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Anti-obesity effect of Lactobacillus gasseri SBT2055 accompanied by inhibition of pro-inflammatory gene expression in the visceral adipose tissue in diet-induced obese mice

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Abstract

Purpose

Probiotic Lactobacillus gasseri SBT2055 (LG2055) has an anti-obesity effect although it is unknown whether the effect influences inflammatory responses in adipose tissue and lipid metabolism in the liver, which are considered substantially relevant to adiposity.

Methods

C57BL/6 mice were fed a 10 %-fat diet containing LG2055 cells for 24 weeks. We then studied body weight, fat tissue mass, liver fat content and inflammatory genes in the adipose tissue, and lipogenic and lipolytic genes in the liver.

Results

Consumption of LG2055 resulted in a significant reduction in body weight and fat tissue mass (epididymal and perirenal/retroperitoneal), with a lowered level of triglyceride content in the liver. DNA microarray analysis showed that LG2055 generally inhibited the up-regulation of pro-inflammatory genes, including CCL2 and CCR2, in the epididymal adipose tissue. In the liver, LG2055 tended to inhibit lipogenic gene up-regulation, including ACC1, FAS and SREBP1, but LG2055 did not markedly alter lipolytic genes. Real-time PCR analysis confirmed the DNA microarray results in part, showing a significant reduction in the mRNA expression of CCL2 in the epididymal adipose tissue, and a downward tendency in FAS mRNA expression in the liver, in the LG2055-fed group.

Conclusions

LG2055 significantly prevented body weight gain, fat accumulation and pro-inflammatory gene expression in the adipose tissue. Relatively lower triglyceride levels and reduced expression of lipogenic genes were also observed in the liver. It is suggested that improvement in the inflammatory state of the adipose tissue might be a possible mechanism underlying the anti-obesity effect of LG2055.

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References

  1. WHO (2012) WHO | obesity and overweight. http://www.who.int/mediacentre/factsheets/fs311/en/index.html. Accessed 21 Feb 2013

  2. Fox CS, Massaro JM, Hoffmann U et al (2007) Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham heart study. Circulation 116:39–48

    Article  Google Scholar 

  3. Ford ES, Williamson DF, Liu S (1997) Weight change and diabetes incidence: findings from a national cohort of US adults. Am J Epidemiol 146:214–222

    Article  CAS  Google Scholar 

  4. Liu B, Balkwill A, Reeves G, Beral V (2010) Body mass index and risk of liver cirrhosis in middle aged UK women: prospective study. BMJ 340:c912

    Article  Google Scholar 

  5. Hubert HB, Feinleib M, McNamara PM, Castelli WP (1983) Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham heart study. Circulation 67:968–977

    Article  CAS  Google Scholar 

  6. Huffman D, Barzilai N (2009) Role of visceral adipose tissue in aging. Biochim Biophys Acta 1790:1117–1123

    Article  CAS  Google Scholar 

  7. Gupta A, Gupta V (2010) Metabolic syndrome: what are the risks for humans? Biosci Trends 4:204–212

    Google Scholar 

  8. Horton ES (2009) Effects of lifestyle changes to reduce risks of diabetes and associated cardiovascular risks: results from large scale efficacy trials. Obesity (Silver Spring) 17(Suppl 3):S43–S48

    Article  Google Scholar 

  9. Thomas CM, Versalovic J (2010) Probiotics-host communication: modulation of signaling pathways in the intestine. Gut microbes 1:148–163

    Article  Google Scholar 

  10. Lye HS, Kuan CY, Ewe JA, Fung WY, Liong MT (2009) The improvement of hypertension by probiotics: effects on cholesterol, diabetes, renin, and phytoestrogens. Int J Mol Sci 10:3755–3775

    Article  CAS  Google Scholar 

  11. Mallappa RH, Rokana N, Duary RK, Panwar H, Batish VK, Grover S (2012) Management of metabolic syndrome through probiotic and prebiotic interventions. Indian J Endocrinol Metab 16:20–27

    CAS  Google Scholar 

  12. Lee HY, Park JH, Seok SH, Baek MW, Kim DJ, Lee KE, Paek KS, Lee Y, Park JH (2006) Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. Biochim Biophys Acta 1761:736–744

    Article  CAS  Google Scholar 

  13. Lee K, Paek K, Lee HY, Park JH, Lee Y (2007) Antiobesity effect of trans-10, cis-12-conjugated linoleic acid-producing Lactobacillus plantarum PL62 on diet-induced obese mice. J Appl Microbiol 103:1140–1146

    Article  CAS  Google Scholar 

  14. Kondo S, Xiao J, Satoh T, Odamaki T, Takahashi S, Sugahara H, Yaeshima T, Iwatsuki K, Kamei A, Abe K (2010) Antiobesity effects of Bifidobacterium breve strain b-3 supplementation in a mouse model with high-fat diet-induced obesity. Biosci Biotechnol Biochem 74:1656–1661

    Article  CAS  Google Scholar 

  15. Aronsson L, Huang Y, Parini P, Korach-André M, Håkansson J, Gustafsson J-Å, Pettersson S, Arulampalam V, Rafter J (2010) Decreased fat storage by Lactobacillus paracasei is associated with increased levels of angiopoietin-like 4 protein (ANGPTL4). PLoS One 5:e13087

    Article  Google Scholar 

  16. Sato M, Uzu K, Yoshida T, Hamad EM, Kawakami H, Matsuyama H, Abd El-Gawad IA, Imaizumi K (2008) Effects of milk fermented by Lactobacillus gasseri SBT2055 on adipocyte size in rats. Br J Nutr 99:1013–1017

    Article  CAS  Google Scholar 

  17. Hamad EM, Sato M, Uzu K, Yoshida T, Higashi S, Kawakami H, Kadooka Y, Matsuyama H, Abd El-Gawad IA, Imaizumi K (2009) Milk fermented by Lactobacillus gasseri SBT2055 influences adipocyte size via inhibition of dietary fat absorption in Zucker rats. Br J Nutr 101:716–724

    Article  CAS  Google Scholar 

  18. Kadooka Y, Ogawa A, Ikuyama K, Sato M (2011) The probiotic Lactobacillus gasseri SBT2055 inhibits enlargement of visceral adipocytes and upregulation of serum soluble adhesion molecule (sICAM-1) in rats. Int Dairy J 21:623–627

    Article  CAS  Google Scholar 

  19. Kadooka Y, Sato M, Imaizumi K, Ogawa A, Ikuyama K, Akai Y, Okano M, Kagoshima M, Tsuchida T (2010) Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. Eur J Clin Nutr 64:636–643

    Article  CAS  Google Scholar 

  20. Fujiwara S, Seto Y, Kimura A, Hashiba H (2001) Establishment of orally-administered Lactobacillus gasseri SBT2055SR in the gastrointestinal tract of humans and its influence on intestinal microflora and. J Appl Microbiol 90:343–352

    Article  CAS  Google Scholar 

  21. Imai E, Fukui K, Ohta N, Tomitsuka T (2002) Effects of Lactobacillus gasseri SBT2055 on dextran sulfate sodium-induced ulcerative colitis model in rats. Biosci Microflora 21:179–183

    Google Scholar 

  22. Bastard J, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17:4–12

    CAS  Google Scholar 

  23. Hotamisligil GS (2006) Inflammation and metabolic disorders. Nature 444:860–867

    Article  CAS  Google Scholar 

  24. Ding S, Chi MM, Scull BP, Rigby R, Schwerbrock NMJ, Magness S, Jobin C, Lund PK (2010) High-fat diet: bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PLoS One 5:e12191

    Article  Google Scholar 

  25. Cani PD, Amar J, Iglesias MA et al (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56:1761–1772

    Article  CAS  Google Scholar 

  26. Yang ZH, Miyahara H, Takeo J, Katayama M (2012) Diet high in fat and sucrose induces rapid onset of obesity-related metabolic syndrome partly through rapid response of genes involved in lipogenesis, insulin signalling and inflammation in mice. Diabetol Metab Syndr 4:32

    Article  CAS  Google Scholar 

  27. American Institute of Nutrition (1977) Report of the American Institute of Nutrition ad hoc committee on standards for nutritional studies. J Nutr 107:1340–1348

    Google Scholar 

  28. Folch J, Lees M, Sloane-Stanley G (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509

    CAS  Google Scholar 

  29. Lumeng CN, Bodzin JL, Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117:175–184

    Article  CAS  Google Scholar 

  30. Kanda H, Tateya S, Tamori Y et al (2006) MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 116:1494–1505

    Article  CAS  Google Scholar 

  31. Weisberg S, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K, Charo I, Leibel RL, Ferrante AWJ (2006) CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 116:115–124

    Article  CAS  Google Scholar 

  32. Wellen K, Hotamisligil G (2003) Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 112:1785–1788

    Article  CAS  Google Scholar 

  33. Suganami T, Nishida J, Ogawa Y (2005) A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol 25:2062–2068

    Article  CAS  Google Scholar 

  34. Shoelson SSE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. J Clin Invest 116:1793–1801

    Article  CAS  Google Scholar 

  35. Tamura Y, Sugimoto M, Murayama T, Minami M, Nishikaze Y, Ariyasu H, Akamizu T, Kita T, Yokode M, Arai H (2010) C–C chemokine receptor 2 inhibitor improves diet-induced development of insulin resistance and hepatic steatosis in mice. J Atheroscler Thromb 17:219–228

    Article  CAS  Google Scholar 

  36. Li H, Lelliott C, Håkansson P, Ploj K, Tuneld A, Verolin-Johansson M, Benthem L, Carlsson B, Storlien L, Michaëlsson E (2008) Intestinal, adipose, and liver inflammation in diet-induced obese mice. Metabolism 57:1704–1710

    Article  CAS  Google Scholar 

  37. DeLany JP, Windhauser MM, Champagne CM, Bray GA (2000) Differential oxidation of individual dietary fatty acids in humans. Am J Clin Nutr 72:905–911

    CAS  Google Scholar 

  38. Tjonneland A, Overvad K, Bergmann MM et al (2009) Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case-control study within a European prospective cohort study. Gut 58:1606–1611

    Article  Google Scholar 

  39. Postic C, Girard J (2008) Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest 118:829–838

    Article  CAS  Google Scholar 

  40. Mao J, DeMayo FJ, Li H, Abu-Elheiga L, Gu Z, Shaikenov TE, Kordari P, Chirala SS, Heird WC, Wakil SJ (2006) Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis. Proc Natl Acad Sci USA 103:8552–8557

    Article  CAS  Google Scholar 

  41. Ntambi JM, Miyazaki M, Stoehr JP, Lan H, Kendziorski CM, Yandell BS, Song Y, Cohen P, Friedman JM, Attie AD (2002) Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc Natl Acad Sci USA 99:11482–11486

    Article  CAS  Google Scholar 

  42. Jiang G, Li Z, Liu F et al (2005) Prevention of obesity in mice by antisense oligonucleotide inhibitors of stearoyl-CoA desaturase-1. J Clin Invest 115:1030–1038

    Article  CAS  Google Scholar 

  43. Guerre-Millo M, Gervois P (2000) Peroxisome proliferator-activated receptor α activators improve insulin sensitivity and reduce adiposity. J Biol Chem 275:16638–16642

    Article  CAS  Google Scholar 

  44. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ (2005) Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 115:1343–1351

    Article  CAS  Google Scholar 

  45. Sanal MG (2008) The blind men “see” the elephant-the many faces of fatty liver disease. World J Gastroenterol 14:831–844

    Article  CAS  Google Scholar 

  46. Gibbons GF (1990) Assembly and secretion of hepatic very-low-density lipoprotein. Biochem J 268:1–13

    CAS  Google Scholar 

  47. Wolfe RR, Durkot MJ (1985) Role of very low density lipoproteins in the energy metabolism of the rat. J Lipid Res 26:210–217

    CAS  Google Scholar 

  48. Raabe M, Véniant MM, Sullivan MA, Zlot CH, Björkegren J, Nielsen LB, Wong JS, Hamilton RL, Young SG (1999) Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice. J Clin Invest 103:1287–1298

    Article  CAS  Google Scholar 

  49. Hoffmann M, Rath E, Hölzlwimmer G, Quintanilla-Martinez L, Loach D, Tannock G, Haller D (2008) Lactobacillus reuteri 100–23 transiently activates intestinal epithelial cells of mice that have a complex microbiota during early stages of colonization. J Nutr 138:1684–1691

    CAS  Google Scholar 

  50. Li N, Russell WM, Douglas-escobar M, Hauser N, Lopez M, Neu J (2009) Live and heat-killed Lactobacillus rhamnosus GG: effects on proinflammatory and anti-inflammatory cytokines/chemokines in gastrostomy-fed infant rats. Pediatr Res 66:203–207

    Article  CAS  Google Scholar 

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Acknowledgments

We are grateful to Ken Ukibe, Maya Yamashita, Michio Kawano, Tomohiro Hosoya, Hiroshi Uenishi and Fumihiko Sakai for their skillful collaboration and useful suggestions. We also thank Emiko Yamaguchi for preparing the experimental diets and technical assistance, and YBS Co. Ltd. for animal care. Contribution: all authors contributed to the experimental design. MM and AO mainly performed the experiments. YK supervized the study design. SH assisted with the animal experiment. MM and YK wrote the manuscript.

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Authors and Affiliations

  1. Milk Science Research Institute, Megmilk Snow Brand Co. Ltd., 1-1-2 Minamidai, Kawagoe, Saitama, Japan

    Masaya Miyoshi, Akihiro Ogawa, Satoshi Higurashi & Yukio Kadooka

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  1. Masaya Miyoshi
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  2. Akihiro Ogawa
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  3. Satoshi Higurashi
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  4. Yukio Kadooka
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Correspondence to Masaya Miyoshi.

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Miyoshi, M., Ogawa, A., Higurashi, S. et al. Anti-obesity effect of Lactobacillus gasseri SBT2055 accompanied by inhibition of pro-inflammatory gene expression in the visceral adipose tissue in diet-induced obese mice. Eur J Nutr 53, 599–606 (2014). https://doi.org/10.1007/s00394-013-0568-9

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  • DOI: https://doi.org/10.1007/s00394-013-0568-9

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