Verbascoside, 3T3-L1 hipertrofik hücrelerinde lipolizle ilişkili genlerin ekspresyonunda değişiklik yoluyla lipolizi artırır
Yıl 2026,
Cilt: 19 Sayı: 1, 2 - 2
Neslihan Esra Özbek
,
Emine Kılıç Toprak
,
Ayşegül Çört
,
Fatih Altıntaş
,
Onur Tokgün
,
Vural Küçükatay
Öz
Amaç: Son zamanlarda yapılan çalışmalar, obezite ile mücadele için yağ yakıcı özelliklere sahip doğal, toksik olmayan polifenollerin kullanımında umut verici sonuçlar göstermiştir. Bu çalışmanın amacı, Verbascoside (VB) tedavisine yanıt olarak hipertrofik 3T3-L1 adipositlerin gen ekspresyon profilindeki değişiklikleri ve yağ metabolizmasında önemli rol oynayan 5' AMP ile aktive olan protein kinaz (AMPK), peroksizom proliferatör ile aktive olan reseptör gama (PPAR-γ), hormona duyarlı lipaz (HSL) ve lipid damlacığı ile ilişkili protein (perilipin1, PLIN1) mRNA seviyelerini araştırmaktır.
Gereç ve yöntemler: Bu amaçla, 3T3-L1 preadipositleri farklılaştırıldı ve hipertrofiye edildi. Hücrelerdeki trigliserit birikimi Oil Red O boyaması kullanılarak değerlendirildi. Hipertrofik 3T3-L1 hücreleri 48 saat boyunca VB ile inkübe edildi.
Bulgular: Bu sürenin sonunda yapılan mikroarray analizi, VB'nin lipoliz süreçlerinde yer alan birçok proteinin mRNA seviyelerini artırdığını, ancak PPARγ, AMPK, HSL ve PLIN1 ekspresyonunu değiştirmediğini gösterdi. Bunu doğrulamak için yaptığımız RT-PCR’a göre PPARγ, AMPK, HSL ve PLIN1 ekspresyon seviyelerinin VB tedavisi ile değiştiğini belirledik. Sonuçlarımız, VB uygulamasının lipolitik süreçlerde yer alan genlerin ifadesinde kontrole kıyasla önemli bir artışa neden olduğunu göstermiştir.
Sonuç: Bu çalışmanın bulguları, VB'nin lipolitik süreçlerde yer alan önemli hücre içi proteinler aracılığıyla aktif bir rol oynayabileceğini göstermektedir.
Proje Numarası
2020TIPF011
Kaynakça
-
Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med. 2013;19(10):1252-1263. doi:10.1038/nm.3361
-
Seale P, Lazar MA. Brown fat in humans: turning up the heat on obesity. Diabetes. 2009;58:1482-1484. doi:10.2337/db09-0622
-
Reddy NL, Tan BK, Barber TM, Randeva HS. Brown adipose tissue: endocrine determinants of function and therapeutic manipulation as a novel treatment strategy for obesity. BMC Obes. 2014;1:13. doi:10.1186/s40608-014-0013-5
-
Swinburn BA, Sacks G, Hall KD, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011;378(9793):804-814. doi:10.1016/S0140-6736(11)60813-1
-
Kawai T, Autieri MV, Scalia R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am J Physiol Cell Physiol. 2021;320(3):C375-C391. doi:10.1152/ajpcell.00580.2020
-
Wadden TA, Tronieri JS, Butryn ML. Lifestyle modification approaches for the treatment of obesity in adults. Am Psychol. 2020;75(2):235-251. doi:10.1037/amp0000517
-
Torres Fuentes C, Schellekens H, Dinan TG, Cryan JF. A natural solution for obesity: bioactives for the prevention and treatment of weight gain. A review. Nutr Neurosci. 2015;18(2):49-65. doi:10.1179/1476830513Y.000000099
-
Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society [published correction appears in Circulation. 2014 Jun 24;129(25 Suppl 2):S139-40]. Circulation. 2014;129(25 Suppl 2):S102-S138. doi:10.1161/01.cir.0000437739.71477.ee
-
Sjöström L, Narbro K, Sjöström CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741-752. doi:10.1056/NEJMoa066254
-
Bessesen DH, Van Gaal LF. Progress and challenges in anti-obesity pharmacotherapy. Lancet Diabetes Endocrinol. 2018;6(3):237-248. doi:10.1016/S2213-8587(17)30236-X
-
Sjöström L, Peltonen M, Jacobson P, et al. Bariatric surgery and long-term cardiovascular events. JAMA. 2012;307(1):56-65. doi:10.1001/jama.2011.1914
-
Wu L, Georgiev MI, Cao H, et al. Therapeutic potential of phenylethanoid glycosides: A systematic review. Med Res Rev. 2020;40(6):2605-2649. doi:10.1002/med.21717
-
Jiménez C, Riguera R. Phenylethanoid glycosides in plants: structure and biological activity. Nat Prod Rep. 1994;11(6):591-606. doi:10.1039/NP9941100591
-
Pennacchio M, Syah YM, Ghisalberti EL, Alexander E. Cardioactive compounds from Eremophila species. J Ethnopharmacol. 1996;53(1):21-27. doi:10.1016/0378-8741(96)01444-2
-
Herranz López M, Barrajón Catalán E, Segura Carretero A, Menéndez JA, Joven J, Micol V. Lemon verbena (Lippia citriodora) polyphenols alleviate obesity-related disturbances in hypertrophic adipocytes through AMPK-dependent mechanisms. Phytomedicine. 2015;22(6):605-614. doi:10.1016/j.phymed.2015.03.010
-
Di Giancamillo A, Rossi R, Pastorelli G, et al. The effects of dietary verbascoside on blood and liver oxidative stress status induced by a high n-6 polyunsaturated fatty acids diet in piglets. J Anim Sci. 2015;93(6):2849-2859. doi:10.2527/jas.2014-8607
-
Galli A, Marciani P, Marku A, et al. Verbascoside protects pancreatic β-cells against ER-stress. Biomedicines. 2020;8(12):582. doi:10.3390/biomedicines8120582
-
Alipieva K, Korkina L, Orhan IE, Georgiev MI. Verbascoside—a review of its occurrence, (bio)synthesis and pharmacological significance. Biotechnol Adv. 2014;32(6):1065-1076. doi:10.1016/j.biotechadv.2014.07.001
-
Wu X, He W, Zhang H, Li Y, Liu Z, He Z. Acteoside: a lipase inhibitor from the Chinese tea Ligustrum purpurascens kudingcha. Food Chem. 2014;142:306-310. doi:10.1016/j.foodchem.2013.07.071
-
Olivares Vicente M, Sánchez Marzo N, Encinar JA, et al. The potential synergistic modulation of AMPK by Lippia citriodora compounds as a target in metabolic disorders. Nutrients. 2019;11(12):2961. doi:10.3390/nu11122961
-
Lee YS, Yang WK, Kim HY, et al. Metabolaid® combination of lemon verbena and hibiscus flower extract prevents high-fat diet-induced obesity through AMP-activated protein kinase activation. Nutrients. 2018;10(9):1204. doi:10.3390/nu10091204
-
Green H, Kehinde O. An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell. 1975;5(1):19-27. doi:10.1016/0092-8674(75)90087-2
-
Etienne W, Meyer MH, Peppers J, Meyer RA Jr. Comparison of mRNA gene expression by RT-PCR and DNA microarray. Biotechniques. 2004;36(4):618-626. doi:10.2144/04364ST02
-
Olivares Vicente M, Sánchez Marzo N, Encinar JA, et al. The potential synergistic modulation of AMPK by Lippia citriodora compounds as a target in metabolic disorders. Nutrients. 2019;11(12):2961. doi:10.3390/nu11122961
-
Jiménez Sánchez C, Olivares Vicente M, Rodríguez Pérez C, et al. AMPK modulatory activity of olive-tree leaves phenolic compounds: Bioassay-guided isolation on adipocyte model and in silico approach. PLoS One. 2017;12(3):e0173074. doi:10.1371/journal.pone.0173074
-
Silvester AJ, Aseer KR, Yun JW. Dietary polyphenols and their roles in fat browning. J Nutr Biochem. 2019;64:1-12. doi:10.1016/j.jnutbio.2018.09.028
-
Etienne W, Meyer MH, Peppers J, Meyer RA Jr. Comparison of mRNA gene expression by RT-PCR and DNA microarray. Biotechniques. 2004;36(4):618-620, 622, 624-626. doi:10.2144/04364ST02
-
Gauthier C, Rozec B, Manoury B, Balligand JL. Beta-3 adrenoceptors as new therapeutic targets for cardiovascular pathologies. Curr Heart Fail Rep. 2011;8(3):184-192. doi:10.1007/s11897-011-0064-6
-
Ghorbani M, Claus TH, Himms Hagen J. Hypertrophy of brown adipocytes in brown and white adipose tissues and reversal of diet-induced obesity in rats treated with a β3-adrenoceptor agonist. Biochem Pharmacol. 1997;54(1):121-131. doi:10.1016/S0006-2952(97)00162-7
-
Festuccia WT, Laplante M, Berthiaume M, Gélinas Y, Deshaies Y. PPARgamma agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control. Diabetologia. 2006;49(10):2427-2436. doi:10.1007/s00125-006-0336-y
-
Kuryłowicz A, Puzianowska Kuźnicka M. Induction of adipose tissue browning as a strategy to combat obesity. Int J Mol Sci. 2020;21(17):6241. doi:10.3390/ijms21176241
-
Jeon SM. Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016;48(7):e245. doi:10.1038/emm.2016.81
-
Pulinilkunnil T, He H, Kong D, et al. Adrenergic regulation of AMP-activated protein kinase in brown adipose tissue in vivo. J Biol Chem. 2011;286(11):8798-8809. doi:10.1074/jbc.M111.218719
-
Mottillo EP, Xiang JS, Granneman JG. Role of hormone-sensitive lipase in beta-adrenergic remodeling of white adipose tissue. Am J Physiol Endocrinol Metab. 2007;293:E1188-E1197. doi:10.1152/ajpendo.00211.2007
-
Yeaman SJ. Hormone-sensitive lipase--new roles for an old enzyme. Biochem J. 2004;379(Pt 1):11-22. doi:10.1042/BJ20031811
-
Desgrouas C, Thalheim T, Cerino M, Badens C, Bonello Palot N. Perilipin 1: a systematic review on its functions on lipid metabolism and atherosclerosis in mice and humans. Cardiovasc Res. 2024;120(3):237-248. doi:10.1093/cvr/cvae005
-
Londos C, Brasaemle DL, Schultz CJ, Segrest JP, Kimmel AR. Perilipins, ADRP, and other proteins that associate with intracellular neutral lipid droplets in animal cells. Semin Cell Dev Biol. 1999;10(1):51-58. doi:10.1006/scdb.1998.0275
-
Brasaemle DL, Rubin B, Harten IA, Gruia Gray J, Kimmel AR, Londos C. Perilipin A increases triacylglycerol storage by decreasing the rate of triacylglycerol hydrolysis. J Biol Chem. 2000;275(49):38486-38493. doi:10.1074/jbc.M007322200
-
Lafontan M, Langin D. Lipolysis and lipid mobilization in human adipose tissue. Prog Lipid Res. 2009;48(5):275-297. doi:10.1016/j.plipres.2009.05.001
-
Iena FM, Lebeck J. Implications of Aquaglyceroporin 7 in Energy Metabolism. Int J Mol Sci. 2018;19(1):154. doi:10.3390/ijms19010154
Verbascoside promotes lipolysis in 3T3-L1 hypertrophic cells through alteration in the expression of lipolysis-related genes
Yıl 2026,
Cilt: 19 Sayı: 1, 2 - 2
Neslihan Esra Özbek
,
Emine Kılıç Toprak
,
Ayşegül Çört
,
Fatih Altıntaş
,
Onur Tokgün
,
Vural Küçükatay
Öz
Purpose: Recent studies have shown promising outcomes in the utilization of natural, non-toxic polyphenols with fat-burning properties to combat obesity. The aim of this study was to investigate the changes in the gene expression profile of hypertrophic 3T3-L1 adipocytes in response to Verbascoside (VB) treatment and the mRNA levels of 5' AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPAR-γ), hormone-sensitive lipase (HSL), and lipid droplet-associated protein (perilipin1, PLIN1), which play an important role in fat metabolism.
Materials and methods: For this purpose, 3T3-L1 preadipocytes were differentiated and hypertrophied. Triglyceride accumulation in the cells was evaluated using Oil Red O staining. The hypertrophic 3T3-L1 cells were incubated with VB for 48 h.
Results: Microarray analysis at the end of this period showed that VB increased the mRNA levels of many proteins involved in lipolysis processes, but did not change the expression of PPARγ, AMPK, HSL and PLIN1. Therefore, we confirmed by RT-PCR that PPARγ, AMPK, HSL, and PLIN1 expression levels were altered by VB treatment. Our results showed that VB treatment caused a significant increase in the expression of genes involved in lipolytic processes compared to the control.
Conclusion: The findings of this study suggest that VB may play an active role through important intracellular proteins involved in lipolytic processes.
Proje Numarası
2020TIPF011
Kaynakça
-
Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med. 2013;19(10):1252-1263. doi:10.1038/nm.3361
-
Seale P, Lazar MA. Brown fat in humans: turning up the heat on obesity. Diabetes. 2009;58:1482-1484. doi:10.2337/db09-0622
-
Reddy NL, Tan BK, Barber TM, Randeva HS. Brown adipose tissue: endocrine determinants of function and therapeutic manipulation as a novel treatment strategy for obesity. BMC Obes. 2014;1:13. doi:10.1186/s40608-014-0013-5
-
Swinburn BA, Sacks G, Hall KD, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011;378(9793):804-814. doi:10.1016/S0140-6736(11)60813-1
-
Kawai T, Autieri MV, Scalia R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am J Physiol Cell Physiol. 2021;320(3):C375-C391. doi:10.1152/ajpcell.00580.2020
-
Wadden TA, Tronieri JS, Butryn ML. Lifestyle modification approaches for the treatment of obesity in adults. Am Psychol. 2020;75(2):235-251. doi:10.1037/amp0000517
-
Torres Fuentes C, Schellekens H, Dinan TG, Cryan JF. A natural solution for obesity: bioactives for the prevention and treatment of weight gain. A review. Nutr Neurosci. 2015;18(2):49-65. doi:10.1179/1476830513Y.000000099
-
Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society [published correction appears in Circulation. 2014 Jun 24;129(25 Suppl 2):S139-40]. Circulation. 2014;129(25 Suppl 2):S102-S138. doi:10.1161/01.cir.0000437739.71477.ee
-
Sjöström L, Narbro K, Sjöström CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741-752. doi:10.1056/NEJMoa066254
-
Bessesen DH, Van Gaal LF. Progress and challenges in anti-obesity pharmacotherapy. Lancet Diabetes Endocrinol. 2018;6(3):237-248. doi:10.1016/S2213-8587(17)30236-X
-
Sjöström L, Peltonen M, Jacobson P, et al. Bariatric surgery and long-term cardiovascular events. JAMA. 2012;307(1):56-65. doi:10.1001/jama.2011.1914
-
Wu L, Georgiev MI, Cao H, et al. Therapeutic potential of phenylethanoid glycosides: A systematic review. Med Res Rev. 2020;40(6):2605-2649. doi:10.1002/med.21717
-
Jiménez C, Riguera R. Phenylethanoid glycosides in plants: structure and biological activity. Nat Prod Rep. 1994;11(6):591-606. doi:10.1039/NP9941100591
-
Pennacchio M, Syah YM, Ghisalberti EL, Alexander E. Cardioactive compounds from Eremophila species. J Ethnopharmacol. 1996;53(1):21-27. doi:10.1016/0378-8741(96)01444-2
-
Herranz López M, Barrajón Catalán E, Segura Carretero A, Menéndez JA, Joven J, Micol V. Lemon verbena (Lippia citriodora) polyphenols alleviate obesity-related disturbances in hypertrophic adipocytes through AMPK-dependent mechanisms. Phytomedicine. 2015;22(6):605-614. doi:10.1016/j.phymed.2015.03.010
-
Di Giancamillo A, Rossi R, Pastorelli G, et al. The effects of dietary verbascoside on blood and liver oxidative stress status induced by a high n-6 polyunsaturated fatty acids diet in piglets. J Anim Sci. 2015;93(6):2849-2859. doi:10.2527/jas.2014-8607
-
Galli A, Marciani P, Marku A, et al. Verbascoside protects pancreatic β-cells against ER-stress. Biomedicines. 2020;8(12):582. doi:10.3390/biomedicines8120582
-
Alipieva K, Korkina L, Orhan IE, Georgiev MI. Verbascoside—a review of its occurrence, (bio)synthesis and pharmacological significance. Biotechnol Adv. 2014;32(6):1065-1076. doi:10.1016/j.biotechadv.2014.07.001
-
Wu X, He W, Zhang H, Li Y, Liu Z, He Z. Acteoside: a lipase inhibitor from the Chinese tea Ligustrum purpurascens kudingcha. Food Chem. 2014;142:306-310. doi:10.1016/j.foodchem.2013.07.071
-
Olivares Vicente M, Sánchez Marzo N, Encinar JA, et al. The potential synergistic modulation of AMPK by Lippia citriodora compounds as a target in metabolic disorders. Nutrients. 2019;11(12):2961. doi:10.3390/nu11122961
-
Lee YS, Yang WK, Kim HY, et al. Metabolaid® combination of lemon verbena and hibiscus flower extract prevents high-fat diet-induced obesity through AMP-activated protein kinase activation. Nutrients. 2018;10(9):1204. doi:10.3390/nu10091204
-
Green H, Kehinde O. An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell. 1975;5(1):19-27. doi:10.1016/0092-8674(75)90087-2
-
Etienne W, Meyer MH, Peppers J, Meyer RA Jr. Comparison of mRNA gene expression by RT-PCR and DNA microarray. Biotechniques. 2004;36(4):618-626. doi:10.2144/04364ST02
-
Olivares Vicente M, Sánchez Marzo N, Encinar JA, et al. The potential synergistic modulation of AMPK by Lippia citriodora compounds as a target in metabolic disorders. Nutrients. 2019;11(12):2961. doi:10.3390/nu11122961
-
Jiménez Sánchez C, Olivares Vicente M, Rodríguez Pérez C, et al. AMPK modulatory activity of olive-tree leaves phenolic compounds: Bioassay-guided isolation on adipocyte model and in silico approach. PLoS One. 2017;12(3):e0173074. doi:10.1371/journal.pone.0173074
-
Silvester AJ, Aseer KR, Yun JW. Dietary polyphenols and their roles in fat browning. J Nutr Biochem. 2019;64:1-12. doi:10.1016/j.jnutbio.2018.09.028
-
Etienne W, Meyer MH, Peppers J, Meyer RA Jr. Comparison of mRNA gene expression by RT-PCR and DNA microarray. Biotechniques. 2004;36(4):618-620, 622, 624-626. doi:10.2144/04364ST02
-
Gauthier C, Rozec B, Manoury B, Balligand JL. Beta-3 adrenoceptors as new therapeutic targets for cardiovascular pathologies. Curr Heart Fail Rep. 2011;8(3):184-192. doi:10.1007/s11897-011-0064-6
-
Ghorbani M, Claus TH, Himms Hagen J. Hypertrophy of brown adipocytes in brown and white adipose tissues and reversal of diet-induced obesity in rats treated with a β3-adrenoceptor agonist. Biochem Pharmacol. 1997;54(1):121-131. doi:10.1016/S0006-2952(97)00162-7
-
Festuccia WT, Laplante M, Berthiaume M, Gélinas Y, Deshaies Y. PPARgamma agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control. Diabetologia. 2006;49(10):2427-2436. doi:10.1007/s00125-006-0336-y
-
Kuryłowicz A, Puzianowska Kuźnicka M. Induction of adipose tissue browning as a strategy to combat obesity. Int J Mol Sci. 2020;21(17):6241. doi:10.3390/ijms21176241
-
Jeon SM. Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016;48(7):e245. doi:10.1038/emm.2016.81
-
Pulinilkunnil T, He H, Kong D, et al. Adrenergic regulation of AMP-activated protein kinase in brown adipose tissue in vivo. J Biol Chem. 2011;286(11):8798-8809. doi:10.1074/jbc.M111.218719
-
Mottillo EP, Xiang JS, Granneman JG. Role of hormone-sensitive lipase in beta-adrenergic remodeling of white adipose tissue. Am J Physiol Endocrinol Metab. 2007;293:E1188-E1197. doi:10.1152/ajpendo.00211.2007
-
Yeaman SJ. Hormone-sensitive lipase--new roles for an old enzyme. Biochem J. 2004;379(Pt 1):11-22. doi:10.1042/BJ20031811
-
Desgrouas C, Thalheim T, Cerino M, Badens C, Bonello Palot N. Perilipin 1: a systematic review on its functions on lipid metabolism and atherosclerosis in mice and humans. Cardiovasc Res. 2024;120(3):237-248. doi:10.1093/cvr/cvae005
-
Londos C, Brasaemle DL, Schultz CJ, Segrest JP, Kimmel AR. Perilipins, ADRP, and other proteins that associate with intracellular neutral lipid droplets in animal cells. Semin Cell Dev Biol. 1999;10(1):51-58. doi:10.1006/scdb.1998.0275
-
Brasaemle DL, Rubin B, Harten IA, Gruia Gray J, Kimmel AR, Londos C. Perilipin A increases triacylglycerol storage by decreasing the rate of triacylglycerol hydrolysis. J Biol Chem. 2000;275(49):38486-38493. doi:10.1074/jbc.M007322200
-
Lafontan M, Langin D. Lipolysis and lipid mobilization in human adipose tissue. Prog Lipid Res. 2009;48(5):275-297. doi:10.1016/j.plipres.2009.05.001
-
Iena FM, Lebeck J. Implications of Aquaglyceroporin 7 in Energy Metabolism. Int J Mol Sci. 2018;19(1):154. doi:10.3390/ijms19010154