Functional polarization of macrophages of rats with progesterone-induced obesity treated with melanin from the Antarctic yeast Nadsoniella nigra

Keywords: progesterone; obesity; melanin; peritoneal macrophages; M1 and M2 polarization

Abstract

Progesterone-induced obesity develops in women who use this drug for contraception and the menopause treatment, though its mechanisms remain poorly understood. We studied functional M1 and M2 polarizations of the abdominal cavity macrophages of rats with progesterone induced obesity during 28 days of administration. The effect of melanin from the Antarctic yeast Nadsoniella nigra (Chaetothyriales, Herpotrichiellaceae, Nadsoniella Issatsch, 1914) was investigated. The NO level was determined by the accumulation of nitrites, ROS level was estimated by the NBT-test, arginase activity was assayed by the reaction of L-arginine hydrolysis. The body weights of rats administrated progesterone increased by 27% and continued to increase one month after withdrawal of progesterone (55% higher than control). Melanin prevents the weight gain when administered during one month after progesterone withdrawal. The NO production by peritoneal macrophages of obese animals intensified by 31% indicating their polarization towards pro-inflammatory M1 type. Production of ROS did not change. A 14% increase in arginase activity was observed, indicating the inhibition of M2 (anti-inflammatory) polarization. In the progesterone withdrawal group all these rates significantly decreased, indicating a reduction in the functional activity of peritoneal macrophages’. Melanin decreased the NO and ROS production by 60% and 18% respectively in comparison with the progesterone group and unexpectedly reduced arginase activity. Our data provide evidence of the spread of inflammation in response to progesterone-induced obesity. Peritoneal macrophages are involved in the inflammation in obesity, undergoing polarization towards the pro-inflammatory phenotype. The long-term consequences of such inflammation include the continuation of weight gain and likely the development of systemic inflammation associated with the exhaustion of the functional capacity of peritoneal cavity macrophages. Melanin has an anti-obesity effect and exhibits anti-inflammatory properties preventing progesterone-induced weight gain and macrophage M1 polarization. This requires detailed elucidation and can be valuable in designing countermeasures to prevent obesity outcomes.

References

Belemets, N., Kobyliak, N., Virchenko, O., Falalyeyeva, T., Olena, T., Bodnar, P., Savchuk, O., Galenova, T., Caprnda, M., Rodrigo, L., Skladany, L., Delev, D., Opatrilova, R., Kruzliak, P., Beregova, T., & Ostapchenko, L. (2017). Effects of polyphenol compounds melanin on NAFLD/NASH prevention. Biomedicine and Pharmacotherapy, 88, 267–276.

Bogdanski, P., Suliburska, J., Szulinska, M., Stepien, M., Pupek-Musialik, D., & Jablecka, A. (2012). Green tea extract reduces blood pressure, inflammatory biomarkers, and oxidative stress and improves parameters associated with insulin resistance in obese, hypertensive patients. Nutrition Research, 32, 421–427.

Bonny, A. E., Lange, H. L. H., Rogers, L. K., Gothard, D. M., & Reed, M. D. (2014). A pilot study of depot medroxyprogesterone acetate pharmacokinetics and weight gain in adolescent females. Contraception, 89(5), 357–360.

Bonny, A. E., Ziegler, J., Harvey, R., Debanne, S. M., Secic, M., & Cromer, B. A. (2006). Weight gain in obese and nonobese adolescent girls initiating depot medroxyprogesterone, oral contraceptive pills, or no hormonal contraceptive method. Archives of Pediatrics and Adolescent Medicine, 160(1), 40–45.

Bullo, M., Garcia-Lorda, P., Megias, I., & Salas-Salvado, J. (2003). Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression. Obesity Research, 11(4), 525–531.

Chidrawar, V. R., Patel, K. N., Sheth, N. R., Shiromwar, S. S., & Trivedi, P. (2011). Antiobesity effect of Stellaria media against drug induced obesity in Swiss albino mice. Ayu, 32(4), 576–584.

Coquoz, A., Gruetter, C., & Stute, P. (2019). Impact of micronized progesterone on body weight, body mass index, and glucose metabolism: A systematic review. Climacteric, 22(2), 148–161.

Curat, C. A., Miranville, A., Sengenès, C., Diehl, M., Tonus, C., Busse, R., & Bouloumié, A. (2004). From blood monocytes to adipose tissue-resident macrophages: Induction of diapedesis by human mature adipocytes. Diabetes, 53(5), 1285–1292.

Durmus, U., Duran, C., & Ecirli, S. (2017). Visceral adiposity index levels in overweight and/or obese, and non-obese patients with polycystic ovary syndrome and its relationship with metabolic and inflammatory parameters. Journal of Endocrinological Investigation, 40(5), 487–497.

Eberlé, D., Hegarty, B., Bossard, P., Ferré, P., & Foufelle, F. (2004). SREBP transcription factors: Master regulators of lipid homeostasis. Biochimie, 86(11), 839–848.

Engeli, S., Feldpausch, M., Gorzelniak, K., Hartwig, F., Heintze, U., Janke, J., Möhlig, M., Pfeiffer, A. F., Luft, F. C., & Sharma, A. M. (2003). Association between adiponectin and mediators of inflammation in obese women. Diabetes, 52, 942–947.

Falalyeyeva, T. M., Tsyryuk, O. I., Chyizhanska, N. V., & Zharova, V. P., (2009). The influence of melanin isolated from Antarctic yeasts on cortisol blood level of rats in conditions of stress action. Ukrainian Antarctic Journal, 8, 391–394.

Fernández-Sánchez, A., Madrigal-Santillán, E., Bautista, M., Esquivel-Soto, J., Morales-González, A., Esquivel-Chirino, C., Durante-Montiel, I., Sánchez-Rivera, G., Valadez-Vega, C., & Morales-González, J. A. (2011), Inflammation, oxidative stress, and obesity. International Journal of Molecular Sciences, 12(5), 3117–3132.

Fujisaka, S., Usui, I., Bukhari, A., Ikutani, M., Oya, T., Kanatani, Y., Tsuneyama, K., Nagai, Y., Takatsu, K., Urakaze, M., Kobayashi, M., & Tobe, K. (2009). Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes, 58(11), 2574–2582.

Furukawa, S., Fujita, T., Shimabukuro, M., Iwaki, M., Yamada, Y., Nakajima, Y., Nakayama, O., Makishima, M., Matsuda, M., & Shimomura, I. (2004). Increased oxidative stress in obesity and its impact on metabolic syndrome. Journal of Clinical Investigation, 114(12), 1752–1761.

Ghosn, E. E., Cassado, A. A., Govoni, G. R., Fukuhara, T., Yang, Y., Monack, D. M., Bortoluci, K. R., Almeida, S. R., Herzenberg, L. A., & Herzenberg, L. A. (2010). Two physically, functionally, and developmentally distinct peritoneal macrophage subsets. Proceedings of the National Academy of Sciences, 107(6), 2568–2573.

Gil-Ortega, M., Stucchi, P., Guzmán-Ruiz, R., Cano, V., Arribas, S., González, M. C., Ruiz-Gayo, M., Fernández-Alfonso, M. S., & Somoza, B. (2010). Adaptative nitric oxide overproduction in perivascular adipose tissue during early diet-induced obesity. Endocrinology, 151(7), 3299–3306.

Golyshkіn, D. V., Falaleeva, T. M., Neporada, K. S., & Beregova, T. V. (2015). The influence of melanin on the gastric mucosa and hypothalamic-pituitary-adrenocortical axis under acute stress conditions. Physiological Journal, 61(2), 65–72.

Gundamaraju, R., Mulaplli, S. B., & Ramesh, C. (2012-13). Evaluation of anti-obesity activity of Lantana camara var Linn. by progesterone induced obesity on albino mice. International Journal of Pharmacognosy and Phytochemical Research, 4(4), 213–218.

Harford, K. A., Reynolds, C. M., McGillicuddy, F. C., & Roche, H. M. (2011). Fats, inflammation and insulin resistance: Insights to the role of macrophage and T-cell accumulation in adipose tissue. Proceedings of the Nutrition Society, 70(4), 408–417.

Heilbronn, L. K., & Campbell, L. V. (2008). Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity. Current Pharmaceutical Design, 14(12), 1225–1230.

Hildebrandt, B. A., Racine, S. E., Keel, P. K., Burt, S. A., Neale, M., Boker, S., Sisk, C. L., & Klump, K. L. (2015). The effects of ovarian hormones and emotional eating on changes in weight preoccupation across the menstrual cycle. International Journal of Eating Disorders, 48(5), 477–486.

Hrabák, A., Derzbach, L., Csuka, I., Bajor, T., & Körner, A. (2011). Role of nitric oxide (NO) metabolism and inflammatory mediators in childhood obesity. Inflammation Research, 60(11), 1061–1070.

Kaur, G., & Kulkarni, S. K. (2001). Subchronic studies on modulation of feeding behavior and body weight by neuroteroids in female mice. Methods and Findings in Experimental and Clinical Pharmacology, 23(3), 115–119.

Kern, P. A., Ranganathan, S., Li, C., Wood, L., & Ranganathan, G. (2001). Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. American Journal of Physiology-Endocrinology and Metabolism, 280(5), 745–751.

Klump, K. L., Keel, P. K., Racine, S. E., Burt, S. A., Neale, M., Sisk, C. L., Boker, S., & Hu, J. (2013). The interactive effects of estrogen and progesterone on changes in emotional eating across the menstrual cycle. Journal of Abnormal Psychology, 122(1), 131–137.

Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R. (2007). Obesity induces a phenotypic switch in adipose tissue macrophage polarization. The Journal of Clinical Investigation, 117(1), 175–184.

Marseglia, L., Manti, S., D’Angelo, G., Nicotera, A., Parisi, E., Di Rosa, G., Gitto, E., & Arrigo, T. (2014). Oxidative stress in obesity: A critical component in human diseases. International Journal of Molecular Sciences, 16(1), 378–400.

Narita, Y., Kitamura, H., Wakita, D., Sumida, K., Masuko, K., Terada, S., Nakano, K., & Nishimura, T. (2013). The key role of IL-6-arginase cascade for inducing dendritic cell-dependent CD4(+) T cell dysfunction in tumor-bearing mice. The Journal of Immunology, 190(2), 812–820.

Nathan, C. (2008). Epidemic inflammation: Pondering obesity. Molecular Medicine, 14(7–8), 485–492.

Page, S., Chandhoke, V., & Baranova, A. (2011). Melanin and melanogenesis in adipose tissue: Possible mechanisms for abating oxidative stress and inflammation? Obesity Reviews, 12(5), e21-31.

Pandey, K. B., & Rizvi, S. I. (2009). Plant polyphenols as dietary antioxidants in human health and disease. Oxidative Medicine and Cellular Longevity, 2(5), 270–278.

Permyakova, N. M., Zheltonozhskaya, T. B., Beregova, T. V., Falalyeyeva, T. M., & Grishchenko, L. N. (2016). Micellar nanocarriers for anticancer drug melanin. Molecular Crystals and Liquid Crystals, 640(1), 122–133.

Rath, M., Müller, I., Kropf, P., Closs, E. I., & Munder, M. (2014). Metabolism via arginase or nitric oxide synthase: Two competing arginine pathways in macrophages. Frontiers in Immunology, 5, 532.

Reddy, D. S., & Kulkarni, S. K. (1998). The role of GABA-A and mitochondrial diazepam-binding inhibitor receptors on the effects of neurosteroids on food intake in mice. Psychopharmacology, 137(4), 391–400.

Sell, H., & Eckel, J. (2010). Adipose tissue inflammation: Novel insight into the role of macrophages and lymphocytes. Current Opinion in Clinical Nutrition and Metabolic Care, 13(4), 366–370.

Shaw, O. M., Pool, B., Dalbeth, N., & Harper, J. L. (2014). The effect of diet-induced obesity on the inflammatory phenotype of non-adipose-resident macrophages in an in vivo model of gout. Rheumatology (Oxford), 53(10), 1901–1905.

Sica, A., & Mantovani, A. (2012). Macrophage plasticity and polarization: in vivo veritas. Journal of Clinical Investigation, 122(3), 787–795.

Skivka, L. M., Fedorchuk, O. G., Rudyk, M. P., Pozur, V. V., Khranovska, N. M., & Grom, M. Y. (2013). Antineoplastic drug NSC631570 modulates functions of hypoxic macrophages. Cytology and Genetics, 47, 70–82.

Suneetha, D., Divya Teja Banda, S., Ramesh, C., & Ali, F. (2013). Evaluation of anti-obesity activity of methanolic extract of Sapindus emarginatus by progesterone induced obesity on albino mice. International Journal of Pharmaceutical Sciences Reviews Research, 23(2), 164–169.

Takele, Y., Abebe, T., Weldegebreal, T., Hailu, A., Hailu, W., Hurissa, Z., Ali, J., Diro, E., Sisay, Y., Cloke, T., Modolell, M., Munder, M., Tacchini-Cottier, F., Müller, I., & Kropf, P. (2013). Arginase activity in the blood of patients with visceral leishmaniasis and HIV infection. PLoS Neglected Tropical Diseases, 7(1), e1977.

Tian, C., Ye, X., Zhang, R., Long, J., Ren, W., Ding, S., Liao, D., Jin, X., Wu, H., Xu, S., & Ying C. (2013). Green tea polyphenols reduced fat deposits in high fat-fed rats via erk1/2-PPARgamma-adiponectin pathway. PloS One, 8(1), e53796.

Trayhurn, P., Wang, B., & Wood, I. S. (2008). Hypoxia in adipose tissue: A basis for the dysregulation of tissue function in obesity? British Journal of Nutrition, 100(2), 227–235.

Vincent, H. K., Vincent, K. R., Bourguignon, C., & Braith, R. W. (2005). Obesity and postexercise oxidative stress in older women. Medicine and Science in Sports and Exercise, 37(2), 213–219.

Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. Jr. (2003). Obesity is associated with macrophage accumulation in adipose tissue. The Journal of Clinical Investigation, 112(12), 1796–1808.

Wood, I. S., de Heredia, F. P., Wang, B., & Trayhurn, P. (2009). Cellular hypoxia and adipose tissue dysfunction in obesity. Proceedings of the Nutrition Society, 68(4), 370–377.

Wu, D., Ren, Z., Pae, M., Han, S. N., & Meydani, S. N. (2013). Diet-induced obesity has a differential effect on adipose tissue and macrophage inflammatory responses of young and old mice. Biofactors, 39(3), 326–333.

Zhang, M., Zhou, Z., Wang, J., & Li, S. (2016). MiR-130b promotes obesity associated adipose tissue inflammation and insulin resistance in diabetes mice through alleviating M2 macrophage polarization via repression of PPAR-γ. Immunology Letters, 180, 1–8.

Published
2019-11-12
How to Cite
Konopelnuk, V. I., Kompanets, I. V., Svyatetska, V. M., Molozhavaya, O. S., & Ostapchenko , L. I. (2019). Functional polarization of macrophages of rats with progesterone-induced obesity treated with melanin from the Antarctic yeast Nadsoniella nigra . Regulatory Mechanisms in Biosystems, 10(4), 538-543. https://doi.org/10.15421/021979