DOI QR코드

DOI QR Code

Bifidobacterium bifidum DS0908 and Bifidobacterium longum DS0950 Culture-Supernatants Ameliorate Obesity-Related Characteristics in Mice with High-Fat Diet-Induced Obesity

  • M. Shamim Rahman (Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University) ;
  • Youri Lee (Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University) ;
  • Doo-Sang Park (Biological Resource Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Yong-Sik Kim (Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University)
  • Received : 2022.10.26
  • Accepted : 2022.11.14
  • Published : 2023.01.28

Abstract

Probiotic supplements have promising therapeutic effects on chronic diseases. In this study, we demonstrated the anti-obesity effects of two potential probiotics, Bifidobacterium bifidum DS0908 (DS0908) and Bifidobacterium longum DS0950 (DS0950). Treatment with DS0908 and DS0950 postbiotics significantly induced the expression of the brown adipocyte-specific markers UCP1, PPARγ, PGC1α, PRDM16 and beige adipocyte-specific markers CD137, FGF21, P2RX5, and COX2 in C3H10T1/2 mesenchymal stem cells (MSCs). In mice with high-fat diet (HFD)-induced obesity, both potential probiotics and postbiotics noticeably reduced body weight and epididymal fat accumulation without affecting food intake. DS0908 and DS0950 also improved insulin sensitivity and glucose use in mice with HFD-induced obesity. In addition, DS0908 and DS0950 improved the plasma lipid profile, proved by reduced triglyceride, low-density lipoprotein, and cholesterol levels. Furthermore, DS0908 and DS0950 improved mitochondrial respiratory function, confirmed by the high expression of oxidative phosphorylation proteins, during thermogenesis induction in the visceral and epididymal fat in mice with HFD-induced obesity. Notably, the physiological and metabolic changes were more significant after treatment with potential probiotic culture-supernatants than those with the bacterial pellet. Finally, gene knockdown and co-treatment with inhibitor-mediated mechanistic analyses showed that both DS0908 and DS0950 exerted anti-obesity-related effects via the PKA/p38 MAPK signaling activation in C3H10T1/2 MSCs. Our observations suggest that DS0908 and DS0950 could potentially alleviate obesity as dietary supplements.

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; 2016M3A9A5919255) and partially by a research fund of Soonchunhyang University.

References

  1. Yoo JY, Kim SS. 2016. Probiotics and prebiotics: Present status and future perspectives on metabolic disorders. Nutrients 8: 173-173. https://doi.org/10.3390/nu8030173
  2. George Kerry R, Patra JK, Gouda S, Park Y, Shin H-S, Das G. 2018. Benefaction of probiotics for human health: a review. J. Food Drug Anal. 26: 927-939. https://doi.org/10.1016/j.jfda.2018.01.002
  3. Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi SJ, et al. 2019. Prebiotics: definition, types, sources, mechanisms, and clinical applications. Foods 8: 92.
  4. Markowiak P, Slizewska K. 2017. Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients 9: 1021.
  5. Sugahara H, Odamaki T, Fukuda S, Kato T, Xiao J-z, Abe F, et al. 2015. Probiotic Bifidobacterium longum alters gut luminal metabolism through modification of the gut microbial community. Sci. Rep. 5: 13548.
  6. Reynes B, Palou M, Rodriguez AM, Palou A. 2019. Regulation of adaptive thermogenesis and browning by prebiotics and postbiotics. Front. Physiol. 9: 1908.
  7. 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
  8. 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
  9. Hu J, Kyrou I, Tan BK, Dimitriadis GK, Ramanjaneya M, Tripathi G, et al. 2016. Short-chain fatty acid acetate stimulates adipogenesis and mitochondrial biogenesis via GPR43 in brown adipocytes. Endocrinology 157: 1881-1894. https://doi.org/10.1210/en.2015-1944
  10. Haynes VR, Michael NJ, van den Top M, Zhao FY, Brown RD, De Souza D, et al. 2020. A neural basis for octanoic acid regulation of energy balance. Mol. Metab. 34: 54-71. https://doi.org/10.1016/j.molmet.2020.01.002
  11. Cho Y, Shamim Rahman M, Kim Y-S. 2019. Obesity regulation through gut microbiota modulation and adipose tissue browning. J. Life Sci. 29: 922-940.
  12. Chichlowski M, Shah N, Wampler JL, Wu SS, Vanderhoof JA. 2020. Bifidobacterium longum subspecies infantis (B. infantis) in pediatric nutrition: current state of knowledge. Nutrients 12: 1581.
  13. Christian M. 2020. Elucidation of the roles of brown and brite fat genes: GPR120 is a modulator of brown adipose tissue function. Exp. Physiol. 105: 1201-1205. https://doi.org/10.1113/EP087877
  14. Cypess AM, Kahn CR. 2010. Brown fat as a therapy for obesity and diabetes. Curr. Opin. Endocrinol. Diabetes Obes. 17: 143-149. https://doi.org/10.1097/MED.0b013e328337a81f
  15. Zwick RK, Guerrero-Juarez CF, Horsley V, Plikus MV. 2018. Anatomical, physiological, and functional diversity of adipose tissue. Cell Metab. 27: 68-83. https://doi.org/10.1016/j.cmet.2017.12.002
  16. Longo M, Zatterale F, Naderi J, Parrillo L, Formisano P, Raciti GA, et al. 2019. Adipose tissue dysfunction as determinant of obesity-associated metabolic complications. Int. J. Mol. Sci. 20: 2358.
  17. Ouchi N, Parker JL, Lugus JJ, Walsh K. 2011. Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol. 11: 85-97. https://doi.org/10.1038/nri2921
  18. Rosenwald M, Wolfrum C. 2014. The origin and definition of brite versus white and classical brown adipocytes. Adipocyte 3: 4-9. https://doi.org/10.4161/adip.26232
  19. Hossain M, Imran KM, Rahman MS, Yoon D, Marimuthu V, Kim YS. 2020. Sinapic acid induces the expression of thermogenic signature genes and lipolysis through activation of PKA/CREB signaling in brown adipocytes. BMB Rep. 53: 142-147. https://doi.org/10.5483/BMBRep.2020.53.3.093
  20. Loft A, Forss I, Siersbaek MS, Schmidt SF, Larsen A-SB, Madsen JGS, et al. 2015. Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers. Genes Dev. 29: 7-22. https://doi.org/10.1101/gad.250829.114
  21. Rahman MS, Imran KM, Hossain M, Lee T-J, Kim Y-S. 2021. Biochanin A induces a brown-fat phenotype via improvement of mitochondrial biogenesis and activation of AMPK signaling in murine C3H10T1/2 mesenchymal stem cells. Phytother. Res. 35: 920-931. https://doi.org/10.1002/ptr.6845
  22. Imran KM, Rahman N, Yoon D, Jeon M, Lee B-T, Kim Y-S. 2017. Cryptotanshinone promotes commitment to the brown adipocyte lineage and mitochondrial biogenesis in C3H10T1/2 mesenchymal stem cells via AMPK and p38-MAPK signaling. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1862: 1110-1120. https://doi.org/10.1016/j.bbalip.2017.08.001
  23. Tzameli I, Fang H, Ollero M, Shi H, Hamm JK, Kievit P, et al. 2004. Regulated production of a peroxisome proliferator-activated receptor-γ ligand during an early phase of adipocyte differentiation in 3T3-L1 adipocytes. J. Biol. Chem. 279: 36093-36102. https://doi.org/10.1074/jbc.M405346200
  24. Becerril S, Gomez-Ambrosi J, Martin M, Moncada R, Sesma P, Burrell MA, et al. 2013. Role of PRDM16 in the activation of brown fat programming. Relevance to the development of obesity. Histol. Histopathol. 28: 1411-1425.
  25. Wang W, Ishibashi J, Trefely S, Shao M, Cowan AJ, Sakers A, et al. 2019. A PRDM16-driven metabolic signal from adipocytes regulates precursor cell fate. Cell Metab. 30: 174-189.e175. https://doi.org/10.1016/j.cmet.2019.05.005
  26. Ishibashi J, Seale P. 2015. Functions of Prdm16 in thermogenic fat cells. Temperature (Austin) 2: 65-72. https://doi.org/10.4161/23328940.2014.974444
  27. Ventura-Clapier R, Garnier A, Veksler V. 2008. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1α. Cardiovasc. Res. 79: 208-217. https://doi.org/10.1093/cvr/cvn098
  28. Cheng C-F, Ku H-C, Lin H. 2018. PGC-1α as a pivotal factor in lipid and metabolic regulation. Int. J. Mol. Sci. 19: 3447.
  29. Smith RAJ, Hartley RC, Cocheme HM, Murphy MP. 2012. Mitochondrial pharmacology. Trends Pharmacol. Sci. 33: 341-352. https://doi.org/10.1016/j.tips.2012.03.010
  30. Coleman OI, Haller D. 2017. Bacterial signaling at the intestinal epithelial interface in inflammation and cancer. Front. Immunol. 8: 1927.
  31. Mishra A, Lai GC, Yao LJ, Aung TT, Shental N, Rotter-Maskowitz A, et al. 2021. Microbial exposure during early human development primes fetal immune cells. Cell 184: 3394-3409.e3320. https://doi.org/10.1016/j.cell.2021.04.039
  32. Kim JS, Choe H, Kim KM, Lee YR, Rhee MS, Park DS. 2018. Lactobacillus porci sp. nov., isolated from small intestine of a swine. Int. J. Syst. Evol. Microbiol. 68: 3118-3124. https://doi.org/10.1099/ijsem.0.002949
  33. Prasad J, Gill H, Smart J, Gopal PK. 1998. Selection and characterisation of Lactobacillus and Bifidobacterium strains for use as probiotics. Int. Dairy J. 8: 993-1002. https://doi.org/10.1016/S0958-6946(99)00024-2
  34. Heymsfield SB, Wadden TA. 2017. Mechanisms, pathophysiology, and management of obesity. New Eng. J. Med. 376: 254-266. https://doi.org/10.1056/NEJMra1514009
  35. Petrakis D, Margina D, Tsarouhas K, Tekos F, Stan M, Nikitovic D, et al. 2020. Obesity - a risk factor for increased COVID-19 prevalence, severity and lethality (Review). Mol. Med. Rep. 22: 9-19. https://doi.org/10.3892/mmr.2020.11127
  36. Vallianou N, Stratigou T, Christodoulatos GS, Tsigalou C, Dalamaga M. 2020. Probiotics, prebiotics, synbiotics, postbiotics, and obesity: current evidence, controversies, and perspectives. Curr. Obes. Rep. 9: 179-192. https://doi.org/10.1007/s13679-020-00379-w
  37. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM. 2000. Transcriptional regulation of adipogenesis. Genes Dev. 14: 1293-1307. https://doi.org/10.1101/gad.14.11.1293
  38. Mota de Sa P, Richard AJ, Hang H, Stephens JM. 2017. Transcriptional regulation of adipogenesis. Comp. Physiol. 7: 635-674. https://doi.org/10.1002/cphy.c160022
  39. Rajesh Y, Sarkar D. 2021. Association of adipose tissue and adipokines with development of obesity-induced liver cancer. Int. J. Mol. Sci. 22: 2163.
  40. Deng Y, Scherer PE. 2010. Adipokines as novel biomarkers and regulators of the metabolic syndrome. Ann. N Y Acad. Sci. 1212: E1-E19. https://doi.org/10.1111/j.1749-6632.2010.05875.x
  41. An HM, Park SY, Lee DK, Kim JR, Cha MK, Lee SW, et al. 2011. Antiobesity and lipid-lowering effects of Bifidobacterium spp. in high fat diet-induced obese rats. Lipids Health Dis. 10: 116.
  42. Arias-Mutis OJ, Marrachelli VG, Ruiz-Sauri A, Alberola A, Morales JM, Such-Miquel L, et al. 2017. Development and characterization of an experimental model of diet-induced metabolic syndrome in rabbit. PLoS One 12: e0178315.
  43. Liu Y, Gao Y, Ma F, Sun M, Mu G, Tuo Y. 2020. The ameliorative effect of Lactobacillus plantarum Y44 oral administration on inflammation and lipid metabolism in obese mice fed with a high fat diet. Food Funct. 11: 5024-5039. https://doi.org/10.1039/D0FO00439A
  44. 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
  45. Stine RR, Shapira SN, Lim HW, Ishibashi J, Harms M, Won KJ, et al. 2016. EBF2 promotes the recruitment of beige adipocytes in white adipose tissue. Mol. Metab. 5: 57-65. https://doi.org/10.1016/j.molmet.2015.11.001
  46. Lee P, Werner CD, Kebebew E, Celi FS. 2014. Functional thermogenic beige adipogenesis is inducible in human neck fat. Int. J. Obes. 38: 170-176. https://doi.org/10.1038/ijo.2013.82
  47. Miyamoto J, Hasegawa S, Kasubuchi M, Ichimura A, Nakajima A, Kimura I. 2016. Nutritional signaling via free fatty acid receptors. Int. J. Mol. Sci. 17: 450-450. https://doi.org/10.3390/ijms17040450
  48. Ichimura A, Hasegawa S, Kasubuchi M, Kimura I. 2014. Free fatty acid receptors as therapeutic targets for the treatment of diabetes. Front. Pharmacol. 5: 236.
  49. Wang A, Si H, Liu D, Jiang H. 2011. Butyrate activates the cAMP-protein kinase A-cAMP response element-binding protein signaling pathway in Caco-2 cells. J. Nutr. 142: 1-6. https://doi.org/10.3945/jn.111.148155
  50. Wauson EM, Dbouk HA, Ghosh AB, Cobb MH. 2014. G protein-coupled receptors and the regulation of autophagy. Trends Endocrinol. Metab. 25: 274-282. https://doi.org/10.1016/j.tem.2014.03.006
  51. Barella LF, Jain S, Kimura T, Pydi SP. 2021. Metabolic roles of G protein-coupled receptor signaling in obesity and type 2 diabetes. FEBS J. 288: 2622-2644. https://doi.org/10.1111/febs.15800