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Suppressive Effects on Lipid Accumulation and Expression of Interleukin-1β-Mediated Inducible Nitric Oxide Synthase in 3T3-L1 Preadipocytes by a Standardized Commercial Noni Fruit Juice

Noni Fruit Juice의 3T3-L1 지방전구세포 분화 억제 및 인터루킨-1β 유도 Inducible Nitric Oxide Synthase 염증유전자 발현 감소 효과

  • Byeong-Churl Jang (Department of Molecular Medicine, Keimyung University College of Medicine)
  • 장병철 (계명대학교 의과대학 분자의학교실)
  • Received : 2023.05.05
  • Accepted : 2023.06.12
  • Published : 2023.06.30

Abstract

Objectives: Noni fruit juice (NFJ) is liquor extracted from Morinda citrifolia (noni) fruit and has been used as an herbal remedy in many countries. However, the NFJ's anti-adipogenic and anti-inflammatory effects on adipocytes are poorly understood. The purpose of this study was to explore the commercially standardized NFJ effects on lipid accumulation throughout 3T3-L1 preadipocytes differentiation and interleukin-1β (IL-1β)-mediated inducible nitric oxide synthase (iNOS) expression in 3T3-L1 preadipocytes. Methods: Cellular lipid accumulation and triglyceride (TG) content in differentiating 3T3-L1 preadipocytes were assessed subsequently via the Oil Red O staining and AdipoRed assay. MTS assay was used to examine NFJ cytotoxicity in (differentiating) 3T3-L1 preadipocytes. Immunoblotting and reverse transcriptase polymerase chain reaction analysis were used to measure the expression levels of target protein and mRNA in (differentiating) 3T3-L1 preadipocytes, respectively. Results: NFJ treatment at 150 μL/mL led to a substantial reduction of fat accumulation and TG content during 3T3-L1 adipogenesis with no discernable impact on the cell viability. Of note, while NFJ treatment (150 μL/mL) largely inhibited the CCAAT/enhancer-binding protein-α (C/EBP-α) and peroxisome proliferator-activated receptor-β (PPAR-β) protein expressions, it did not influence PPAR-γ in differentiating 3T3-L1 preadipocytes. Of interest, treatment with IL-1β at 20 ng/mL for 4 hours elicited in firm induction of iNOS mRNA expression in 3T3-L1 preadipocytes. However, NFJ treatment at 100 or 200 μL/mL greatly attenuated the IL-1β-induced iNOS mRNA expression in 3T3-L1 preadipocytes. Conclusions: NFJ has anti-adipogenic and anti-inflammatory effects on (differentiating) 3T3-L1 preadipocytes which are in part intervened via control of the expression of C/EBP-α, PPAR-β, and iNOS.

Keywords

References

  1. Boutari C, Mantzoros CS. A 2022 update on the epidemiology of obesity and a call to action: as its twin COVID-19 pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on. Metabolism. 2022 ; 133 : 155217.
  2. Phelan SM, Burgess DJ, Yeazel MW, Hellerstedt WL, Griffin JM, van Ryn M. Impact of weight bias and stigma on quality of care and outcomes for patients with obesity. Obes Rev. 2015 ; 16(4) : 319-26. https://doi.org/10.1111/obr.12266
  3. Longo M, Zatterale F, Naderi J, Parrillo L, Formisano P, Raciti GA, et al. Adipose tissue dysfunction as determinant of obesity-associated metabolic complications. Int J Mol Sci. 2019 ; 20(9) : 2358.
  4. Liu F, He J, Wang H, Zhu D, Bi Y. Adipose morphology: a critical factor in regulation of human metabolic diseases and adipose tissue dysfunction. Obes Surg. 2020 ; 30(12) : 5086-100. https://doi.org/10.1007/s11695-020-04983-6
  5. Reyes-Farias M, Fos-Domenech J, Serra D, Herrero L, Sanchez-Infantes D. White adipose tissue dysfunction in obesity and aging. Biochem Pharmacol. 2021 ; 192 : 114723.
  6. Ali AT, Hochfeld WE, Myburgh R, Pepper MS. Adipocyte and adipogenesis. Eur J Cell Biol. 2013 ; 92(6-7) : 229-36. https://doi.org/10.1016/j.ejcb.2013.06.001
  7. Jakab J, Miskic B, Miksic S, Juranic B, Cosic V, Schwarz D, et al. Adipogenesis as a potential anti-obesity target: a review of pharmacological treatment and natural products. Diabetes Metab Syndr Obes. 2021 ; 14 : 67-83. https://doi.org/10.2147/DMSO.S281186
  8. Tang P, Virtue S, Goie JYG, Png CW, Guo J, Li Y, et al. Regulation of adipogenic differentiation and adipose tissue inflammation by interferon regulatory factor 3. Cell Death Differ. 2021 ; 28 : 3022-35. https://doi.org/10.1038/s41418-021-00798-9
  9. Farmer SR. Transcriptional control of adipocyte formation. Cell Metab. 2006 ; 4( 4) : 263-73. https://doi.org/10.1016/j.cmet.2006.07.001
  10. Bahmad HF, Daouk R, Azar J, Sapudom J, Teo JCM, Abou-Kheir W, et al. Modeling adipogenesis: current and future perspective. Cells. 2020 ; 9(10) : 2326.
  11. Matsusue K, Peters JM, Gonzalez FJ. PPARβ/δ potentiates PPARγ-stimulated adipocyte differentiation. FASEB J. 2004 ; 18(12) : 1477-9. https://doi.org/10.1096/fj.04-1944fje
  12. Sarjeant K, Stephens JM. Adipogenesis. Cold Spring Harb Perspect Biol. 2012 ; 4( 9) : a008417.
  13. Becerril S, Rodriguez A, Catalan V, Mendez-Gimenez L, Ramirez B, Sainz N, et al. Targeted disruption of the iNOS gene improves adipose tissue inflammation and fibrosis in leptin-deficient ob/ob mice: role of tenascin C. Int J Obes (Lond). 2018 ; 42 : 1458-70. https://doi.org/10.1038/s41366-018-0005-5
  14. Noronha BT, Li JM, Wheatcroft SB, Shah AM, Kearney MT. Inducible nitric oxide synthase has divergent effects on vascular and metabolic function in obesity. Diabetes. 2005 ; 54(4) : 1082-9. https://doi.org/10.2337/diabetes.54.4.1082
  15. Dallaire P, Bellmann K, Laplante M, Gelinas S, CentenoBaez C, Penfornis P, et al. Obese mice lacking inducible nitric oxide synthase are sensitized to the metabolic actions of peroxisome proliferator-activated receptor-γ agonism. Diabetes. 2008 ; 57(8) : 1999-2011. https://doi.org/10.2337/db08-0540
  16. Samoylenko V, Zhao J, Dunbar DC, Khan IA, Rushing JW, Muhammad I. New constituents from noni (Morinda citrifolia) fruit juice. J Agric Food Chem. 2006 ; 54(17) : 6398-402. https://doi.org/10.1021/jf060672u
  17. Chan-Blanco Y, Vaillant F, Mercedes Perez A, Reynes M, Brillouet JM, Brat P. The noni fruit (Morinda citrifolia L.): a review of agricultural research, nutritional and therapeutic properties. J Food Comp Anal. 2006 ; 19(6-7) : 645-54. https://doi.org/10.1016/j.jfca.2005.10.001
  18. Zhang WM, Wang W, Zhang JJ, Wang ZR, Wang Y, Hao WJ, et al. Antibacterial constituents of Hainan Morinda Citrifolia (Noni) leaves. J Food Sci. 2016 ; 81(5) : M1192-6. https://doi.org/10.1111/1750-3841.13302
  19. Huang HL, Ko CH, Yan YY, Wang CK. Antiadhesion and anti-inflammation effects of Noni (Morinda citrifolia) fruit extracts on AGS cells during Helicobacter pylori infection. J Agric Food Chem. 2014 ; 62(11) : 2374-83. https://doi.org/10.1021/jf405199w
  20. Palu AK, Seifulla RD, West BJ. Morinda citrifolia L. (noni) improves athlete endurance: its mechanisms of action. J Med Plant Res. 2008 ; 2(7) : 154-8.
  21. Lin YL, Chang YY, Yang DJ, Tzang BS, Chen YC. Beneficial effects of noni ( Morinda citrifolia L.) juice on livers of high-fat dietary hamsters. Food Chem. 2013 ; 140(1-2) : 31-8. https://doi.org/10.1016/j.foodchem.2013.02.035
  22. Lin YL, Chou CH, Yang DJ, Chen JW, Tzang BS, Chen YC. Hypolipidemic and antioxidative effects of noni (Morinda citrifolia L.) juice on high- fat/cholesterol-dietary hamsters. Plant Foods Hum Nutr. 2012 ; 67(3) : 294-302. https://doi.org/10.1007/s11130-012-0309-x
  23. Nerurkar PV, Nishioka A, Eck PO, Johns LM, Volper E, Nerurkar VR. Regulation of glucose metabolism via hepatic forkhead transcription factor 1 (FOXO1) by Morinda citrifolia (noni) in high-fat diet-induced obese mice. Br J Nutr. 2012 ; 108(2) : 218-28. https://doi.org/10.1017/S0007114511005563
  24. Jang BC. The fruit juice of Morinda citrifolia (noni) downregulates HIF-1α protein expression through inhibition of PKB, ERK-1/2, JNK-1 and S6 in manganese-stimulated A549 human lung cancer cells. Int J Mol Med. 2012 ; 29( 3) : 499-504. https://doi.org/10.3892/ijmm.2011.860
  25. McGillicuddy FC, Chiquoine EH, Hinkle CC, Kim RJ, Shah R, Roche HM, et al. Interferon γ attenuates insulin signaling, lipid storage, and differentiation in human adipocytes via activation of the JAK/STAT pathway. J Biol Chem. 2009 ; 284(46) : 31936-44. https://doi.org/10.1074/jbc.M109.061655
  26. Ellulu MS, Patimah I, Khaza'ai H, Rahmat A, Abed Y. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci. 2017 ; 13(4) : 851-63. https://doi.org/10.5114/aoms.2016.58928
  27. Palu AK, Kim AH, West BJ, Deng S, Jensen J, White L. The effects of Morinda citrifolia L. (noni) on the immune system: its molecular mechanisms of action. J Ethnopharmacol. 2007 ; 115(3) : 502-6. https://doi.org/10.1016/j.jep.2007.10.023
  28. Kang JH, Song KB. Antibacterial activity of the noni fruit extract against Listeria monocytogenes and its applicability as a natural sanitizer for the washing of fresh-cut produce. Food Microbiol. 2019 ; 84 : 103260.
  29. Ida SR, Rodolfo QC, Jorge RA, Irving XR, Luicita LR, Isaac AM, et al. Beneficial effects of Morinda Citrifolia Linn. (noni) leaf extract on obesity, dyslipidemia and adiponectinemia in rats with metabolic syndrome. Int J Pharm Sci Res. 2017 ; 8(2) : 2496-503.
  30. Motshakeri M, Ghazali HM. Nutritional, phytochemical and commercial quality of noni fruit: a multi-beneficial gift from nature. Trends Food Sci Technol. 2015 ; 45(1) : 118-29. https://doi.org/10.1016/j.tifs.2015.06.004
  31. Ong KW, Hsu A, Tan BK. Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by AMPK activation. Biochem Pharmacol. 2013 ; 85(9) : 1341-51. https://doi.org/10.1016/j.bcp.2013.02.008
  32. Cao Z, Umek RM, McKnight SL. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 1991 ; 5(9) : 1538-52. https://doi.org/10.1101/gad.5.9.1538
  33. Ma X, Wang D, Zhao W, Xu L. Deciphering the roles of PPARγ in adipocytes via dynamic change of transcription complex. Front Endocrinol. 2018 ; 9 : 473.
  34. Lee JE, Schmidt H, Lai B, Ge K. Transcriptional and epigenomic regulation of adipogenesis. Mol Cell Biol. 2019 ; 39(11) : e00601-18. https://doi.org/10.1128/MCB.00601-18
  35. de Sa PM, Richard AJ, Hardy H, Stephens JM. Transcriptional regulation of adipogenesis. Compr Physiol. 2017 ; 7( 2) : 635-74. https://doi.org/10.1002/cphy.c160022
  36. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM. Transcriptional regulation of adipogenesis. Genes Dev. 2000 ; 14(11) : 1293-307. https://doi.org/10.1101/gad.14.11.1293
  37. Li H, Kang JH, Han JM, Cho MH, Chung YJ, Park KH, et al. Anti-obesity effects of soy leaf via regulation of adipogenic transcription factors and fat oxidation in diet-induced obese mice and 3T3-L1 adipocytes. J Med Food. 2015 ; 18( 8) : 899-908. https://doi.org/10.1089/jmf.2014.3388
  38. Lin YL, Chang YY, Yang DJ, Tzang BS, Chen YC. Beneficial effects of noni (Morinda citrifolia L.) juice on livers of high-fat dietary hamsters. Food Chem. 2013 ; 140(1-2) : 31-8. https://doi.org/10.1016/j.foodchem.2013.02.035
  39. Liu JL, Zhang R, Liu YB, Hou Y, Wang LY, Wang C, et al. Literature research and discussion of Chinese medicinal properties of Morinda citrifolia. Zhongguo Zhong Yao Za Zhi. 2020 ; 45(5) : 984-90.
  40. Nerurkar PV, Hwang PW, Saksa E. Anti-diabetic potential of noni: the yin and the yang. Molecules. 2015 ; 20( 10) : 17684-719. https://doi.org/10.3390/molecules201017684