JCDSA  Vol.3 No.1 , March 2013
Suppression of Sebum Production and Accumulation by β-Cryptoxanthin Due to the Inhibition of the Expression of Diacylglycerol Acyltransferase-1 and Perilipin in Hamster Sebocytes
Abstract

Background: Acne vulgaris is characterized by the enhancement of sebaceous lipogenesis and sebum secretion, and apart from retinoids and some natural products there are few effective antiacne agents that directly suppress sebum production and accumulation in sebaceous glands. Objective: We examined the effects of β-cryptoxanthin (β-CRX), which is a carotenoid pigment most abundant in Citrus unshiu Marcovich (Satsuma mandarin orange) and plays a role as a vitamin A precursor on sebum production and accumulation in hamster sebaceous gland cells (sebocytes). Materials and methods: The regulation of sebum production was examined by the measurement of triacylglycerols (TGs), the major sebum component, and oil red O staining in insulindifferentiated hamster sebocytes. The expression of diacylglycerol acyltransferase-1 (DGAT-1), a rate-limiting enzyme of TG biosynthesis, and perilipin 1 (PLIN1), a lipid storage droplet protein, was analyzed using real-time PCR and Western blotting. Results: Hamster sebocytes constitutively produced TGs during cultivation and the production of TGs was enhanced by insulin treatment. Both constitutive and insulin-enhanced TG productions were dose- and time-dependently inhibited by β-CRX as well as 13-cis retinoic acid. In addition, the gene expression of DGAT-1 was suppressed by β-CRX in the sebocytes. Furthermore, the insulin-en- hanced sebum accumulation as lipid droplets was reduced in the β-CRX-treated cells. Moreover, β-CRX was found to suppress the gene expression and production of PLIN1 in insulin-differentiated hamster sebocytes. Conclusions: These results provide novel evidence that β-CRX is an effective candidate for acne therapy by its ability to exert dual inhibitory actions against DGAT-1-dependent TG production and PLIN1-mediated lipiddroplet formation in hamster sebocytes.


Cite this paper
T. Sato, Y. Shirakura, K. Mukai and A. Ito, "Suppression of Sebum Production and Accumulation by β-Cryptoxanthin Due to the Inhibition of the Expression of Diacylglycerol Acyltransferase-1 and Perilipin in Hamster Sebocytes," Journal of Cosmetics, Dermatological Sciences and Applications, Vol. 3 No. 1, 2013, pp. 99-106. doi: 10.4236/jcdsa.2013.31014.
References

[1]   H. Pawin, C. Beylot, M. Chivot, M. Faure, F. Poli, J. Revuz and B. Dréno, “Physiopathology of Acne Vulgaris: Recent Data, New Understanding of the Treatments,” European Journal of Dermatology, Vol. 14, No. 1, 2004, pp. 4-12.

[2]   C. C. Zouboulis, A. Eady, M. Philpott, L. A. Goldsmith, C. Orfanos, W. C. Cunliffe and R. Rosenfield, “What Is the Pathogenesis of Acne?” Experimental Dermatology, Vo. 14, No. 2, 2005, pp. 143-152. Hdoi:10.1111/j.0906-6705.2005.0285a.x

[3]   H. C. Williams, R. P. Dellavalle and S. Garner, “Acne Vulgaris,” Lancet, Vol. 379, No. 9813, 2012, pp. 361-372. Hdoi:10.1016/S0140-6736(11)60321-8

[4]   I. Kurokawa, F. W. Danby, Q. Ju, X. Wang, L. F. Xiang, L. Xia, W. Chen, I. Nagy, M. Picardo, D. H. Suh, R. Ganceviciene, S. Schagen, F. Tsatsou and C. C. Zouboulis, “New Developments in Our Understanding of Acne Pathogenesis and Treatment,” Experimental Dermatology, Vol. 18, No. 10, 2009, pp. 821-832. Hdoi:10.1111/j.1600-0625.2009.00890.x

[5]   R. L. Rosenfield, A. Kentsis, D. Deplewski and N. Ciletti, “Rat Preputial Sebocyte Differentiation Involves Peroxisome Proliferator-Activated Receptors,” Journal of Investigative Dermatology, Vol. 112, No. 2, 1999, pp. 226-232. Hdoi:10.1046/j.1523-1747.1999.00487.x

[6]   C. Iwata, N. Akimoto, T. Sato, Y. Morokuma and A. Ito, “Augmentation of Lipogenesis by 15-Deoxy-δ12,14-Prostaglandin J2 in Hamster Sebaceous Glands: Identification of Cytochrome P-450-Mediated 15-deoxy-δ12,14-Prostaglandin J2 Production,” Journal of Investigative Dermatology, Vol. 125, No. 5, 2005, pp. 865-872.

[7]   T. Alestas, R. Ganceviciene, S. Fimmel, K. Müller-Decker and C. C. Zouboulis, “Enzymes Involved in the Biosynthesis of Leukotriene B4 and Prostaglandin E2 Are Active in Sebaceous Glands,” Journal of Molecular Medicine, Vol. 84, No. 1, 2006, pp. 75-87. Hdoi:10.1007/s00109-005-0715-8

[8]   T. M. Smith, Z. Cong, K. L. Gilliland, G. A. Clawson and D. M. Thiboutot, “Insulin-Like Growth Factor-1 Induces Lipid Production in Human SEB-1 Sebocytes via Sterol Response Element-Binding Protein-1,” Journal of Investigative Dermatology, Vol. 126, No. 6, 2006, pp. 1226-1232. Hdoi:10.1038/sj.jid.5700278

[9]   N. R. Trivedi, K. L. Gilliland, W. Zhao, W. Liu and D. M. Thiboutot, “Gene Array Expression Profiling in Acne Lesions Reveals Marked Upregulation of Genes Involved in Inflammation and Matrix Remodeling,” Journal of Investigative Dermatology, Vol. 126, No. 5, 2006, pp. 1071-1079. Hdoi:10.1038/sj.jid.5700213

[10]   A. Turkish and S. L. Sturley, “Regulation of Triglyceride Metabolism. I. Eukaryotic Neutral Lipid Synthesis: ‘Many Ways to Skin ACAT or a DGAT’,” American Journal of Physiology. Gastrointestinal and Liver Physiology, Vol. 292, No. 4, 2007, pp. G953-957.

[11]   L. Ge, J. S. Gordon, C. Hsuan, K. Stenn and S. M. Prouty, “Identification of the Δ-6 Desaturase of Human Sebaceous Glands: Expression and Enzyme Activity,” Journal of Investigative Dermatology, Vol. 120, No. 5, 2003, pp. 707-714. Hdoi:10.1046/j.1523-1747.2003.12123.x

[12]   N. Akimoto, T. Sato, C. Iwata, M. Koshizuka, F. Shibata, A. Nagai, M. Sumida and A. Ito, “Expression of Perilipin A on the Surface of Lipid Droplets Increases along with the Differentiation of Hamster Sebocytes in Vivo and in Vitro,” Journal of Investigative Dermatology, Vol. 124, No. 6, 2005, pp. 1127-1133. Hdoi:10.1111/j.0022-202X.2005.23718.x

[13]   A. Krautheim and H. P. Gollnick, “Acne: Topical Treatment,” Clinics in Dermatology, Vol. 22, No. 5, 2004, pp. 398-407. Hdoi:10.1016/j.clindermatol.2004.03.009

[14]   J. B. Bikowski, “Mechanisms of the Comedolytic and Anti-Inflammatory Properties of Topical Retinoids,” Journal of Drugs in Dermatology, Vol. 4, No. 1, 2005, pp. 41-47.

[15]   I. Tenaud, A. Khammari and B. Dreno, “In Vitro Modulation of TLR-2, CD1d and IL-10 by Adapalene on Normal Human Skin and Acne Inflammatory Lesions,” Experimental Dermatology, Vol. 16, No. 6, 2007, pp. 500-506. Hdoi:10.1111/j.1600-0625.2007.00552.x

[16]   C. C. Zouboulis, B. Korge, H. Akamatsu, L. Q. Xia, S. Schiller, H. Gollnick and C. E. Orfanos, “Effects of 13-cisRetinoic Acid, All-trans-Retinoic Acid, and Acitretin on the Proliferation, Lipid Synthesis and Keratin Expression of Cultured Human Sebocytes in Vitro,” Journal of Investigative Dermatology, Vol. 96, No. 5, 1991, pp. 792-797. Hdoi:10.1111/1523-1747.ep12471782

[17]   M. J. Kim, N. Ciletti, S. Michel, U. Reichert and R. L. Rosenfield, “The Role of Specific Retinoid Receptors in Sebocyte Growth and Differentiation in Culture,” Journal of Investigative Dermatology, Vol. 114, No. 2, 2000, pp. 349-353. Hdoi:10.1046/j.1523-1747.2000.00868.x

[18]   T. Sato, A. Takahashi, M. Kojima, N. Akimoto, M. Yano and A. Ito, “A Citrus Polymethoxy Flavonoid, Nobiletin Inhibits Sebum Production and Sebocyte Proliferation, and Augments Sebum Excretion in Hamsters,” Journal of Investigative Dermatology, Vol. 127, No. 12, 2007, pp. 2740-2748.

[19]   A. M. Nelson, K. L. Gilliland, Z. Cong and D. M. Thiboutot, “13-cis Retinoic Acid Induces Apoptosis and Cell Cycle Arrest in Human SEB-1 Sebocytes,” Journal of Investigative Dermatology, Vol. 126, No. 10, 2006, pp. 2178-2189. Hdoi:10.1038/sj.jid.5700289

[20]   A. J. Young and G. M. Lowe, “Antioxidant and Prooxidant Properties of Carotenoids,” Archives of Biochemistry and Biophysics, Vol. 385, No. 1, 2001, pp. 20-27. Hdoi:10.1006/abbi.2000.2149

[21]   A. Matsumoto, H. Mizukami, S. Mizuno, K. Umegaki, J. Nishikawa, K. Shudo, H. Kagechika and M. Inoue, “βCryptoxanthin, a Novel Natural RAR Ligand, Induces ATP-Binding Cassette Transporters in Macrophages,” Biochemical Pharmacology, Vol. 74, No. 2, 2007, pp. 256-264. Hdoi:10.1016/j.bcp.2007.04.014

[22]   G. Maiani, M. J. Castón, G. Catasta, E. Toti, I. G. Cambrodón, A. Bysted, F. Granado-Lorencio, B. OlmedillaAlonso, P. Knuthsen, M. Valoti, V. B?hm, E. Mayer-Miebach, D. Behsnilian and U. Schlemmer, “Carotenoids: Actual Knowledge on Food Sources, Intakes, Stability and Bioavailability and Their Protective Role in Humans,” Molecular Nutrition and Food Research, Vol. 53 Suppl 2, 2009, pp. S194-218. Hdoi:10.1002/mnfr.200800053

[23]   K. Takayanagi, S. Morimoto, Y. Shirakura, K. Mukai, T. Sugiyama, Y. Tokuji and M. Ohnishi, “Mechanism of Visceral Fat Reduction in Tsumura Suzuki Obese, Diabetes (TSOD) Mice Orally Administered β-Cryptoxanthin from Satsuma Mandarin Oranges (Citrus Unshiu Marc),” Journal of Agricultural and Food Chemistry, Vol. 59, No. 23, 2011, pp. 12342-12351. Hdoi:10.1021/jf202821u

[24]   M. Sugiura, H. Matsumoto, M. Kato, Y. Ikoma, M. Yano and A. Nagao, “Multiple Linear Regression Analysis of the Seasonal Changes in the Serum Concentration of βCryptoxanthin,” Journal of Nutritional Science and Vitaminology, Vol. 50, No. 3, 2004, pp. 196-202. Hdoi:10.3177/jnsv.50.196

[25]   S. Mannisto, S. A. Smith-Warner, D. Spiegelman, D. Albanes, K. Anderson, P. A. van den Brandt, J. R. Cerhan, G. Colditz, D. Feskanich, J. L. Freudenheim, E. Giovannucci, R. A. Goldbohm, S. Graham, A. B. Miller, T. E. Rohan, J. Virtamo, W. C. Willett and D. J. Hunter, “Dietary Carotenoids and Risk of Lung Cancer in a Pooled Analysis of Seven Cohort Studies,” Cancer Epidemiology, Biomarkers and Prevention, Vol. 13, No. 1, 2004, pp. 40-48. Hdoi:10.1158/1055-9965.EPI-038-3?

[26]   J. M. Yuan, D. O. Stram, K. Arakawa, H. P. Lee and M. C. Yu, “Dietary Cryptoxanthin and Reduced Risk of Lung Cancer: The Singapore Chinese Health Study,” Cancer Epidemiology, Biomarkers and Prevention, Vol. 12, No. 9, 2003, pp. 890-898.

[27]   D. J. Pattison, D. P. Symmons, M. Lunt, A. Welch, S. A. Bingham, N. E. Day and A. J. Silman, “Dietary β-Cryptoxanthin and Inflammatory Polyarthritis: Results from a Population-Based Prospective Study,” The American Journal of Clinical Nutrition, Vol. 82, No. 2, 2005, pp. 451-455.

[28]   Z. El-Akawi, N. Abdel-Latif and K. Abdul-Razzak, “Does the Plasma Level of Vitamins A and E Affect Acne Condition,” Clinical and Experimental Dermatology, Vol. 31, No. 3, 2006, pp. 430-434. Hdoi:10.1111/j.1365-2230.2006.02106.x

[29]   T. M. Redmond, S. Gentleman, T. Duncan, S. Yu, B. Wiggert, E. Gantt and F. X. Cunningham Jr., “Identification, Expression, and Substrate Specificity of a Mammalian β-Carotene 15,15'-Dioxygenase,” The Journal of Biological Chemistry, Vol. 276, No. 9, pp. 6560-6565. Hdoi:10.1074/jbc.M009030200

[30]   M. Sugiura, M. Kato, H. Matsumoto, A. Nagao and M. Yano, “Serum Concentration of β-Cryptoxanthin in Japan Reflects the Frequency of Satsuma Mandarin (Citrus unshiu Marc.) Consumption,” Journal of Health Sciences, Vol. 48, No. 4, 2002, pp. 350-353. Hdoi:10.1248/jhs.48.350

[31]   Y. Shirakura, K. Takayanagi, K. Mukai, H. Tanabe and M. Inoue, “β-Cryptoxanthin Suppresses the Adipogenesis of 3T3-L1 Cells via RAR Activation,” Journal of Nutritional Science and Vitaminology, Vol. 57, No. 6, 2011, pp. 426-431. Hdoi:10.3177/jnsv.57.426

[32]   T. Sato, N. Imai, N. Akimoto, T. Sakiguchi, K. Kitamura and A. Ito, “Epidermal Growth Factor and 1α,25-Dihydroxyvitamin D3 Suppress Lipogenesis in Hamster Sebaceous Gland Cells in Vitro,” Journal of Investigative Dermatology, Vol. 117, No. 4, 2001, pp. 965-970. Hdoi:10.1046/j.0022-202x.2001.01516.x

[33]   T. Sato, T. Shirane, N. Noguchi, M. Sasatsu and A. Ito, “Novel Anti-Acne Actions of Nadifloxacin and Clindamycin That Inhibit the Production of Sebum, Prostaglandin E2 and Promatrix Metalloproteinase-2 in Hamster Sebocytes,” Journal of Dermatology, Vol. 39, No. 9, 2012, pp. 774-780. Hdoi:10.1111/j.1346-8138.2012.01525.x

[34]   K. Iinuma, T. Sato, N. Akimoto, N. Noguchi, M. Sasatsu, S. Nishijima, I. Kurokawa and A. Ito, “Involvement of Propionibacterium acnes in the Augmentation of Lipogenesis in Hamster Sebaceous Glands in Vivo and in Vitro,” Journal of Investigative Dermatology, Vol. 129, No. 9, 2009, pp. 2113-2119. Hdoi:10.1038/jid.2009.46

[35]   A. R. Kimmel, D. L. Brasaemle, M. McAndrews-Hill, C. Sztalryd and C. Londos, “Adoption of PERILIPIN as a Unifying Nomenclature for the Mammalian PAT-Family of Intracellular Lipid Storage Droplet Proteins,” Journal of Lipid Research, Vol. 51, No. 3, 2010, pp. 468-471. Hdoi:10.1194/jlr.R000034

[36]   C. A. Harris, J. T. Haas, R. S. Streeper, S. J. Stone, M. Kumari, K. Yang, X. Han, N. Brownell, R. W. Gross, R. Zechner and R. V. Farese Jr., “DGAT Enzymes Are Required for Triacylglycerol Synthesis and Lipid Droplets in Adipocytes,” Journal of Lipid Research, Vol. 52, No. 4, 2011, pp. 657-667. Hdoi:10.1194/jlr.M013003

[37]   D. L. Brasaemle, B. Rubin, I. A. Harten, J. Gruia-Gray, A. R. Kimmel and C. Londos, “Perilipin A Increases Triacylglycerol Storage by Decreasing the Rate of Triacylglycerol Hydrolysis,” The Journal of Biological Chemistery, Vol. 275, No. 49, 2000, pp. 38486-38493. Hdoi:10.1074/jbc.M007322200

[38]   H. Wang, L. Hu, K. Dalen, H. Dorward, A. Marcinkiewicz, D. Russell, D. Gong, C. Londos, T. Yamaguchi, C. Holm, M. A. Rizzo, D. Brasaemle and C. Sztalryd, “Activation of Hormone-Sensitive Lipase Requires Two Steps, Protein Phosphorylation and Binding to the PAT-1 Domain of Lipid Droplet Coat Proteins,” The Journal of Biological Chemistery, Vol. 284, No. 46, 2009, pp. 32116-32125. Hdoi:10.1074/jbc.M109.006726

[39]   M. Kato, Y. Ikoma, H. Matsumoto, M. Sugiura, H. Hyodo and M. Yano, “Accumulation of Carotenoids and Expression of Carotenoid Biosynthetic Genes during Maturation in Citrus Fruit,” Plant Physiology, Vol. 134, No. 2, 2004, pp. 824-837. Hdoi:10.1104/pp.103.031104

[40]   H. A. Al-Wadei, T. Takahashi and H. M. Schuller, “Growth Stimulation of Human Pulmonary Adenocarcinoma Cells and Small Airway Epithelial Cells by β-Carotene via Activation of cAMP, PKA, CREB and ERK1/2,” International Journal of Cancer, Vol. 118, No. 6, 2006, pp. 1370-1380. Hdoi:10.1002/ijc.21537

[41]   H. A. Al-Wadei, M. Majidi, M. S. Tsao and H. M. Schuller, “Low Concentrations of β-Carotene Stimulate the Proliferation of Human Pancreatic Duct Epithelial Cells in a PKA-Dependent Manner,” Cancer Genomics and Proteomics, Vol. 4, No. 1, 2007, pp. 35-42.

[42]   W. J. Cunliffe, D. B. Holland, S. M. Clark and G. I. Stables, “Comedogenesis: Some New Aetiological, Clinical and Therapeutic Strategies,” The British Journal of Dermatology, Vol. 142, No. 6, 2000, pp. 1084-1091. Hdoi:10.1046/j.1365-2133.2000.03531.x

[43]   B. C. Melnik and G. Schmitz, “Role of Insulin, Insulin-Like Growth Factor-1, Hyperglycaemic Food and Milk Consumption in the Pathogenesis of Acne Vulgaris,” Experimental Dermatology, Vol. 18, No. 10, 2009, pp. 833-841. Hdoi:10.1111/j.1600-0625.2009.00924.x

[44]   C. C. Zouboulis, “Sebaceous Gland Receptors,” DermatoEndocrinology, Vol. 1, No. 2, 2009, pp. 77-80.

[45]   N. N. Elmongy and O. Shaker, “Expression of Peroxisome Proliferator Activator Receptor β/δ (PPAR β/δ) in Acne Vulgaris,” European Journal of Dermatology, Vol. 22, No. 1, 2012, pp. 42-45.

[46]   D. E. Breithaupt and A. Bamedi, “Carotenoid Esters in Vegetables and Fruits: A Screening with Emphasis on βCryptoxanthin Esters,” Journal of Agricultural and Food Chemistry, Vol. 49, No. 4, 2001, pp. 2064-2070. Hdoi:10.1021/jf001276t

[47]   T. Wingerath, W. Stahl and H. Sies, “β-Cryptoxanthin Selectively Increases in Human Chylomicrons upon Ingestion of Tangerine Concentrate Rich in β-Cryptoxanthin Esters,” Archives of Biochemistry and Biophysics, Vol. 324, No. 2, 1995, pp. 385-390. Hdoi:10.1006/abbi.1995.0052

[48]   T. Wingerath, H. Sies and W. Stahl, “Xanthophyll Esters in Human Skin,” Archives of Biochemistry and Biophysics, Vol. 355, No. 2, 1998, pp. 271-274. Hdoi:10.1006/abbi.1998.0734

 
 
Top