Araştırma Makalesi
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Topiramatın 3T3-L1 Hücrelerinde Adiponektin Salınımı Üzerine Etkisi: Anti-obezite Mekanizmalarına Yönelik Bir İn Vitro Yaklaşım

Yıl 2025, Cilt: 4 Sayı: 3, 80 - 87, 30.09.2025
https://doi.org/10.59518/farabimedj.1702978

Öz

Bu çalışma, metabolik açıdan giderek daha fazla yararları ortaya çıkan farmakolojik bir ajan olan topiramatın adiposit farklılaşması ve adipokin salınımı üzerindeki etkilerini, özellikle 3T3-L1 adipositlerinde adiponektin düzeylerine odaklanarak araştırmayı amaçlamıştır. 3T3-L1 preadipositleri farklılaşmaya indüklenmiş ve ardından değişen konsantrasyonlarda (1–100 µM) topiramat ile muamele edilmiştir. Lipit birikimi, Oil Red O boyama yöntemi kullanılarak değerlendirilmiş; adiponektin düzeyleri ise 6, 12 ve 24. saatlerde ELISA ile ölçülmüştür. Hücre canlılığı MTT testi ile belirlenmiştir. Topiramat, 100 µM’a kadar olan konsantrasyonlarda sitotoksisite oluşturmadan anlamlı lipit birikimi sağlamış, en yüksek lipit depolanması 50 µM dozunda gözlenmiştir. Farklılaşmış hücrelerde, tedaviden sonraki 12. ve 24. saatlerde adiponektin salınımında anlamlı bir artış saptanmış (p<0.01) ve en yüksek düzeyler 24. saatte belirlenmiştir (p<0.001). Topiramat, adiposit olgunlaşmasını artırmakta ve adiponektin salınımını uyarmaktadır; bu da potansiyel insülin-duyarlılaştırıcı ve antiinflamatuvar etkilerine işaret etmektedir. Bulgular, topiramatın kilo düşürücü etkilerinin bir kısmını adiponektin aracılı mekanizmalar üzerinden gösterebileceğini ve metabolik hastalıkların tedavisinde potansiyel bir ajan olabileceğini ortaya koymaktadır.

Kaynakça

  • Abad-Jiménez Z, Vezza T. Obesity: a global health challenge demanding urgent action. Biomedicines. 2025;13(2):502.
  • Kirichenko TV, Markina YV, Bogatyreva AI, Tolstik TV, Varaeva YR, Starodubova AV. The role of adipokines in inflammatory mechanisms of obesity. Int J Mol Sci. 2022;23(23):14982.
  • ia Y, Lacombe M, Muller C, Milhas D. Adipose tissue and androgens: the ins and outs. Adipocyte. 2025;14(1):2508885.
  • Song Q, Xu P, Xiao Q, Zhang C, Mao Y. Crosstalk between white adipose tissue and skin: unraveling its role in psoriasis pathogenesis. Mol Med Rep. 2025;31(6):169.
  • Kushner RF, Shapiro M. Obesity: assessment and treatment across the care continuum. Ann Med. 2025;57(1):2521433.
  • Almpanidou S, Vachliotis ID, Goulas A, Polyzos SA. The potential role of adipokines and hepatokines in age-related ocular diseases. Metab Open. 2025;26:100365.
  • Supriya R, Tam BT, Yu AP, et al. Adipokines demonstrate the interacting influence of central obesity with other cardiometabolic risk factors of metabolic syndrome in Hong Kong Chinese adults. PLoS One. 2018;13(8):e0201585.
  • Lee S, Kwak HB. Role of adiponectin in metabolic and cardiovascular disease. J Exerc Rehabil. 2014;10(2):54-59.
  • Kulkarni C, Kumar S, Khatoon S, et al. Isovitexin, a natural adiponectin agonist, prevents glucocorticoid-induced osteosarcopenia. Endocrine. 2025;89(2):565-577.
  • Xiong GL, Gadde KM. Combination phentermine/topiramate for obesity treatment in primary care: a review. Postgrad Med. 2014;126(2):110-116.
  • De Simone G, Supuran CT. Antiobesity carbonic anhydrase inhibitors. Curr Top Med Chem. 2007;7(9):879-884.
  • Mentese A, Alver A, Sumer A, Demir S. Effects of homocysteine on adipocyte differentiation and CD36 gene expression in 3T3-L1 adipocytes. J Cell Commun Signal. 2016;10(1):55-60.
  • Ramírez-Zacarías JL, Castro-Muñozledo F, Kuri-Harcuch W. Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with Oil Red O. Histochemistry. 1992;97(6):493-497.
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63.
  • Xuan H, Li Z, Yan H, et al. Antitumor activity of Chinese propolis in human breast cancer MCF-7 and MDA-MB-231 cells. Evid Based Complement Alternat Med. 2014;2014:280120.
  • Baldelli S, Aiello G, Mansilla Di Martino E, et al. The role of adipose tissue and nutrition in the regulation of adiponectin. Nutrients. 2024;16(15):2436.
  • Alzubi A, Glowacki HX, Burns JL, et al. Dose-dependent effects of short-chain fatty acids on 3T3-L1 adipocyte adipokine secretion and metabolic function. Nutrients. 2025;17(3):571.
  • Kadowaki T, Yamauchi T, Kubota N, et al. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest. 2006;116(7):1784-1792.
  • Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell. 2014;156(1-2):20-44.
  • Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest. 2011;121(6):2094-2101.
  • Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341-1352.
  • Sümer A, Keha EE, Mentese A, Alver A. Effects of topiramate on adipocyte differentiation and gene expression of certain carbonic anhydrase isoenzymes. Turk J Biochem. 2020;45(2):217-223.
  • Pollard AE. New concepts in the roles of AMPK in adipocyte stem cell biology. Essays Biochem. 2024;68(3):349-361.
  • Scheidl TB, Wager JL, Thompson JA. Adipose tissue stromal cells: rheostats for adipose tissue function and metabolic disease risk. Can J Cardiol. 2025; Epub ahead of print.
  • Gao D, Bing C, Griffiths HR. Disrupted adipokine secretion and inflammatory responses in human adipocyte hypertrophy. Adipocyte. 2025;14(1):2485927.
  • Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11(2):85-97.
  • Choi HM, Doss HM, Kim KS. Multifaceted physiological roles of adiponectin in inflammation and diseases. Int J Mol Sci. 2020;21(4):1219.
  • Shan Y, Chen Y, Gu H, Wang Y, Sun Y. Regulatory basis of adipokines leptin and adiponectin in epilepsy: from signaling pathways to glucose metabolism. Neurochem Res. 2023;48(7):2017-2028.
  • Chen QW, Meng RT, Ko CY. Modulating oxidative stress and neurogenic inflammation: the role of topiramate in migraine treatment. Front Aging Neurosci. 2024;16:1455858.

The Effect of Topiramate on Adiponectin Secretion in 3T3-L1 Adipocytes: An In Vitro Approach to Anti-Obesity Mechanisms

Yıl 2025, Cilt: 4 Sayı: 3, 80 - 87, 30.09.2025
https://doi.org/10.59518/farabimedj.1702978

Öz

This study aimed to investigate the effects of topiramate, a pharmacological agent with emerging metabolic benefits on adipocyte differentiation and adipokine secretion, with a particular focus on adiponectin levels in 3T3-L1 adipocytes. 3T3-L1 preadipocytes were induced to differentiate and subsequently treated with varying concentrations of topiramate (1–100 µM). Lipid accumulation was evaluated using Oil Red O staining, while adiponectin levels were measured via ELISA at 6, 12, and 24 hours. Cell viability was assessed using the MTT assay. Topiramate promoted significant lipid accumulation without cytotoxicity at concentrations up to 100 µM, with the 50 µM dose showing the highest lipid deposition. A significant increase in adiponectin secretion was observed in differentiated cells at 12 and 24 hours post-treatment (p<0.01), with the highest levels detected at 24 hours (p<0.001). Topiramate enhances adipocyte maturation and stimulates adiponectin secretion, indicating potential insulin-sensitizing and anti-inflammatory effects. These findings suggest that topiramate may exert part of its anti-obesity effects through adiponectin-mediated mechanisms and highlight its potential as a therapeutic agent in metabolic disease management.

Etik Beyan

This study does not require ethical approval as it is a computational study.

Kaynakça

  • Abad-Jiménez Z, Vezza T. Obesity: a global health challenge demanding urgent action. Biomedicines. 2025;13(2):502.
  • Kirichenko TV, Markina YV, Bogatyreva AI, Tolstik TV, Varaeva YR, Starodubova AV. The role of adipokines in inflammatory mechanisms of obesity. Int J Mol Sci. 2022;23(23):14982.
  • ia Y, Lacombe M, Muller C, Milhas D. Adipose tissue and androgens: the ins and outs. Adipocyte. 2025;14(1):2508885.
  • Song Q, Xu P, Xiao Q, Zhang C, Mao Y. Crosstalk between white adipose tissue and skin: unraveling its role in psoriasis pathogenesis. Mol Med Rep. 2025;31(6):169.
  • Kushner RF, Shapiro M. Obesity: assessment and treatment across the care continuum. Ann Med. 2025;57(1):2521433.
  • Almpanidou S, Vachliotis ID, Goulas A, Polyzos SA. The potential role of adipokines and hepatokines in age-related ocular diseases. Metab Open. 2025;26:100365.
  • Supriya R, Tam BT, Yu AP, et al. Adipokines demonstrate the interacting influence of central obesity with other cardiometabolic risk factors of metabolic syndrome in Hong Kong Chinese adults. PLoS One. 2018;13(8):e0201585.
  • Lee S, Kwak HB. Role of adiponectin in metabolic and cardiovascular disease. J Exerc Rehabil. 2014;10(2):54-59.
  • Kulkarni C, Kumar S, Khatoon S, et al. Isovitexin, a natural adiponectin agonist, prevents glucocorticoid-induced osteosarcopenia. Endocrine. 2025;89(2):565-577.
  • Xiong GL, Gadde KM. Combination phentermine/topiramate for obesity treatment in primary care: a review. Postgrad Med. 2014;126(2):110-116.
  • De Simone G, Supuran CT. Antiobesity carbonic anhydrase inhibitors. Curr Top Med Chem. 2007;7(9):879-884.
  • Mentese A, Alver A, Sumer A, Demir S. Effects of homocysteine on adipocyte differentiation and CD36 gene expression in 3T3-L1 adipocytes. J Cell Commun Signal. 2016;10(1):55-60.
  • Ramírez-Zacarías JL, Castro-Muñozledo F, Kuri-Harcuch W. Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with Oil Red O. Histochemistry. 1992;97(6):493-497.
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63.
  • Xuan H, Li Z, Yan H, et al. Antitumor activity of Chinese propolis in human breast cancer MCF-7 and MDA-MB-231 cells. Evid Based Complement Alternat Med. 2014;2014:280120.
  • Baldelli S, Aiello G, Mansilla Di Martino E, et al. The role of adipose tissue and nutrition in the regulation of adiponectin. Nutrients. 2024;16(15):2436.
  • Alzubi A, Glowacki HX, Burns JL, et al. Dose-dependent effects of short-chain fatty acids on 3T3-L1 adipocyte adipokine secretion and metabolic function. Nutrients. 2025;17(3):571.
  • Kadowaki T, Yamauchi T, Kubota N, et al. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest. 2006;116(7):1784-1792.
  • Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell. 2014;156(1-2):20-44.
  • Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest. 2011;121(6):2094-2101.
  • Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341-1352.
  • Sümer A, Keha EE, Mentese A, Alver A. Effects of topiramate on adipocyte differentiation and gene expression of certain carbonic anhydrase isoenzymes. Turk J Biochem. 2020;45(2):217-223.
  • Pollard AE. New concepts in the roles of AMPK in adipocyte stem cell biology. Essays Biochem. 2024;68(3):349-361.
  • Scheidl TB, Wager JL, Thompson JA. Adipose tissue stromal cells: rheostats for adipose tissue function and metabolic disease risk. Can J Cardiol. 2025; Epub ahead of print.
  • Gao D, Bing C, Griffiths HR. Disrupted adipokine secretion and inflammatory responses in human adipocyte hypertrophy. Adipocyte. 2025;14(1):2485927.
  • Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11(2):85-97.
  • Choi HM, Doss HM, Kim KS. Multifaceted physiological roles of adiponectin in inflammation and diseases. Int J Mol Sci. 2020;21(4):1219.
  • Shan Y, Chen Y, Gu H, Wang Y, Sun Y. Regulatory basis of adipokines leptin and adiponectin in epilepsy: from signaling pathways to glucose metabolism. Neurochem Res. 2023;48(7):2017-2028.
  • Chen QW, Meng RT, Ko CY. Modulating oxidative stress and neurogenic inflammation: the role of topiramate in migraine treatment. Front Aging Neurosci. 2024;16:1455858.
Toplam 29 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Metabolik Tıp
Bölüm Araştırma Makaleleri
Yazarlar

Ayşegül Sümer 0000-0003-4918-4368

Yayımlanma Tarihi 30 Eylül 2025
Gönderilme Tarihi 20 Mayıs 2025
Kabul Tarihi 1 Eylül 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 4 Sayı: 3

Kaynak Göster

AMA Sümer A. The Effect of Topiramate on Adiponectin Secretion in 3T3-L1 Adipocytes: An In Vitro Approach to Anti-Obesity Mechanisms. Farabi Med J. Eylül 2025;4(3):80-87. doi:10.59518/farabimedj.1702978

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