yang C.C., Sheu H.M., Chung P.L., Chang C.H., Tsai Y.S., Hughes M.W., Tuan T.L., Huang L.L. Leptin of dermal adipose tissue is differentially expressed during the hair cycle and contributes to adipocyte-mediated growth inhibition of anagen-phase vibrissa hair. Exp. Dermatol. 2015;24:57–60. doi: 10.1111/exd.12566.
    1. Foster A.R., Nicu C., Schneider M.R., Hinde E., Paus R. Dermal white adipose tissue undergoes major morphological changes during the spontaneous and induced murine hair follicle cycling: A reappraisal. Arch. Dermatol. Res. 2018;310:453–462. doi: 10.1007/s00403-018-1831-y.
    1. Harris R.B. Direct and indirect effects of leptin on adipocyte metabolism. Biochim. Biophys. Acta. 2014;1842:414–423. doi: 10.1016/j.bbadis.2013.05.009.
    1. Yang C.C., Chung P.L., Lin L.Y., Hughes M.W., Tsai Y.S. Higher plasma leptin is associated with higher risk of androgenetic alopecia in men. Exp. Dermatol. 2017;26:524–526. doi: 10.1111/exd.13369.
    1. Lyons-Giordano B., Lazarus G.S. Skin abnormalities in mice transgenic for plasminogen activator inhibitor 1: Implications for the regulation of desquamation and follicular neogenesis by plasminogen activator enzymes. Dev. Biol. 1995;170:289–298. doi: 10.1006/dbio.1995.1215.
    1. Kato M., Hasunuma N., Nakayama R., Takeda J., Itami S., Taira M., Manabe M., Osada S. Progranulin, a secreted tumorigenesis and dementia-related factor, regulates mouse hair growth. J. Dermatol. Sci. 2009;53:234–236. doi: 10.1016/j.jdermsci.2008.10.002.
    1. Incel-Uysal P., Akdogan N., Alli N., Oktem A., Candar T., Topcuoglu C., Turhan T. Assessment of Metabolic Profile and Ischemia-modified Albumin Level in Patients with Alopecia Areata: A Case-Control Study. Indian J. Dermatol. 2019;64:12–18. doi: 10.4103/ijd.IJD_238_18.
    1. Narla S., Azzam M., Townsend S., Vellaichamy G., Marzano A.V. Identifying key components and therapeutic targets of the immune system in hidradenitis suppurativa with an emphasis on neutrophils. Br. J. Dermatol. 2020 doi: 10.1111/bjd.19538.
    1. Stallmeyer B., Kämpfer H., Podda M., Kaufmann R., Pfeilschifter J., Frank S. A novel keratinocyte mitogen: Regulation of leptin and its functional receptor in skin repair. J. Investig. Dermatol. 2001;117:98–105. doi: 10.1046/j.0022-202x.2001.01387.x.
    1. Tadokoro S., Ide S., Tokuyama R., Umeki H., Tatehara S., Kataoka S., Satomura K. Leptin promotes wound healing in the skin. PLoS ONE. 2015;10:e0121242. doi: 10.1371/journal.pone.0121242.
    1. Frank S., Stallmeyer B., Kämpfer H., Kolb N., Pfeilschifter J. Leptin enhances wound re-epithelialization and constitutes a direct function of leptin in skin repair. J. Clin. Investig. 2000;106:501–509. doi: 10.1172/JCI9148.
    1. Murad A., Nath A.K., Cha S.T., Demir E., Flores-Riveros J., Sierra-Honigmann M.R. Leptin is an autocrine/paracrine regulator of wound healing. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2003;17:1895–1897. doi: 10.1096/fj.03-0068fje.
    1. Lerman O.Z., Galiano R.D., Armour M., Levine J.P., Gurtner G.C. Cellular dysfunction in the diabetic fibroblast: Impairment in migration, vascular endothelial growth factor production, and response to hypoxia. Am. J. Pathol. 2003;162:303–312. doi: 10.1016/S0002-9440(10)63821-7.
    1. Miao Q., Ku A.T., Nishino Y., Howard J.M., Rao A.S., Shaver T.M., Garcia G.E., Le D.N., Karlin K.L., Westbrook T.F., et al. Tcf3 promotes cell migration and wound repair through regulation of lipocalin 2. Nat. Commun. 2014;5:4088. doi: 10.1038/ncomms5088.
    1. Xu M., Zhang Y., Cheng H., Liu Y., Zou X., Zhan N., Xiao S., Xia Y. Transcription factor 7-like 1 dysregulates keratinocyte differentiation through upregulating lipocalin 2. Cell Death Discov. 2016;2:16028. doi: 10.1038/cddiscovery.2016.28.
    1. Fitsialos G., Chassot A.A., Turchi L., Dayem M.A., LeBrigand K., Moreilhon C., Meneguzzi G., Buscà R., Mari B., Barbry P., et al. Transcriptional signature of epidermal keratinocytes subjected to in vitro scratch wounding reveals selective roles for ERK1/2, p38, and phosphatidylinositol 3-kinase signaling pathways. J. Biol. Chem. 2007;282:15090–15102. doi: 10.1074/jbc.M606094200.
    1. Providence K.M., Higgins P.J. PAI-1 expression is required for epithelial cell migration in two distinct phases of in vitro wound repair. J. Cell. Physiol. 2004;200:297–308. doi: 10.1002/jcp.20016.
    1. Dipietro L.A., Reintjes M.G., Low Q.E., Levi B., Gamelli R.L. Modulation of macrophage recruitment into wounds by monocyte chemoattractant protein-1. Wound Repair Regen. Off. Publ. Wound Heal. Soc. Eur. Tissue Repair Soc. 2001;9:28–33. doi: 10.1046/j.1524-475x.2001.00028.x.
    1. Akazawa Y., Sayo T., Sugiyama Y., Sato T., Akimoto N., Ito A., Inoue S. Adiponectin resides in mouse skin and upregulates hyaluronan synthesis in dermal fibroblasts. Connect. Tissue Res. 2011;52:322–328. doi: 10.3109/03008207.2010.528566.
    1. Herédi E., Csordás A., Clemens M., Adám B., Gáspár K., Törőcsik D., Nagy G., Adány R., Gaál J., Remenyik E., et al. The prevalence of obesity is increased in patients with late compared with early onset psoriasis. Ann. Epidemiol. 2013;23:688–692. doi: 10.1016/j.annepidem.2013.08.006.
    1. Wong Y., Nakamizo S., Tan K.J., Kabashima K. An Update on the Role of Adipose Tissues in Psoriasis. Front. Immunol. 2019;10:1507. doi: 10.3389/fimmu.2019.01507.
    1. Kong Y., Zhang S., Wu R., Su X., Peng D., Zhao M., Su Y. New insights into different adipokines in linking the pathophysiology of obesity and psoriasis. Lipids Health Dis. 2019;18:171. doi: 10.1186/s12944-019-1115-3.
    1. Cerman A.A., Bozkurt S., Sav A., Tulunay A., Elbaşi M.O., Ergun T. Serum leptin levels, skin leptin and leptin receptor expression in psoriasis. Br. J. Dermatol. 2008;159:820–826. doi: 10.1111/j.1365-2133.2008.08742.x.
    1. Aly D.G., Abdallah I.Y., Hanafy N.S., Elsaie M.L., Hafiz N.A. Elevated serum leptin levels in nonobese patients with psoriasis. J. Drugs Dermatol. JDD. 2013;12:e25-9.
    1. Kyriakou A., Patsatsi A., Sotiriadis D., Goulis D.G. Serum Leptin, Resistin, and Adiponectin Concentrations in Psoriasis: A Meta-Analysis of Observational Studies. Dermatology. 2017;233:378–389. doi: 10.1159/000481882.
    1. Wang Y., Chen J., Zhao Y., Geng L., Song F., Chen H.D. Psoriasis is associated with increased levels of serum leptin. Br. J. Dermatol. 2008;158:1134–1135. doi: 10.1111/j.1365-2133.2008.08456.x.
    1. Baran A., Flisiak I., Jaroszewicz J., Świderska M. Serum adiponectin and leptin levels in psoriatic patients according to topical treatment. J. Dermatol. Treat. 2015;26:134–138. doi: 10.3109/09546634.2014.915917.
    1. Johnston A., Arnadottir S., Gudjonsson J.E., Aphale A., Sigmarsdottir A.A., Gunnarsson S.I., Steinsson J.T., Elder J.T., Valdimarsson H. Obesity in psoriasis: Leptin and resistin as mediators of cutaneous inflammation. Br. J. Dermatol. 2008;159:342–350. doi: 10.1111/j.1365-2133.2008.08655.x.
    1. Mitsuyama S., Abe F., Kimura M., Yoshida M., Higuchi T. Association between leptin gene expression in subcutaneous adipose tissue and circulating leptin levels in obese patients with psoriasis. Arch. Dermatol. Res. 2015;307:539–544. doi: 10.1007/s00403-015-1581-z.
    1. Takahashi H., Tsuji H., Honma M., Ishida-Yamamoto A., Iizuka H. Increased plasma resistin and decreased omentin levels in Japanese patients with psoriasis. Arch. Dermatol. Res. 2013;305:113–116. doi: 10.1007/s00403-012-1310-9.
    1. Huang K., Chen A., Zhang X., Song Z., Xu H., Cao J., Yin Y. Progranulin is preferentially expressed in patients with psoriasis vulgaris and protects mice from psoriasis-like skin inflammation. Immunology. 2015;145:279–287. doi: 10.1111/imm.12446.
    1. Rubina K.A., Sysoeva V.Y., Zagorujko E.I., Tsokolaeva Z.I., Kurdina M.I., Parfyonova Y.V., Tkachuk V.A. Increased expression of uPA, uPAR, and PAI-1 in psoriatic skin and in basal cell carcinomas. Arch. Dermatol. Res. 2017;309:433–442. doi: 10.1007/s00403-017-1738-z.
    1. Ismail S.A., Mohamed S.A. Serum levels of visfatin and omentin-1 in patients with psoriasis and their relation to disease severity. Br. J. Dermatol. 2012;167:436–439. doi: 10.1111/j.1365-2133.2012.10980.x.
    1. Sereflican B., Goksugur N., Bugdayci G., Polat M., Haydar Parlak A. Serum Visfatin, adiponectin, and tumor necrosis factor alpha (TNF-alpha) levels in patients with psoriasis and their correlation with disease severity. Acta Dermatovenerol. Croat. 2016;24:13–19.
    1. Albanesi C., Scarponi C., Pallotta S., Daniele R., Bosisio D., Madonna S., Fortugno P., Gonzalvo-Feo S., Franssen J.D., Parmentier M., et al. Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment. J. Exp. Med. 2009;206:249–258. doi: 10.1084/jem.20080129.
    1. Rollman O., Vahlquist A. Psoriasis and vitamin A. Plasma transport and skin content of retinol, dehydroretinol and carotenoids in adult patients versus healthy controls. Arch. Dermatol. Res. 1985;278:17–24. doi: 10.1007/BF00412490.
    1. Uysal S., Yılmaz F.M., Karatoprak K., Artüz F., Cumbul N.U. The levels of serum pentraxin3, CRP, fetuin-A, and insulin in patients with psoriasis. Eur. Rev. Med. Pharmacol. Sci. 2014;18:3453–3458.
    1. Gerdes S., Osadtschy S., Buhles N., Baurecht H., Mrowietz U. Cardiovascular biomarkers in patients with psoriasis. Exp. Dermatol. 2014;23:322–325. doi: 10.1111/exd.12381.
    1. Uyar B., Akyildiz M., Solak A., Genc B., Saklamaz A. Relationship Between Serum Fetuin-A Levels and Carotid Intima-media Thickness in Turkish Patients with Mild to Moderate Psoriasis. A Case-control Study. Acta Dermatovenerol. Croat. 2015;23:171–177.
    1. Li R.C., Krishnamoorthy P., DerOhannessian S., Doveikis J., Wilcox M., Thomas P., Rader D.J., Reilly M.P., Van Voorhees A., Gelfand J.M., et al. Psoriasis is associated with decreased plasma adiponectin levels independently of cardiometabolic risk factors. Clin. Exp. Dermatol. 2014;39:19–24. doi: 10.1111/ced.12250.
    1. Coimbra S., Oliveira H., Reis F., Belo L., Rocha S., Quintanilha A., Figueiredo A., Teixeira F., Castro E., Rocha-Pereira P., et al. Circulating adipokine levels in Portuguese patients with psoriasis vulgaris according to body mass index, severity and therapy. J. Eur. Acad. Dermatol. Venereol. 2010;24:1386–1394. doi: 10.1111/j.1468-3083.2010.03647.x.
    1. Shibata S., Saeki H., Tada Y., Karakawa M., Komine M., Tamaki K. Serum high molecular weight adiponectin levels are decreased in psoriasis patients. J. Dermatol. Sci. 2009;55:62–63. doi: 10.1016/j.jdermsci.2009.02.009.
    1. Gerdes S., Pinter A., Biermann M., Papavassilis C., Reinhardt M. Adiponectin levels in a large pooled plaque psoriasis study population. J. Dermatol. Treat. 2020;31:531–534. doi: 10.1080/09546634.2019.1621979.
    1. Turan H., Yaykasli K.O., Soguktas H., Yaykasli E., Aliagaoglu C., Erdem T., Karkucak M., Kaya E., Ucgun T., Bahadir A. Omentin serum levels and omentin gene Val109Asp polymorphism in patients with psoriasis. Int. J. Dermatol. 2014;53:601–605. doi: 10.1111/ijd.12306.
    1. Shibata S., Tada Y., Hau C.S., Mitsui A., Kamata M., Asano Y., Sugaya M., Kadono T., Masamoto Y., Kurokawa M., et al. Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from gammadelta-T cells. Nat. Commun. 2015;6:7687. doi: 10.1038/ncomms8687.
    1. Shibata S., Tada Y., Hau C., Tatsuta A., Yamamoto M., Kamata M., Karakawa M., Asano Y., Mitsui H., Sugaya M., et al. Adiponectin as an anti-inflammatory factor in the pathogenesis of psoriasis: Induction of elevated serum adiponectin levels following therapy. Br. J. Dermatol. 2011;164:667–670. doi: 10.1111/j.1365-2133.2010.10123.x.
    1. Ataseven A., Kesli R. Novel inflammatory markers in psoriasis vulgaris: Vaspin, vascular adhesion protein-1 (VAP-1), and YKL-40. G. Ital. Dermatol. Venereol. Organo Uff. Soc. Ital. Dermatol. Sifilogr. 2016;151:244–250.
    1. Rittié L., Tejasvi T., Harms P.W., Xing X., Nair R.P., Gudjonsson J.E., Swindell W.R., Elder J.T. Sebaceous Gland Atrophy in Psoriasis: An Explanation for Psoriatic Alopecia? J. Investig. Dermatol. 2016;136:1792–1800. doi: 10.1016/j.jid.2016.05.113.
    1. Karpouzis A., Tripsianis G., Gatzidou E. Assessment of Leptin Gene Polymorphism rs2060713 in Psoriasis Vulgaris. Int. Sch. Res. Not. 2014;2014:845272. doi: 10.1155/2014/845272.
    1. Abdel Hay R.M., Rashed L.A. Association between the leptin gene 2548G/A polymorphism, the plasma leptin and the metabolic syndrome with psoriasis. Exp. Dermatol. 2011;20:715–719. doi: 10.1111/j.1600-0625.2011.01299.x.
    1. Torres T., Bettencourt N., Ferreira J., Carvalho C., Mendonça D., Vasconcelos C., Selores M., Silva B. Lack of association between leptin, leptin receptor, adiponectin gene polymorphisms and epicardial adipose tissue, abdominal visceral fat volume and atherosclerotic burden in psoriasis patients. Arch. Physiol. Biochem. 2015;121:103–108. doi: 10.3109/13813455.2015.1024136.
    1. Werfel T., Allam J.P., Biedermann T., Eyerich K., Gilles S., Guttman-Yassky E., Hoetzenecker W., Knol E., Simon H.U., Wollenberg A., et al. Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J. Allergy Clin. Immunol. 2016;138:336–349. doi: 10.1016/j.jaci.2016.06.010.
    1. Kimata H. Elevated serum leptin in AEDS. Allergy. 2002;57:179. doi: 10.1034/j.1398-9995.2002.1n3549.x.
    1. Jaworek A.K., Szepietowski J.C. Adipokines as biomarkers of atopic dermatitis in adults. J. Clin. Med. 2020;9:2858. doi: 10.3390/jcm9092858.
    1. Nagel G., Koenig W., Rapp K., Wabitsch M., Zoellner I., Weiland S.K. Associations of adipokines with asthma, rhinoconjunctivitis, and eczema in German schoolchildren. Pediatr. Allergy Immunol. Off. Publ. Eur. Soc. Pediatr. Allergy Immunol. 2009;20:81–88. doi: 10.1111/j.1399-3038.2008.00740.x.
    1. Bostanci I., Atli O., Celebi N., Taşar A., Alpkarakoç E., Dallar Y. Serum leptin level in children with atopic dermatitis-treated topical steroids. Pediatr. Allergy Immunol. Off. Publ. Eur. Soc. Pediatr. Allergy Immunol. 2004;15:267–269. doi: 10.1111/j.1399-3038.2004.00145.x.
    1. Balato N., Nino M., Patruno C., Matarese G., Ayala F. “Eczemas” and leptin. Dermatitis. 2011;22:320–323. doi: 10.2310/6620.2011.11038.
    1. Machura E., Szczepanska M., Ziora K., Ziora D., Swietochowska E., Barc-Czarnecka M., Kasperska-Zajac A. Evaluation of adipokines: Apelin, visfatin, and resistin in children with atopic dermatitis. Mediat. Inflamm. 2013;2013:760691. doi: 10.1155/2013/760691.
    1. Farag A.G.A., Hammam M.A., Khaled H.N., Soliman S., Tayel N.R., El-Shamendy A.A., Shehata W.A. Resistin adipokin in atopic dermatitis patients: A clinical, biochemical, and genetic study. J. Cosmet. Dermatol. 2020 doi: 10.1111/jocd.13338.
    1. Aizawa N., Ishiuji Y., Tominaga M., Sakata S., Takahashi N., Yanaba K. Relationship between the Degrees of Itch and Serum Lipocalin-2 Levels in Patients with Psoriasis. J. Immunol. Res. 2019;2019:8171373. doi: 10.1155/2019/8171373.
    1. Kamata M., Tada Y., Tatsuta A., Kawashima T., Shibata S., Mitsui H., Asano Y., Sugaya M., Kadono T., Kanda N., et al. Serum lipocalin-2 levels are increased in patients with psoriasis. Clin. Exp. Dermatol. 2012;37:296–299. doi: 10.1111/j.1365-2230.2011.04265.x.
    1. Noh J.Y., Shin J.U., Kim J.H., Kim S.H., Kim B.M., Kim Y.H., Park S., Kim T.G., Shin K.O., Park K., et al. ZAG Regulates the Skin Barrier and Immunity in Atopic Dermatitis. J. Investig. Dermatol. 2019;139:1648–1657.e1647. doi: 10.1016/j.jid.2019.01.023.
    1. Han B., Wu W.H., Bae J.M., Son S.J., Lee J.H., Han T.Y. Serum leptin and adiponectin levels in atopic dermatitis (AD) and their relation to disease severity. J. Am. Acad. Dermatol. 2016;75:629–631. doi: 10.1016/j.jaad.2016.04.036.
    1. Banihani S.A., Elmadhoun R.A., Khabour O.F., Alzoubi K.H. The rs2167270 polymorphism of leptin gene is associated with atopic dermatitis. Derm. Endocrinol. 2018;10:e1454191. doi: 10.1080/19381980.2018.1454191.
    1. Banihani S.A., Abu-Alia K.F., Khabour O.F. Association between resistin gene polymorphisms and atopic dermatitis. Biomolecules. 2018;8:17. doi: 10.3390/biom8020017.
    1. Zouboulis C.C., Jourdan E., Picardo M. Acne is an inflammatory disease and alterations of sebum composition initiate acne lesions. J. Eur. Acad. Dermatol. Venereol. 2014;28:527–532. doi: 10.1111/jdv.12298.
    1. Pérez-Pérez A., Vilariño-García T., Fernández-Riejos P., Martín-González J., Segura-Egea J.J., Sánchez-Margalet V. Role of leptin as a link between metabolism and the immune system. Cytokine Growth Factor Rev. 2017;35:71–84. doi: 10.1016/j.cytogfr.2017.03.001.
    1. Ingham E., Eady E.A., Goodwin C.E., Cove J.H., Cunliffe W.J. Pro-inflammatory levels of interleukin-1 alpha-like bioactivity are present in the majority of open comedones in acne vulgaris. J. Investig. Dermatol. 1992;98:895–901. doi: 10.1111/1523-1747.ep12460324.
    1. Reis B.S., Lee K., Fanok M.H., Mascaraque C., Amoury M., Cohn L.B., Rogoz A., Dallner O.S., Moraes-Vieira P.M., Domingos A.I., et al. Leptin receptor signaling in T cells is required for Th17 differentiation. J. Immunol. 2015;194:5253–5260. doi: 10.4049/jimmunol.1402996.
    1. Kelhälä H.L., Palatsi R., Fyhrquist N., Lehtimäki S., Väyrynen J.P., Kallioinen M., Kubin M.E., Greco D., Tasanen K., Alenius H., et al. IL-17/Th17 pathway is activated in acne lesions. PLoS ONE. 2014;9:e105238. doi: 10.1371/journal.pone.0105238.
    1. Danby F.W. Ductal hypoxia in acne: Is it the missing link between comedogenesis and inflammation? J. Am. Acad. Dermatol. 2014;70:948–949. doi: 10.1016/j.jaad.2013.11.029.
    1. Dodd K.M., Yang J., Shen M.H., Sampson J.R., Tee A.R. mTORC1 drives HIF-1alpha and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3. Oncogene. 2015;34:2239–2250. doi: 10.1038/onc.2014.164.
    1. Kaymak Y., Adisen E., Ilter N., Bideci A., Gurler D., Celik B. Dietary glycemic index and glucose, insulin, insulin-like growth factor-I, insulin-like growth factor binding protein 3, and leptin levels in patients with acne. J. Am. Acad. Dermatol. 2007;57:819–823. doi: 10.1016/j.jaad.2007.06.028.
    1. Chang H.C., Lin M.H., Huang Y.C. Association between circulating adipokines and acne vulgaris: A systematic review and meta-analysis. Australas J. Dermatol. 2019;60:e361–e364. doi: 10.1111/ajd.13035.
    1. Çerman A.A., Aktaş E., Altunay İ.K., Arıcı J.E., Tulunay A., Ozturk F.Y. Dietary glycemic factors, insulin resistance, and adiponectin levels in acne vulgaris. J. Am. Acad. Dermatol. 2016;75:155–162. doi: 10.1016/j.jaad.2016.02.1220.
    1. Aydin K., Çetinözman F., Elcin G., Aksoy D.Y., Ucar F., Yildiz B.O. Suppressed Adiponectin Levels and Increased Adiponectin Response to Oral Glucose Load in Lean Women with Severe Acne Normalizes after Isotretinoin Treatment. Dermatology. 2017;233:314–319. doi: 10.1159/000484168.
    1. Karadag A.S., Ertugrul D.T., Takci Z., Bilgili S.G., Namuslu M., Ata N., Sekeroglu R. The effect of isotretinoin on retinol-binding protein 4, leptin, adiponectin and insulin resistance in acne vulgaris patients. Dermatology. 2015;230:70–74. doi: 10.1159/000367687.
    1. Hussain S., Faraz A., Iqbal T. The RETN gene rs1862513 polymorphism as a novel predisposing marker for familial Acne vulgaris in a Pakistani population. Iran. J. Basic Med. Sci. 2015;18:526–528.
    1. Younis S., Blumenberg M., Javed Q. Resistin gene polymorphisms are associated with acne and serum lipid levels, providing a potential nexus between lipid metabolism and inflammation. Arch. Dermatol. Res. 2016;308:229–237. doi: 10.1007/s00403-016-1626-y.
    1. Soguktas H., Yaykasli K.O., Turan H., Kaya E., Yaykasli E. Omentin Val/Val genotype increases predisposition to acne vulgaris without changing omentin serum level. Cell. Mol. Biol. 2018;64:81–86. doi: 10.14715/cmb/2018.64.12.16.
    1. Ahn C.S., Huang W.W. Rosacea Pathogenesis. Dermatol. Clin. 2018;36:81–86. doi: 10.1016/j.det.2017.11.001.
    1. Gerber P.A., Buhren B.A., Steinhoff M., Homey B. Rosacea: The cytokine and chemokine network. J. Investig. Dermatology. Symp. Proc. 2011;15:40–47. doi: 10.1038/jidsymp.2011.9.
    1. Rainer B.M., Kang S., Chien A.L. Rosacea: Epidemiology, pathogenesis, and treatment. Derm. Endocrinol. 2017;9:e1361574. doi: 10.1080/19381980.2017.1361574.
    1. Amir Ali A., Vender R., Vender R. The Role of IL-17 in Papulopustular Rosacea and Future Directions. J. Cutan. Med. Surg. 2019;23:635–641. doi: 10.1177/1203475419867611.
    1. Li T., Zeng Q., Chen X., Wang G., Zhang H., Yu A., Wang H., Hu Y. The therapeutic effect of artesunate on rosacea through the inhibition of the JAK/STAT signaling pathway. Mol. Med. Rep. 2018;17:8385–8390. doi: 10.3892/mmr.2018.8887.
    1. Thibaut de Ménonville S., Rosignoli C., Soares E., Roquet M., Bertino B., Chappuis J.P., Defoin-Platel/Chaussade C., Piwnica D. Topical Treatment of Rosacea with Ivermectin Inhibits Gene Expression of Cathelicidin Innate Immune Mediators, LL-37 and KLK5, in Reconstructed and Ex Vivo Skin Models. Dermatol. Ther. 2017;7:213–225. doi: 10.1007/s13555-017-0176-3.
    1. Yuan X., Li J., Li Y., Deng Z., Zhou L., Long J., Tang Y., Zuo Z., Zhang Y., Xie H. Artemisinin, a potential option to inhibit inflammation and angiogenesis in rosacea. Biomed. Pharmacother. Biomed. Pharmacother. 2019;117:109181. doi: 10.1016/j.biopha.2019.109181.
    1. Topcu-Yilmaz P., Atakan N., Bozkurt B., Irkec M., Aban D., Mesci L., Tezcan I. Determination of tear and serum inflammatory cytokines in patients with rosacea using multiplex bead technology. Ocul. Immunol. Inflamm. 2013;21:351–359. doi: 10.3109/09273948.2013.795229.
    1. Fischer J., Meyer-Hoffert U. Regulation of kallikrein-related peptidases in the skin—From physiology to diseases to therapeutic options. Thromb. Haemost. 2013;110:442–449. doi: 10.1160/TH12-11-0836.
    1. Di Paolo C.T., Diamandis E.P., Prassas I. The role of kallikreins in inflammatory skin disorders and their potential as therapeutic targets. Crit. Rev. Clin. Lab. Sci. 2020:1–16. doi: 10.1080/10408363.2020.1775171.
    1. Meyer-Hoffert U. Reddish, scaly, and itchy: How proteases and their inhibitors contribute to inflammatory skin diseases. Arch. Immunol. Ther. Exp. 2009;57:345–354. doi: 10.1007/s00005-009-0045-6.
    1. Medgyesi B., Dajnoki Z., Béke G., Gáspár K., Szabó I.L., Janka E.A., Póliska S., Hendrik Z., Méhes G., Törőcsik D., et al. Rosacea Is Characterized by a Profoundly Diminished Skin Barrier. J. Investig. Dermatol. 2020;140:1938–1950.e1935. doi: 10.1016/j.jid.2020.02.025.
    1. Tímár J., Vizkeleti L., Doma V., Barbai T., Rásó E. Genetic progression of malignant melanoma. Cancer Metastasis Rev. 2016;35:93–107. doi: 10.1007/s10555-016-9613-5.
    1. Sergentanis T.N., Antoniadis A.G., Gogas H.J., Antonopoulos C.N., Adami H.O., Ekbom A., Petridou E.T. Obesity and risk of malignant melanoma: A meta-analysis of cohort and case-control studies. Eur. J. Cancer. 2013;49:642–657. doi: 10.1016/j.ejca.2012.08.028.
    1. Renehan A.G., Tyson M., Egger M., Heller R.F., Zwahlen M. Body-mass index and incidence of cancer: A systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371:569–578. doi: 10.1016/S0140-6736(08)60269-X.
    1. Præstegaard C., Kjær S.K., Christensen J., Tjønneland A., Halkjær J., Jensen A. Obesity and risks for malignant melanoma and non-melanoma skin cancer: Results from a large Danish prospective cohort study. J. Investig. Dermatol. 2015;135:901–904. doi: 10.1038/jid.2014.438.
    1. Malvi P., Chaube B., Singh S.V., Mohammad N., Vijayakumar M.V., Singh S., Chouhan S., Bhat M.K. Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state. Cancer Metab. 2018;6:2. doi: 10.1186/s40170-018-0176-5.
    1. Brandon E.L., Gu J.W., Cantwell L., He Z., Wallace G., Hall J.E. Obesity promotes melanoma tumor growth: Role of leptin. Cancer Biol. Ther. 2009;8:1871–1879. doi: 10.4161/cbt.8.19.9650.
    1. Malvi P., Chaube B., Pandey V., Vijayakumar M.V., Boreddy P.R., Mohammad N., Singh S.V., Bhat M.K. Obesity induced rapid melanoma progression is reversed by orlistat treatment and dietary intervention: Role of adipokines. Mol. Oncol. 2015;9:689–703. doi: 10.1016/j.molonc.2014.11.006.
    1. Ellerhorst J.A., Diwan A.H., Dang S.M., Uffort D.G., Johnson M.K., Cooke C.P., Grimm E.A. Promotion of melanoma growth by the metabolic hormone leptin. Oncol. Rep. 2010;23:901–907. doi: 10.3892/or_00000713.
    1. Chi M., Chen J., Ye Y., Tseng H.Y., Lai F., Tay K.H., Jin L., Guo S.T., Jiang C.C., Zhang X.D. Adipocytes contribute to resistance of human melanoma cells to chemotherapy and targeted therapy. Curr. Med. Chem. 2014;21:1255–1267. doi: 10.2174/0929867321666131129114742.
    1. Gogas H., Trakatelli M., Dessypris N., Terzidis A., Katsambas A., Chrousos G.P., Petridou E.T. Melanoma risk in association with serum leptin levels and lifestyle parameters: A case-control study. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2008;19:384–389. doi: 10.1093/annonc/mdm464.
    1. Mizutani H., Fukushima S., Masuguchi S., Yamashita J., Miyashita A., Nakahara S., Aoi J., Inoue Y., Jinnin M., Ihn H. Serum levels of leptin receptor in patients with malignant melanoma as a new tumor marker. Exp. Dermatol. 2013;22:748–749. doi: 10.1111/exd.12238.
    1. Amjadi F., Mehdipoor R., Zarkesh-Esfahani H., Javanmard S.H. Leptin serves as angiogenic/mitogenic factor in melanoma tumor growth. Adv. Biomed. Res. 2016;5:127. doi: 10.4103/2277-9175.187005.
    1. Berta J., Hoda M.A., Laszlo V., Rozsas A., Garay T., Torok S., Grusch M., Berger W., Paku S., Renyi-Vamos F., et al. Apelin promotes lymphangiogenesis and lymph node metastasis. Oncotarget. 2014;5:4426–4437. doi: 10.18632/oncotarget.2032.
    1. Bułdak R.J., Bułdak Ł., Polaniak R., Kukla M., Birkner E., Kubina R., Kabała-Dzik A., Duława-Bułdak A., Żwirska-Korczala K. Visfatin affects redox adaptative responses and proliferation in Me45 human malignant melanoma cells: An in vitro study. Oncol. Rep. 2013;29:771–778. doi: 10.3892/or.2012.2175.
    1. Grolla A.A., Torretta S., Gnemmi I., Amoruso A., Orsomando G., Gatti M., Caldarelli A., Lim D., Penengo L., Brunelleschi S., et al. Nicotinamide phosphoribosyltransferase (NAMPT/PBEF/visfatin) is a tumoural cytokine released from melanoma. Pigment. Cell Melanoma Res. 2015;28:718–729. doi: 10.1111/pcmr.12420.
    1. Audrito V., Managò A., Zamporlini F., Rulli E., Gaudino F., Madonna G., D’Atri S., Antonini Cappellini G.C., Ascierto P.A., Massi D., et al. Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is a novel marker for patients with BRAF-mutated metastatic melanoma. Oncotarget. 2018;9:18997–19005. doi: 10.18632/oncotarget.24871.
    1. Pachynski R.K., Zabel B.A., Kohrt H.E., Tejeda N.M., Monnier J., Swanson C.D., Holzer A.K., Gentles A.J., Sperinde G.V., Edalati A., et al. The chemoattractant chemerin suppresses melanoma by recruiting natural killer cell antitumor defenses. J. Exp. Med. 2012;209:1427–1435. doi: 10.1084/jem.20112124.
    1. Song Y., Yin W., Dan Y., Sheng J., Zeng Y., He R. Chemerin partly mediates tumor-inhibitory effect of all-trans retinoic acid via CMKLR1-dependent natural killer cell recruitment. Immunology. 2019;157:248–256. doi: 10.1111/imm.13065.
    1. Klein R.M., Bernstein D., Higgins S.P., Higgins C.E., Higgins P.J. SERPINE1 expression discriminates site-specific metastasis in human melanoma. Exp. Dermatol. 2012;21:551–554. doi: 10.1111/j.1600-0625.2012.01523.x.
    1. Mantzoros C.S., Trakatelli M., Gogas H., Dessypris N., Stratigos A., Chrousos G.P., Petridou E.T. Circulating adiponectin levels in relation to melanoma: A case-control study. Eur. J. Cancer. 2007;43:1430–1436. doi: 10.1016/j.ejca.2007.03.026.
    1. Blüher M. Adipokines—Removing road blocks to obesity and diabetes therapy. Mol. Metab. 2014;3:230–240. doi: 10.1016/j.molmet.2014.01.005.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere