DOI QR코드

DOI QR Code

Anti-Obesity Effect of Lactobacillus acidophilus DS0079 (YBS1) by Inhibition of Adipocyte Differentiation through Regulation of p38 MAPK/PPARγ Signaling

  • Youri Lee (Department of Microbiology, College of Medicine, Soonchunhyang University) ;
  • Navid Iqbal (Department of Microbiology, College of Medicine, Soonchunhyang University) ;
  • Mi-Hwa Lee (Nakdonggang National Institute of Biological Resources) ;
  • Doo-Sang Park (Biological Resource Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Yong-Sik Kim (Department of Microbiology, College of Medicine, Soonchunhyang University)
  • Received : 2024.02.07
  • Accepted : 2024.03.18
  • Published : 2024.05.28

Abstract

Obesity is spawned by an inequality between the portion of energy consumed and the quantity of energy expended. Disease entities such as cardiovascular disease, arteriosclerosis, hypertension, and cancer, which are correlated with obesity, influence society and the economy. Suppression of adipogenesis, the process of white adipocyte generation, remains a promising approach for treating obesity. Oil Red O staining was used to differentiate 3T3-L1 cells for screening 20 distinct Lactobacillus species. Among these, Lactobacillus acidophilus DS0079, referred to as YBS1, was selected for further study. YBS1 therapy decreased 3T3-L1 cell development. Triglyceride accumulation and mRNA expression of the primary adipogenic marker, peroxisome proliferator-activated receptor gamma (PPARγ), including its downstream target genes, adipocyte fatty acid binding protein 4 and adiponectin, were almost eliminated. YBS1 inhibited adipocyte differentiation at the early stage (days 0-2), but no significant difference was noted between the mid-stage (days 2-4) and late-stage (days 4-6) development. YBS1 stimulated the activation of p38 mitogen-activated protein kinase (p38 MAPK) during the early stages of adipogenesis; however, this effect was eliminated by the SB203580 inhibitor. The data showed that YBS1 administration inhibited the initial development of adipocytes via stimulation of the p38 MAPK signaling pathway, which in turn controlled PPARγ expression. In summary, YBS1 has potential efficacy as an anti-obesity supplement and requires further exploration.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2015R1A6A103032522) and by the Korea Environmental Industry & Technology Institute (KEITI) through the Project to Make Multi-Ministerial National Biological Research Resources More Advanced funded by Korea Ministry of Environment (MOE) (2021003420003). This research was supported partially by a research fund of the Soonchunhyang University.

References

  1. Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, et al. 2017. Health effects of overweight and obesity in 195 countries over 25 years. N. Engl. J. Med. 377: 13-27. https://doi.org/10.1056/NEJMoa1614362
  2. Charakida M, Khan T, Johnson W, Finer N, Woodside J, Whincup PH, et al. 2014. Lifelong patterns of BMI and cardiovascular phenotype in individuals aged 60-64 years in the 1946 British birth cohort study: an epidemiological study. Lancet Diab. Endocrinol. 2: 648-654. https://doi.org/10.1016/S2213-8587(14)70103-2
  3. Thaker VV. 2017. Genetic and epigenetic causes of obesity. Adolesc. Med. State Art Rev. 28: 379-405. https://doi.org/10.1542/9781581109405-genetic
  4. Sheykhsaran E, Abbasi A, Ebrahimzadeh Leylabadlo H, Sadeghi J, Mehri S, Naeimi Mazraeh F, et al. 2022. Gut microbiota and obesity: an overview of microbiota to microbial-based therapies. Postgrad. Med. J. 99: 384-402. https://doi.org/10.1136/postgradmedj-2021-141311
  5. Muller TD, Bluher M, Tschop MH, DiMarchi RD. 2022. Anti-obesity drug discovery: advances and challenges. Nat. Rev. Drug Discov. 21: 201-223. https://doi.org/10.1038/s41573-021-00337-8
  6. Lin X, Li H. 2021. Obesity: epidemiology, pathophysiology, and therapeutics. Front. Endocrinol (Lausanne) 12: 706978.
  7. Ahirwar R, Mondal PR. 2019. Prevalence of obesity in India: a systematic review. Diabetes Metab. Syndr. 13: 318-321. https://doi.org/10.1016/j.dsx.2018.08.032
  8. Collaboration NRF. 2016. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet 387: 1377-1396. https://doi.org/10.1016/S0140-6736(16)30054-X
  9. Audano M, Pedretti S, Caruso D, Crestani M, De Fabiani E, Mitro N. 2022. Regulatory mechanisms of the early phase of white adipocyte differentiation: an overview. Cell Mol. Life Sci. 79: 139.
  10. Du Y, Li DX, Lu DY, Zhang R, Zhong QQ, Zhao YL, et al. 2022. Amelioration of lipid accumulations and metabolism disorders in differentiation and development of 3T3-L1 adipocytes through mulberry leaf water extract. Phytomedicine 98: 153959.
  11. Ghaben AL, Scherer PE. 2019. Adipogenesis and metabolic health. Nat. Rev. Mol. Cell. Biol. 20: 242-258. https://doi.org/10.1038/s41580-018-0093-z
  12. Matias-Perez D, Hernandez-Bautista E, Garcia-Montalvo IA. 2022. Intermittent fasting may optimize intestinal microbiota, adipocyte status and metabolic health. Asia Pac. J. Clin. Nutr. 31: 16-23.
  13. Gonzalez-Casanova JE, Pertuz-Cruz SL, Caicedo-Ortega NH, Rojas-Gomez DM. 2020. Adipogenesis regulation and endocrine disruptors: emerging insights in obesity. Biomed Res. Int. 2020: 7453786.
  14. Wu R, Feng S, Li F, Shu G, Wang L, Gao P, et al. 2023. Transcriptional and post-transcriptional control of autophagy and adipogenesis by YBX1. Cell Death Dis. 14: 29.
  15. Jakab J, Miskic B, Miksic S, Juranic B, Cosic V, Schwarz D, et al. 2021. Adipogenesis as a potential anti-obesity target: a review of pharmacological treatment and natural products. Diabetes Metab. Syndr. Obes. 14: 67-83. https://doi.org/10.2147/DMSO.S281186
  16. Cheng HL, Chang WT, Lin JL, Cheng MC, Huang SC, Chen SC, et al. 2023. An innovative mei-gin formula exerts anti-adipogenic and anti-obesity effects in 3T3-L1 adipocyte and high-fat diet-induced obese rats. Foods 12: 945.
  17. Ahmad B, Serpell CJ, Fong IL, Wong EH. 2020. Molecular mechanisms of adipogenesis: the anti-adipogenic role of AMP-activated protein kinase. Front. Mol. Biosci. 7: 76.
  18. Christodoulides C, Lagathu C, Sethi JK, Vidal-Puig A. 2009. Adipogenesis and WNT signalling. Trends Endocrinol. Metab. 20: 16-24. https://doi.org/10.1016/j.tem.2008.09.002
  19. Oh JH, Karadeniz F, Lee JI, Seo Y, Kong CS. 2019. Artemisia princeps inhibits adipogenic differentiation of 3T3-L1 pre-adipocytes via downregulation of PPARγ and MAPK pathways. Prev. Nutr. Food Sci. 24: 299-307. https://doi.org/10.3746/pnf.2019.24.3.299
  20. Sadeghi A, Ebrahimi M, Kharazmi MS, Jafari SM. 2023. Effects of microbial-derived biotics (meta/pharma/post-biotics) on the modulation of gut microbiome and metabolome; general aspects and emerging trends. Food Chem. 411: 135478.
  21. Hossain M, Park DS, Rahman M, Ki SJ, Lee YR, Imran K, et al. 2020. Bifidobacterium longum DS0956 and Lactobacillus rhamnosus DS0508 culture-supernatant ameliorate obesity by inducing thermogenesis in obese-mice. Benef. Microbes 11: 361-373. https://doi.org/10.3920/BM2019.0179
  22. Ayivi RD, Gyawali R, Krastanov A, Aljaloud SO, Worku M, Tahergorabi R, et al. 2020. Lactic acid bacteria: food safety and human health applications. Dairy 1: 202-232. https://doi.org/10.3390/dairy1030015
  23. Chalas R, Janczarek M, Bachanek T, Mazur E, Cieszko-Buk M, Szymanska J. 2016. Characteristics of oral probiotics-a review. Curr. Issues Pharm. Med. Sci. 29: 8-10. https://doi.org/10.1515/cipms-2016-0002
  24. Sung V, D'Amico F, Cabana MD, Chau K, Koren G, Savino F, et al. 2018. Lactobacillus reuteri to treat infant colic: a meta-analysis. Pediatrics 141: e20171811.
  25. Oh S. 2019. Lactobacillus acidophilus as a probiotics. J. Dairy Sci. Biotechnol. 37: 155-166. https://doi.org/10.22424/jmsb.2019.37.3.155
  26. Hossain M, Park DS, Rahman MS, Ki SJ, Lee YR, Imran KM, et al. 2020. Bifidobacterium longum DS0956 and Lactobacillus rhamnosus DS0508 culture-supernatant ameliorate obesity by inducing thermogenesis in obese-mice. Benef. Microbes 11: 361-373. https://doi.org/10.3920/BM2019.0179
  27. Aouadi M, Laurent K, Prot M, Le Marchand-Brustel Y, Binetruy B, Bost F. 2006. Inhibition of p38MAPK increases adipogenesis from embryonic to adult stages. Diabetes 55: 281-289. https://doi.org/10.2337/diabetes.55.02.06.db05-0963
  28. Ejtahed HS, Angoorani P, Soroush AR, Atlasi R, Hasani-Ranjbar S, Mortazavian AM, et al. 2019. Probiotics supplementation for the obesity management; A systematic review of animal studies and clinical trials. J. Funct. Foods 52: 228-242. https://doi.org/10.1016/j.jff.2018.10.039
  29. Jeong Y, Kim H, Lee JY, Won G, Choi SI, Kim GH, et al. 2021. The antioxidant, anti-diabetic, and anti-adipogenesis potential and probiotic properties of lactic acid bacteria isolated from human and fermented foods. Fermentation 7: 123.
  30. Cho Y, Shamim RM, Kim YS. 2019. Obesity regulation through gut microbiota modulation and adipose tissue browning. J. Life Sci. 29: 922-940.
  31. Park DY, Ahn YT, Huh CS, Jeon SM, Choi MS. 2011. The inhibitory effect of Lactobacillus plantarum KY1032 cell extract on the adipogenesis of 3T3-L1 cells. J. Med. Food 14: 670-675. https://doi.org/10.1089/jmf.2010.1355
  32. Kim S, Huang E, Park S, Holzapfel W, Lim SD. 2018. Physiological characteristics and anti-obesity effect of Lactobacillus plantarum K10. Korean J. Food Sci. Anim. Resour. 38: 554.
  33. Kang JH, Yun SI, Park HO. 2010. Effects of Lactobacillus gasseri BNR17 on body weight and adipose tissue mass in diet-induced overweight rats. J. Microbiol. 48: 712-714. https://doi.org/10.1007/s12275-010-0363-8
  34. Naito E, Yoshida Y, Makino K, Kounoshi Y, Kunihiro S, Takahashi R, et al. 2011. Beneficial effect of oral administration of Lactobacillus casei strain shirota on insulin resistance in diet-induced obesity mice. J. Appl. Microbiol. 110: 650-657. https://doi.org/10.1111/j.1365-2672.2010.04922.x
  35. Farmer SR. 2006. Transcriptional control of adipocyte formation. Cell Metab. 4: 263-273. https://doi.org/10.1016/j.cmet.2006.07.001
  36. Rosen ED, MacDougald OA. 2006. Adipocyte differentiation from the inside out. Nat. Rev. Mol. Cell Biol. 7: 885-896. https://doi.org/10.1038/nrm2066
  37. Tontonoz P, Hu E, Spiegelman BM. 1994. Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor. Cell 79: 1147-1156. https://doi.org/10.1016/0092-8674(94)90006-X
  38. Rungsa P, San HT, Sritularak B, Bottcher C, Prompetchara E, Chaotham C, et al. 2023. Inhibitory effect of isopanduratin A on adipogenesis: a study of possible mechanisms. Foods 12: 1014.
  39. Lee MH, Kim HM, Chung HC, Lee JH. 2020. Licorice extract suppresses adipogenesis through regulation of mitotic clonal expansion and adenosine monophosphate-activated protein kinase in 3T3-L1 cells. J. Food Biochem. 44: e13528.
  40. Gong Z, Han S, Li C, Meng T, Huo Y, Liu X, et al. 2023. Rhinacanthin C Ameliorates insulin resistance and lipid accumulation in NAFLD mice via the AMPK/SIRT1 and SREBP-1c/FAS/ACC signaling pathways. Evid. Based Complement. Alternat. Med. 2023: 6603522.
  41. Yang M, Zheng J, Zong X, Yang X, Zhang Y, Man C, et al. 2021. Preventive effect and molecular mechanism of Lactobacillus rhamnosus JL1 on food-borne obesity in mice. Nutrients 13: 3989.
  42. Soundharrajan I, Kuppusamy P, Srisesharam S, Lee JC, Sivanesan R, Kim D, et al. 2020. Positive metabolic effects of selected probiotic bacteria on diet-induced obesity in mice are associated with improvement of dysbiotic gut microbiota. FASEB J. 34: 12289-12307. https://doi.org/10.1096/fj.202000971R
  43. Rahman MS, Kang I, Lee Y, Habib MA, Choi BJ, Kang JS, et al. 2021. Bifidobacterium longum subsp. infantis YB0411 inhibits adipogenesis in 3T3-L1 pre-adipocytes and reduces high-fat-diet-induced obesity in mice. J. Agric. Food Chem. 69: 6032-6042. https://doi.org/10.1021/acs.jafc.1c01440
  44. Lee J, Park S, Oh N, Park J, Kwon M, Seo J, et al. 2021. Oral intake of Lactobacillus plantarum L-14 extract alleviates TLR2-and AMPK-mediated obesity-associated disorders in high-fat-diet-induced obese C57BL/6J mice. Cell Prolif. 54: e13039.
  45. Althaher AR. 2022. An Overview of Hormone-Sensitive Lipase (HSL). ScientificWorldJournal 2022: 1964684.
  46. Kim S, Choi SI, Jang M, Jeong Y, Kang CH, Kim GH. 2020. Anti-adipogenic effect of Lactobacillus fermentum MG4231 and MG4244 through AMPK pathway in 3T3-L1 preadipocytes. Food Sci. Biotechnol. 29: 1541-1551. https://doi.org/10.1007/s10068-020-00819-2
  47. Cheng L, Wang J, Dai H, Duan Y, An Y, Shi L, et al. 2021. Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus. Adipocyte 10: 48-65. https://doi.org/10.1080/21623945.2020.1870060
  48. Kurylowicz A, Puzianowska-Kuznicka M. 2020. Induction of adipose tissue browning as a strategy to combat obesity. Int. J. Mol. Sci. 21: 6241.
  49. Park SS, Lee YJ, Kang H, Yang G, Hong EJ, Lim JY, et al. 2019. Lactobacillus amylovorus KU4 ameliorates diet-induced obesity in mice by promoting adipose browning through PPARγ signaling. Sci. Rep. 9: 20152.
  50. Kang Y, Kang X, Yang H, Liu H, Yang X, Liu Q, et al. 2022. Lactobacillus acidophilus ameliorates obesity in mice through modulation of gut microbiota dysbiosis and intestinal permeability. Pharmacol. Res. 175: 106020.