Research Article


DOI :10.26650/experimed.1489790   IUP :10.26650/experimed.1489790    Full Text (PDF)

Capsaicin Modulates Adipocyte Cell Differentiation and Inflammatory Gene Expression

Sevgin DeğirmencioğluPınar ÇetinalpMuhammed SeyithanoğluSevda Tanrıkulu KüçükHikmet KoçakYıldız Öner İyidoğan

Objective: Adipose tissue stores lipids necessary for the maintenance of nutritional homeostasis. It is also an endocrine organ that reacts to changes in inflammation and energy status. Capsaicin, the principal bioactive compound in red pepper, has garnered significant attention for its reported anti-obesity, anti-diabetic, anti-oxidant, and anti-inflammatory properties. In this study, we aimed to elucidate the influence and most efficacious dose of capsaicin on the expression of lipid metabolism-related inflammatory proteins and the inhibition of adipocyte cell differentiation.

Materials and Methods: Cell viability analysis was performed using CCK-8, cell differentiation was assessed using Oil Red O, and gene expression levels of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), adiponectin, leptin, cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), nuclear factor kappa B1 (NF-κB1), tumor necrosis factor-alpha (TNF-α), sirtuin-1 (SIRT-1), transient receptor potential vanilloid receptor 1 (TRPV1), and uncoupling protein 2 (UCP2) were evaluated using quantitative real time polymerase chain reaction (qRT-PCR). Statistical analyses were conducted using GraphPad Prism 5. One-way ANOVA was performed to compare quantitative data between the groups.

Results: Capsaicin suppressed preadipocyte-to-adipocyte differentiation and mitigated the release of pro-inflammatory cytokines, particularly at low concentrations. Capsaicin effectively suppressed adiponectin levels at all concentrations but decreased leptin levels at lower concentrations (0.5 µM and 1 µM). Capsaicin stimulated the expressions of SIRT1 and TRPV-1 in adipocytes. According to our findings, the most effective capsaicin dose for the regulation of SIRT1 and TRPV-1 expressions appears to be 20 μM.

Conclusion: Capsaicin’s effect on proteins regulating adipogenesis is not dose-related, but its inhibitory effect on adiposity-dependent inflammation was more pronounced at low concentrations.


PDF View

References

  • 1. Ntambi JM, Young-Cheul K. Adipocyte differentiation and gene expression. J Nutr 2000; 130(12): 3122S-26S. google scholar
  • 2. Varghese S, Kubatka P, Rodrigo L, Gazdikova K, Caprnda M, Fedotova J, et al. Chili pepper as a body weight-loss food. Int J Food Sci Nutr 2017; 68(4): 392-401. google scholar
  • 3. Whiting S, Derbyshire E, Tiwari BK. Capsaicinoids and capsinoids. A potential role for weight management? A systematic review of the evidence. Appetite 2012; 59(2): 341-8. google scholar
  • 4. Chen J, Li L, Li Y, Liang X, Sun Q, Yu H, et al. Activation of TRPV1 channel by dietary capsaicin improves visceral fat remodeling through connexin43-mediated Ca2+ influx. Cardiovasc Diabetol 2015; 14:22. google scholar
  • 5. Sun F, Xiong S, Zhu Z. Dietary capsaicin protects cardiometabolic organs from dysfunction. Nutrients 2016; 8(5): 174. google scholar
  • 6. Zheng J, Zheng S, Feng Q, Zhang Q, Xiao X. Dietary capsaicin and its anti-obesity potency: from mechanism to clinical implications. Biosci Rep 2017; 37(3): BSR20170286. google scholar
  • 7. Baskaran P, Krishnan V, Ren J, Thyagarajan B. Capsaicin induces browning of white adipose tissue and counters obesity by activating TRPV1 channel-dependent mechanisms. Br J Pharmacol 2016; 173(15): 2369-89. google scholar
  • 8. Kang JH, Kim CS, Han IS, Kawada T, Yu R. Capsaicin, a spicy component of hot peppers, modulates adipokine gene expression and protein release from obese-mouse adipose tissues and isolated adipocytes, and suppresses the inflammatory responses of adipose tissue macrophages. FEBS Lett 2007; 581(23): 4389-96. google scholar
  • 9. Hsu CL, Yen GC. Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 cells. J Agric Food Chem 2007; 55(5): 1730-6. google scholar
  • 10. Mahadik SR, Lele RD, Saranath D, Seth A, Parikh V. Uncoupling protein-2 (UCP2) gene expression in subcutaneous and omental adipose tissue of Asian Indians: Relationship to adiponectin and parameters of metabolic syndrome. Adipocyte 2012; 1(2): 101-7. google scholar
  • 11. Oberkofler H, Liu YM, Esterbauer H, Hell E, Krempler F, Patsch W. Uncoupling protein-2 gene: reduced mRNA expression in intraperitoneal adipose tissue of obese humans. Diabetologia 1998; 41(8): 940-6. google scholar
  • 12. Zamora-Mendoza R, Rosas-Vargas H, Ramos-Cervantes MT, Garcia-Zuniga P, Perez-Lorenzana H, Mendoza-Lorenzo P, et al. Dysregulation of mitochondrial function and biogenesis modulators in adipose tissue of obese children. Int J Obes (Lond) 2018; 42(4): 618-24. google scholar
  • 13. Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature 2017; 542(7640): 177-85. google scholar
  • 14. Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Invest 2011; 121(6): 2111-7. google scholar
  • 15. Mraz M, Haluzik M. The role of adipose tissue immune cells in obesity and low-grade inflammation. J Endocrinol 2014; 222(3): R113-27. google scholar
  • 16. Baboota RK, Singh DP, Sarma SM, Kaur J, Sandhir R, Boparai RK, et al. Capsaicin induces “brite” phenotype in differentiating 3T3-L1 preadipocytes. PLoS One 2014; 9: 7. google scholar
  • 17. Pinar C, Degirmencioglu S, Tanrikulu Kucuk S, Seyithanoglu M, Oner Iyidogan Y, Kocak H. Association of different doses of curcumin with preadipocyte-adipocyte differentiation. Med J Bakirkoy 2024; (in press). google scholar
  • 18. Lee MS, Kim CT, Kim IH, Kim Y. Inhibitory effects of green tea catechin on the lipid accumulation in 3T3-L1 adipocytes. Phytother Res 2009; 23(8): 1088-91. google scholar
  • 19. Lee MS, Kim CT, Kim Y. Green tea (-)-epigallocatechin-3-gallate reduces body weight with regulation of multiple genes expression in adipose tissue of diet-induced obese mice. Ann Nutr Metab 2009; 54(2): 151-7. google scholar
  • 20. Inoue N, Matsunaga Y, Satoh H, Takahashi M. Enhanced energy expenditure and fat oxidation in humans with high BMI scores by the ingestion of novel and non-pungent capsaicin analogues (capsinoids). Biosci Biotechnol Biochem 2007; 71(2): 380-9. google scholar
  • 21. Zhang LL, Yan Liu D, Ma LQ, Luo ZD, Cao TB, Zhong J, et al. Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity. Circ Res 2007; 100(7): 1063-70. google scholar
  • 22. Kang SI, Kim MH, Shin HS, Kim HM, Hong YS, Park JG, et al. A water-soluble extract of Petalonia binghamiae inhibits the expression of adipogenic regulators in 3T3-L1 preadipocytes and reduces adiposity and weight gain in rats fed a high-fat diet. J Nutr Biochem 2010; 21(12): 1251-7. google scholar
  • 23. Cinti S. Transdifferentiation properties of adipocytes in the adipose organ. Am J Physiol Endocrinol Metab 2009; 297(5): E977-86. google scholar
  • 24. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM. Transcriptional regulation of adipogenesis. Genes Dev 2000; 14(11): 1293-307. google scholar
  • 25. Ibrahim M, Jang M, Park M, Gobianand K, You S, Yeon SH, et al. Capsaicin inhibits the adipogenic differentiation of bone marrow mesenchymal stem cells by regulating cell proliferation, apoptosis, oxidative and nitrosative stress. Food Funct 2015; 6(7): 2165-78. google scholar
  • 26. Lappas M, Permezel M, Rice GE. Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factor-kappaB, peroxisomal proliferator-activated receptor-gamma and extracellularly regulated kinase 1/2. Endocrinology 2005; 146(8): 3334-42. google scholar
  • 27. Cheng X, Folco EJ, Shimizu K, Libby P. Adiponectin induces pro-inflammatory programs in human macrophages and CD4+ T cells. J Biol Chem 2012; 287(44): 36896-904. google scholar
  • 28. Lira FS, Rosa JC, Pimentel GD, Seelaender M, Damaso AR, Oyama LM. Both adiponectin and interleukin-10 inhibit LPS-induced activation of the NF-kB pathway in 3T3-L1 adipocytes. Cytokine. 2012; 57(1): 98-106. google scholar
  • 29. Ajuwon KM, Spurlock ME. Adiponectin inhibits LPS-induced NF-kappaB activation and IL-6 production and increases PPARgamma2 expression in adipocytes. Am J Physiol Regul Integr Comp Physiol 2005; 288(5): R1220-5. google scholar
  • 30. Fleury C, Neverova M, Collins S, Raimbault S, Champigny O, Levi-Meyrueis C, et al. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet 1997; 15(3): 269-72. google scholar
  • 31. Rousset S, Alves-Guerra MC, Mozo J, Miroux B, Cassard-Doulcier AM, Bouillaud F, et al. The biology of mitochondrial uncoupling proteins. Diabetes 2004; 53 Suppl 1: S130-5. google scholar
  • 32. Oliveira MS, Rheinheimer J, Moehlecke M, Rodrigues M, Assmann TS, Leitâo CB, et al. CP2, IL18, and miR-133a-3p are dysregulated in subcutaneous adipose tissue of patients with obesity. Mol Cell Endocrinol 2020; 509: 110805. google scholar
  • 33. Heinitz S, Piaggi P, Yang S, Bonfiglio S, Steel J, Krakoff J, et al. Response of skeletal muscle UCP2-expression during metabolic adaptation to caloric restriction. Int J Obes (Lond) 2018; 42(5): 974-84. google scholar
  • 34. Vidal-Puig A, Rosenbaum M, Considine RC, Leibel RL, Dohm GL, Lowell BB. Effects of obesity and stable weight reduction on UCP2 and UCP3 gene expression in humans. Obes Res 1999; 7(2): 133-40. google scholar
  • 35. Lee MS, Kim CT, Kim IH, Kim Y. Effects of capsaicin on lipid catabolism in 3T3-L1 adipocytes. Phytother Res 2011; 25(6): 935-9. google scholar
  • 36. Andreyev AY, Kushnareva YE, Starkov AA. Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc) 2005; 70(2): 200-14. google scholar
  • 37. Ding Y, Zheng Y, Huang J, Peng W, Chen X, Kang X, et al. UCP2 ameliorates mitochondrial dysfunction, inflammation, and oxidative stress in lipopolysaccharide-induced acute kidney injury. Int Immunopharmacol 2019; 71: 336-49. google scholar

Citations

Copy and paste a formatted citation or use one of the options to export in your chosen format


EXPORT



APA

Değirmencioğlu, S., Çetinalp, P., Seyithanoğlu, M., Tanrıkulu Küçük, S., Koçak, H., & Öner İyidoğan, Y. (2024). Capsaicin Modulates Adipocyte Cell Differentiation and Inflammatory Gene Expression. Experimed, 14(2), 116-125. https://doi.org/10.26650/experimed.1489790


AMA

Değirmencioğlu S, Çetinalp P, Seyithanoğlu M, Tanrıkulu Küçük S, Koçak H, Öner İyidoğan Y. Capsaicin Modulates Adipocyte Cell Differentiation and Inflammatory Gene Expression. Experimed. 2024;14(2):116-125. https://doi.org/10.26650/experimed.1489790


ABNT

Değirmencioğlu, S.; Çetinalp, P.; Seyithanoğlu, M.; Tanrıkulu Küçük, S.; Koçak, H.; Öner İyidoğan, Y. Capsaicin Modulates Adipocyte Cell Differentiation and Inflammatory Gene Expression. Experimed, [Publisher Location], v. 14, n. 2, p. 116-125, 2024.


Chicago: Author-Date Style

Değirmencioğlu, Sevgin, and Pınar Çetinalp and Muhammed Seyithanoğlu and Sevda Tanrıkulu Küçük and Hikmet Koçak and Yıldız Öner İyidoğan. 2024. “Capsaicin Modulates Adipocyte Cell Differentiation and Inflammatory Gene Expression.” Experimed 14, no. 2: 116-125. https://doi.org/10.26650/experimed.1489790


Chicago: Humanities Style

Değirmencioğlu, Sevgin, and Pınar Çetinalp and Muhammed Seyithanoğlu and Sevda Tanrıkulu Küçük and Hikmet Koçak and Yıldız Öner İyidoğan. Capsaicin Modulates Adipocyte Cell Differentiation and Inflammatory Gene Expression.” Experimed 14, no. 2 (Nov. 2024): 116-125. https://doi.org/10.26650/experimed.1489790


Harvard: Australian Style

Değirmencioğlu, S & Çetinalp, P & Seyithanoğlu, M & Tanrıkulu Küçük, S & Koçak, H & Öner İyidoğan, Y 2024, 'Capsaicin Modulates Adipocyte Cell Differentiation and Inflammatory Gene Expression', Experimed, vol. 14, no. 2, pp. 116-125, viewed 15 Nov. 2024, https://doi.org/10.26650/experimed.1489790


Harvard: Author-Date Style

Değirmencioğlu, S. and Çetinalp, P. and Seyithanoğlu, M. and Tanrıkulu Küçük, S. and Koçak, H. and Öner İyidoğan, Y. (2024) ‘Capsaicin Modulates Adipocyte Cell Differentiation and Inflammatory Gene Expression’, Experimed, 14(2), pp. 116-125. https://doi.org/10.26650/experimed.1489790 (15 Nov. 2024).


MLA

Değirmencioğlu, Sevgin, and Pınar Çetinalp and Muhammed Seyithanoğlu and Sevda Tanrıkulu Küçük and Hikmet Koçak and Yıldız Öner İyidoğan. Capsaicin Modulates Adipocyte Cell Differentiation and Inflammatory Gene Expression.” Experimed, vol. 14, no. 2, 2024, pp. 116-125. [Database Container], https://doi.org/10.26650/experimed.1489790


Vancouver

Değirmencioğlu S, Çetinalp P, Seyithanoğlu M, Tanrıkulu Küçük S, Koçak H, Öner İyidoğan Y. Capsaicin Modulates Adipocyte Cell Differentiation and Inflammatory Gene Expression. Experimed [Internet]. 15 Nov. 2024 [cited 15 Nov. 2024];14(2):116-125. Available from: https://doi.org/10.26650/experimed.1489790 doi: 10.26650/experimed.1489790


ISNAD

Değirmencioğlu, Sevgin - Çetinalp, Pınar - Seyithanoğlu, Muhammed - Tanrıkulu Küçük, Sevda - Koçak, Hikmet - Öner İyidoğan, Yıldız. Capsaicin Modulates Adipocyte Cell Differentiation and Inflammatory Gene Expression”. Experimed 14/2 (Nov. 2024): 116-125. https://doi.org/10.26650/experimed.1489790



TIMELINE


Submitted25.05.2024
Accepted02.08.2024
Published Online26.08.2024

LICENCE


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


SHARE




Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.