Weissella cibaria MG5285 and Lactobacillus reuteri MG5149 attenuated fat accumulation in adipose and hepatic steatosis in high-fat diet-induced C57BL/6J obese mice
Background: Excessive consumption of dietary fat is closely related to obesity, diabetes, insulin resistance, cardiovascular disease, hypertension, and non-alcoholic fatty liver disease. Recently, probiotics have been highly proposed as biotherapeutic to treat and prevent diseases. Previously, there are studies that demonstrated the beneficial effects of probiotics against metabolic disorders, including obesity and diabetes.
Objective: We investigated the anti-obesity effect and mechanism of action of four human-derived lactic acid bacterial (LAB) strains (Lacticaseibacillus rhamnosus MG4502, Lactobacillus gasseri MG4524, Limosilactobacillus reuteri MG5149, and Weissella cibaria MG5285) in high-fat diet (HFD)-induced obese mice.
Design: Obesity was induced in mice over 8 weeks, with a 60% HFD. The four human-derived LAB strains (2 × 108 CFU/mouse) were orally administered to male C57BL/6J mice once daily for 8 weeks. Body weight, liver and adipose tissue (AT) weights, glucose tolerance, and serum biochemistry profiles were determined. After collecting the tissues, histopathological and Western blot analyses were conducted.
Results: Administration of these LAB strains resulted in decreased body weight, liver and AT weights, and glucose tolerance. Serum biochemistry profiles, including triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, and leptin, pro-inflammatory cytokines, improved. Hepatic steatosis and TG levels in liver tissue were significantly reduced. In addition, the size of adipocytes in epididymal tissue was significantly reduced. In epididymal tissues, Limosilactobacillus reuteri MG5149 and Weissella cibaria MG5285 groups showed a significantly reduced expression of lipogenic proteins, including peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, fatty acid synthase (FAS), and adipocyte-protein 2. In addition, sterol regulatory element-binding protein 1-c and its downstream protein FAS in the liver tissue were significantly decreased. These strains attenuated fat accumulation in the liver and AT by upregulating the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase in HFD-fed mice.
Conclusion: We suggest that L. reuteri MG5149 and W. cibaria MG5285 could be used as potential probiotic candidates to prevent obesity.
- Yan Y, Liu C, Zhao S, Wang X, Wang J, Zhang H, et al. Probiotic Bifidobacterium lactis V9 attenuates hepatic steatosis and inflammation in rats with non-alcoholic fatty liver disease. AMB Exp 2020; 10(1): 1–11. doi: 10.1186/s13568-020-01038-y
- Canfora EE, Meex RC, Venema K, Blaak EE. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol 2019; 15(5): 261–73. doi: 10.1038/s41574-019-0156-z
- de Almada CN, De Almada CN, Martinez RCR, de Souza Sant’Ana A. Characterization of the intestinal microbiota and its interaction with probiotics and health impacts. Appl Microbiol Biotechnol 2015; 99(10): 4175–99. doi: 10.1007/s00253-015-6582-5
- Zhao X, Zhang J, Yi S, Li X, Guo Z, Zhou X, et al. Lactobacillus plantarum CQPC02 prevents obesity in mice through the PPAR-α signaling pathway. Biomolecules 2019; 9(9): 407. doi: 10.3390/biom9090407
- Van Olden C, Groen AK, Nieuwdorp M. Role of intestinal microbiome in lipid and glucose metabolism in diabetes mellitus. Clinical Ther 2015; 37(6): 1172–7. doi: 10.1016/j.clinthera.2015.03.008
- Malard F, Dore J, Gaugler B, Mohty M. Introduction to host microbiome symbiosis in health and disease. Mucosal Immunol 2021; 14(3): 547–54. doi: 10.1038/s41385-020-00365-4
- Wilkins T, Sequoia J. Probiotics for gastrointestinal conditions: a summary of the evidence. Am Fam Physician 2017; 96(3): 170–8.
- Tojo R, Suárez A, Clemente MG, de los Reyes-Gavilán CG, Margolles A, Gueimonde M, et al. Intestinal microbiota in health and disease: role of bifidobacteria in gut homeostasis. World J Gastroenterol 2014; 20(41): 15163. doi: 10.3748/wjg.v20.i41.15163
- Reid G, Younes JA, Van der Mei HC, Gloor GB, Knight R, Busscher HJ. Microbiota restoration: natural and supplemented recovery of human microbial communities. Nat Rev Microbiol 2011; 9(1): 27–38. doi: 10.1038/nrmicro2473
- Kang JH, Yun SI, Park MH, Park JH, Jeong SY, Park H-O. Anti-obesity effect of Lactobacillus gasseri BNR17 in high-sucrose diet-induced obese mice. PLoS One 2013; 8(1): e54617. doi: 10.1371/journal.pone.0054617
- El Hage R, Hernandez-Sanabria E, Van de Wiele T. Emerging trends in ‘smart probiotics’: functional consideration for the development of novel health and industrial applications. Front Microbiol 2017; 8: 1889. doi: 10.3389/fmicb.2017.01889
- Nguyen TH, Kim Y, Kim JS, Jeong Y, Park HM, Kim JE, et al. Evaluating the cryoprotective encapsulation of the lactic acid bacteria in simulated gastrointestinal conditions. Biotechnol Bioprocess Eng 2020; 25: 287–92. doi: 10.1007/s12257-019-0406-x
- Li H, Liu F, Lu J, Shi J, Guan J, Yan F, et al. Probiotic mixture of Lactobacillus plantarum strains improves lipid metabolism and gut microbiota structure in high fat diet-fed mice. Front Microbiol 2020; 11: 512. doi: 10.3389/fmicb.2020.00512
- Andrikopoulos S, Blair AR, Deluca N, Fam BC, Proietto J. Evaluating the glucose tolerance test in mice. Am J Physiol Endocrinol Metab 2008; 295(6): E1323–32. doi: 10.1152/ajpendo.90617.2008
- Liang W, Menke AL, Driessen A, Koek GH, Lindeman JH, Stoop R, Havekes LM, Kleemann R, van den Hoek AM. Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology. PLoS One 2014; 9(12): e115922. doi: 10.1371/journal.pone.0115922
- Ding RX, Goh WR, Wu RN, Yue XQ, Luo X, Khine WWT, et al. Revisit gut microbiota and its impact on human health and disease. J Food Drug Anal 2019; 27(3): 623–31. doi: 10.1016/j.jfda.2018.12.012
- Elshaghabee FM, Ghadimi D, Habermann D, de Vrese M, Bockelmann W, Kaatsch HJ, et al. Effect of oral administration of Weissella confusa on fecal and plasma ethanol concentrations, lipids and glucose metabolism in wistar rats fed high fructose and fat diet. Hepat Med 2020; 12: 93–106. doi: 10.2147/HMER.S254195
- Conlon MA, Bird AR. The impact of diet and lifestyle on gut microbiota and human health. Nutrients 2015; 7(1): 17–44. doi: 10.3390/nu7010017
- Karimi G, Sabran MR, Jamaluddin R, Parvaneh K, Mohtarrudin N, Ahmad Z, et al. The anti-obesity effects of Lactobacillus casei strain Shirota versus Orlistat on high fat diet-induced obese rats. Food Nutr Res 2015; 59(1): 29273. doi: 10.3402/fnr.v59.29273
- Moon YJ, Baik SH, Cha YS. Lipid-lowering effects of Pediococcus acidilactici M76 isolated from Korean traditional makgeolli in high fat diet-induced obese mice. Nutrients 2014; 6(3): 1016–28. doi: 10.3390/nu6031016
- Dahiya DK, Puniya M, Shandilya UK, Dhewa T, Kumar N, Kumar S, et al. Gut microbiota modulation and its relationship with obesity using prebiotic fibers and probiotics: a review. Front Microbiol 2017; 8: 563. doi: 10.3389/fmicb.2017.00563
- Wang J, Tang H, Zhang C, Zhao Y, Derrien M, Rocher E, et al. Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice. ISME J 2015; 9(1): 1–15. doi: 10.1038/ismej.2014.99
- Winzell MS, Ahrén B. The high-fat diet–fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes 2004; 53(Suppl 3): S215–S9. doi: 10.2337/diabetes.53.suppl_3.S215
- Borel A, Nazare J, Smith J, Aschner P, Barter P, Van Gaal L, et al. Visceral, subcutaneous abdominal adiposity and liver fat content distribution in normal glucose tolerance, impaired fasting glucose and/or impaired glucose tolerance. Int J Obes 2015; 39(3): 495–501. doi: 10.1038/ijo.2014.163
- Foley KP, Zlitni S, Denou E, Duggan BM, Chan RW, Stearns JC, et al. Long term but not short term exposure to obesity related microbiota promotes host insulin resistance. Nat Commun 2018; 9(1): 1–15. doi: 10.1038/s41467-018-07146-5
- Lim SM, Jeong JJ, Woo KH, Han MJ, Kim DH. Lactobacillus sakei OK67 ameliorates high-fat diet–induced blood glucose intolerance and obesity in mice by inhibiting gut microbiota lipopolysaccharide production and inducing colon tight junction protein expression. Nutr Res 2016; 36(4): 337–48. doi: 10.1016/j.nutres.2015.12.001
- Eslamparast T, Eghtesad S, Hekmatdoost A, Poustchi H. Probiotics and nonalcoholic fatty liver disease. Middle East J Dig Dis 2013; 5(3): 129.
- Caesar R, Manieri M, Kelder T, Boekschoten M, Evelo C, Müller M, et al. A combined transcriptomics and lipidomics analysis of subcutaneous, epididymal and mesenteric adipose tissue reveals marked functional differences. PLoS One 2010; 5(7): e11525. doi: 10.1371/journal.pone.0011525
- Nido SA, Shituleni SA, Mengistu BM, Liu Y, Khan AZ, Gan F, et al. Effects of selenium-enriched probiotics on lipid metabolism, antioxidative status, histopathological lesions, and related gene expression in mice fed a high-fat diet. Biol Trace Elem Res 2016; 171(2): 399–409. doi: 10.1007/s12011-015-0552-8
- Ok E, Do GM, Lim Y, Park JE, Park YJ, Kwon O. Pomegranate vinegar attenuates adiposity in obese rats through coordinated control of AMPK signaling in the liver and adipose tissue. Lipids Health Dis 2013; 12(1): 163. doi: 10.1186/1476-511X-12-163
- Xie N, Cui Y, Yin YN, Zhao X, Yang JW, Wang ZG, et al. Effects of two Lactobacillus strains on lipid metabolism and intestinal microflora in rats fed a high-cholesterol diet. BMC Complement Altern Med 2011; 11(1): 53. doi: 10.1186/1472-6882-11-53
- Ríos-Lugo MJ, Cano P, Jiménez-Ortega V, Fernández-Mateos MP, Scacchi PA, Cardinali DP, et al. Melatonin effect on plasma adiponectin, leptin, insulin, glucose, triglycerides and cholesterol in normal and high fat–fed rats. J Pineal Res 2010; 49(4): 342–8. doi: 10.1111/j.1600-079X.2010.00798.x
- Ahren B, Mansson S, Gingerich RL, Havel PJ. Regulation of plasma leptin in mice: influence of age, high-fat diet, and fasting. Am J Physiol Regul Integr Comp Physiol 1997; 273(1): R113–20. doi: 10.1152/ajpregu.1997.273.1.R113
- Kim SW, Park KY, Kim B, Kim E, Hyun CK. Lactobacillus rhamnosus GG improves insulin sensitivity and reduces adiposity in high-fat diet-fed mice through enhancement of adiponectin production. Biochem Biophys Res Commun 2013; 431(2): 258–63. doi: 10.1016/j.bbrc.2012.12.121
- Pilling D, Karhadkar TR, Gomer RH. High-fat diet–induced adipose tissue and liver inflammation and steatosis in mice are reduced by inhibiting sialidases. Am J Pathol 2020; 191(1): 131–43. doi: 10.1016/j.ajpath.2020.09.011
- Alves-Bezerra M, Cohen DE. Triglyceride metabolism in the liver. Compr Physiol 2011; 8(1): 1–22. doi: 10.1002/cphy.c170012
- Esposito E, Iacono A, Bianco G, Autore G, Cuzzocrea S, Vajro P, et al. Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats. J Nutr 2009; 139(5): 905–11. doi: 10.3945/jn.108.101808
- Kim KY, Lee HN, Kim YJ, Park T. Garcinia cambogia extract ameliorates visceral adiposity in C57BL/6J mice fed on a high-fat diet. Biosci Biotechnol Biochem 2008; 72: 80072-1-9. doi: 10.1271/bbb.80072
- Saponaro C, Gaggini M, Carli F, Gastaldelli A. The subtle balance between lipolysis and lipogenesis: a critical point in metabolic homeostasis. Nutrients 2015; 7(11): 9453–74. doi: 10.3390/nu7115475
- Choi BH, Ahn IS, Kim Y, Park JW, Lee SY, Hyun CK, et al. Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte. Exp Mol Med 2006; 38(6): 599–605. doi: 10.1038/emm.2006.71
- Mottillo EP, Desjardins EM, Crane JD, Smith BK, Green AE, Ducommun S, et al. Lack of adipocyte AMPK exacerbates insulin resistance and hepatic steatosis through brown and beige adipose tissue function. Cell Metab 2016; 24(1): 118–29. doi: 10.1016/j.cmet.2016.06.006
- Hossain M, Park DS, Rahman M, Ki SJ, Lee YR, Imran K, et al. Bifidobacterium longum DS0956 and Lactobacillus rhamnosus DS0508 culture-supernatant ameliorate obesity by inducing thermogenesis in obese-mice. Benef Microbes 2020; 11(4): 361–73. doi: 10.3920/BM2019.0179
- Kadooka Y, Sato M, Imaizumi K, Ogawa A, Ikuyama K, Akai Y, et al. Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. Eur J Clin Nutr 2010; 64(6): 636–43. doi: 10.1038/ejcn.2010.19
- Qiao Y, Sun J, Xia S, Li L, Li Y, Wang P, et al. Effects of different Lactobacillus reuteri on inflammatory and fat storage in high-fat diet-induced obesity mice model. J Funct Foods 2015; 14: 424–34. doi: 10.1016/j.jff.2015.02.013
- Ahn SB, Park HE, Lee SM, Kim SY, Shon MY, Lee WK. Characteristics and immuno-modulatory effects of Weissella cibaria JW15 isolated from Kimchi, Korea traditional fermented food, for probiotic use. J Biomed Res 2013; 14(4): 206–11. doi: 10.12729/jbr.2013.14.4.206
- Yu HS, Lee NK, Choi AJ, Choe JS, Bae CH, Paik HD. Antagonistic and antioxidant effect of probiotic Weissella cibaria JW15. Food Sci Biotechnol 2019; 28(3): 851–5. doi: 10.1007/s10068-018-0519-6
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors retain copyright of their work, with first publication rights granted to SNF Swedish Nutrition Foundation. Read the full Copyright- and Licensing Statement.