Effects of heat-inactivated <i>Lactobacillus gasseri</i> TMC0356 on liver lipid metabolism in rats with metabolic syndrome and its possible mechanism_West China Medical Journal

Authors：

SHUI Qihang ¹ , SHI Lei ² , HE Fang ³ , LI Ming ³ , HUANG Chengyu ³ , JING Xiaofan ² ,  HU Wen ¹

1. West China School of Medicine, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
3. West China School of Public Health, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

HU Wen, Email: wendy_nutrition@163.com

Keywords：

Metabolic syndrome; heat-inactivated Lactobacillus gasseri TMC0356; fatty acid synthase; sterol regulatory element binding protein -1c; carnitine palmitoyltransferase -1; peroxisome proliferator activated receptor-α

DOI：

10.7507/1002-0179.202108281

Video：

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Objective To explore the effects of heat-inactivated Lactobacillus gasseri TMC0356 on liver lipid metabolism in rats with metabolic syndrome (MS) and its possible mechanism. Methods Sixty male Sprague-Dawley rats were selected. Rats were randomly divided into 5 groups, including control group, MS model group and three TMC0356 test groups (low-, medium- and high-dose groups). The rats in each group were fed with different diets for 7 days, and the liver was dissected and removed after 15 weeks. The mRNA and protein expression levels of peroxisome hyperbioactive receptor-α (PPAR-α), sterol regulatory element binding protein-1c (REBP-1c), fatty acid synthase (FAS) and carnitine lipoacyltransferase-1 (CPT-1) genes in liver were detected. Results There was no significant difference in the mRNA expression of PPAR-α, SREBP-1c or CPT-1 among the five groups (P>0.05). The mRNA expression of FAS in low-dose TMC0356 test group was lower than that in MS model group (P=0.011), medium-dose TMC0356 test group (P=0.042) and high-dose TMC0356 test group (P=0.009). There was no significant difference in the expression of FAS mRNA between other groups (P>0.05). There was no significant difference in the protein expression of PPAR-α, SREBP-1c or FAS among the five groups (P>0.05). The protein expression of CPT-1 in low-dose TMC0356 test group was higher than that in control group (P=0.033) and high-dose TMC0356 test group (P=0.043). There was no significant difference in the protein expression of CPT-1 between the other groups (P>0.05). Conclusion Heat-inactivated Lactobacillus gasseri TMC0356 may improve the symptoms of metabolic disorder in rats by suppressing appetite, improving insulin resistance, and downregulating the expression of key fat metabolism genes such as FAS and SREBP-1c.

Citation： SHUI Qihang, SHI Lei, HE Fang, LI Ming, HUANG Chengyu, JING Xiaofan, HU Wen. Effects of heat-inactivated Lactobacillus gasseri TMC0356 on liver lipid metabolism in rats with metabolic syndrome and its possible mechanism. West China Medical Journal, 2022, 37(3): 437-442. doi: 10.7507/1002-0179.202108281 Copy

1.	Zhang J, Wu H, Wang R. Metabolic syndrome and esophageal cancer risk: a systematic review and meta-analysis. Diabetol Metab Syndr, 2021, 13(1): 8.
2.	Khorraminezhad L, Rudkowska I. Effect of yogurt consumption on metabolic syndrome risk factors: a narrative review. Curr Nutr Rep, 2021, 10(1): 83-92.
3.	Huang WC, Lin CL, Hsu YJ, et al. Inulin and fibersol-2 combined have hypolipidemic effects on high cholesterol diet-induced hyperlipidemia in hamsters. Molecules, 2016, 21(3): 313.
4.	Ferrario C, Statello R, Carnevali L, et al. How to feed the mammalian gut microbiota: bacterial and metabolic modulation by dietary fibers. Front Microbiol, 2017, 8: 1749.
5.	Castleberry T, Irvine C, Gordon R, et al. The dose effect of whey protein on glycemic control in adults with insulin resistance. Int J Food Sci Biotechnol, 2020, 5(4): 62-67.
6.	Kawase M, He F, Kubota A, et al. Inhibitory effect of Lactobacillus gasseri TMC0356 and Lactobacillus GG on enhanced vascular permeability of nasal mucosa in experimental allergic rhinitis of rats. Biosci Biotechnol Biochem, 2006, 70(12): 3025-3030.
7.	Kawase M, He F, Kubota A, et al. Effect of fermented milk prepared with two probiotic strains on Japanese cedar pollinosis in a double-blind placebo-controlled clinical study. Int J Food Microbiol, 2009, 128(3): 429-434.
8.	Kubota A, He F, Kawase M, et al. Lactobacillus strains stabilize intestinal microbiota in Japanese cedar pollinosis patients. Microbiol Immunol, 2009, 53(4): 198-205.
9.	Kawase M, He F, Kubota A, et al. Heat-killed Lactobacillus gasseri TMC0356 protects mice against influenza virus infection by stimulating gut and respiratory immune responses. FEMS Immunol Med Microbiol, 2012, 64(2): 280-288.
10.	Kawase M, He F, Miyazawa K, et al. Orally administered heat-killed Lactobacillus gasseri TMC0356 can upregulate cell-mediated immunity in senescence-accelerated mice. FEMS Microbiol Lett, 2012, 326(2): 125-130.
11.	Shi L, Li M, Miyazawa K, et al. Effects of heat-inactivated Lactobacillus gasseri TMC0356 on metabolic characteristics and immunity of rats with the metabolic syndrome. Br J Nutr, 2013, 109(2): 263-272.
12.	Canfora EE, Meex RCR, Venema K, et al. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol, 2019, 15(5): 261-273.
13.	Pozzi S, Boergesen M, Sinha S, et al. Peroxisome proliferator-activated receptor-alpha is a functional target of p63 in adult human keratinocytes. J Invest Dermatol, 2009, 129(10): 2376-2385.
14.	Wang Y, Viscarra J, Kim SJ, et al. Transcriptional regulation of hepatic lipogenesis. Nat Rev Mol Cell Biol, 2015, 16(11): 678-689.
15.	Schweizer E, Hofmann J. Microbial typeⅠfatty acid synthases (fas): major players in a network of cellular fas systems. Microbiol Mol Biol Rev, 2004, 68(3): 501-517.
16.	Jin YJ, Li SZ, Zhao ZS, et al. Carnitine palmitoyltransferase-1 (CPT-1) activity stimulation by cerulenin via sympathetic nervous system activation overrides cerulenin’s peripheral effect. Endocrinology, 2004, 145(7): 3197-3204.
17.	Kwon H, Kim D, Kim JS. Body fat distribution and the risk of incident metabolic syndrome: a longitudinal cohort study. Sci Rep, 2017, 7(1): 10955.
18.	Bernini LJ, Simão AN, Alfieri DF, et al. Beneficial effects of Bifidobacterium lactis on lipid profile and cytokines in patients with metabolic syndrome: a randomized trial. Effects of probiotics on metabolic syndrome. Nutrition, 2016, 32(6): 716-719.
19.	Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications-a review. Nutr J, 2014, 13: 17.
20.	Bougarne N, Weyers B, Desmet SJ, et al. Molecular actions of PPAR-α in lipid metabolism and inflammation. Endocr Rev, 2018, 39(5): 760-802.
21.	Mohd MA, Ahmad Norudin NA, Muhammad TST. Transcriptional regulation of retinol binding protein 4 by Interleukin-6 via peroxisome proliferator-activated receptor α and CCAAT/Enhancer binding proteins. Mol Cell Endocrinol, 2020, 505: 110702.
22.	Cheng C, Geng F, Cheng X, et al. Lipid metabolism reprogramming and its potential targets in cancer. Cancer Commun (Lond), 2018, 38(1): 27.
23.	Shimomura I, Bashmakov Y, Ikemoto S, et al. Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes. Proc Natl Acad Sci USA, 1999, 96(24): 13656-13661.
24.	Cagen LM, Deng X, Wilcox HG, et al. Insulin activates the rat sterol-regulatory-element-binding protein 1c (SREBP-1c) promoter through the combinatorial actions of SREBP-, LXR, Sp-1 and NF-Y cis-acting elements. Biochem J, 2005, 385(Pt 1): 207-216.
25.	Ruiz R, Jideonwo V, Ahn M, et al. Sterol regulatory element-binding protein-1 (SREBP-1) is required to regulate glycogen synthesis and gluconeogenic gene expression in mouse liver. J Biol Chem, 2014, 289(9): 5510-5517.
26.	Loftus TM, Jaworsky DE, Frehywot GL, et al. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science, 2000, 288(5475): 2379-2381.
27.	Park DY, Ahn YT, Huh CS, et al. Dual probiotic strains suppress high fructose-induced metabolic syndrome. World J Gastroenterol, 2013, 19(2): 274-283.
28.	Oh YJ, Kim HJ, Kim TS, et al. Effects of Lactobacillus plantarum PMO 08 alone and combined with chia seeds on metabolic syndrome and parameters related to gut health in high-fat diet-induced obese mice. J Med Food, 2019, 22(12): 1199-1207.

1. Zhang J, Wu H, Wang R. Metabolic syndrome and esophageal cancer risk: a systematic review and meta-analysis. Diabetol Metab Syndr, 2021, 13(1): 8.
2. Khorraminezhad L, Rudkowska I. Effect of yogurt consumption on metabolic syndrome risk factors: a narrative review. Curr Nutr Rep, 2021, 10(1): 83-92.
3. Huang WC, Lin CL, Hsu YJ, et al. Inulin and fibersol-2 combined have hypolipidemic effects on high cholesterol diet-induced hyperlipidemia in hamsters. Molecules, 2016, 21(3): 313.
4. Ferrario C, Statello R, Carnevali L, et al. How to feed the mammalian gut microbiota: bacterial and metabolic modulation by dietary fibers. Front Microbiol, 2017, 8: 1749.
5. Castleberry T, Irvine C, Gordon R, et al. The dose effect of whey protein on glycemic control in adults with insulin resistance. Int J Food Sci Biotechnol, 2020, 5(4): 62-67.
6. Kawase M, He F, Kubota A, et al. Inhibitory effect of Lactobacillus gasseri TMC0356 and Lactobacillus GG on enhanced vascular permeability of nasal mucosa in experimental allergic rhinitis of rats. Biosci Biotechnol Biochem, 2006, 70(12): 3025-3030.
7. Kawase M, He F, Kubota A, et al. Effect of fermented milk prepared with two probiotic strains on Japanese cedar pollinosis in a double-blind placebo-controlled clinical study. Int J Food Microbiol, 2009, 128(3): 429-434.
8. Kubota A, He F, Kawase M, et al. Lactobacillus strains stabilize intestinal microbiota in Japanese cedar pollinosis patients. Microbiol Immunol, 2009, 53(4): 198-205.
9. Kawase M, He F, Kubota A, et al. Heat-killed Lactobacillus gasseri TMC0356 protects mice against influenza virus infection by stimulating gut and respiratory immune responses. FEMS Immunol Med Microbiol, 2012, 64(2): 280-288.
10. Kawase M, He F, Miyazawa K, et al. Orally administered heat-killed Lactobacillus gasseri TMC0356 can upregulate cell-mediated immunity in senescence-accelerated mice. FEMS Microbiol Lett, 2012, 326(2): 125-130.
11. Shi L, Li M, Miyazawa K, et al. Effects of heat-inactivated Lactobacillus gasseri TMC0356 on metabolic characteristics and immunity of rats with the metabolic syndrome. Br J Nutr, 2013, 109(2): 263-272.
12. Canfora EE, Meex RCR, Venema K, et al. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol, 2019, 15(5): 261-273.
13. Pozzi S, Boergesen M, Sinha S, et al. Peroxisome proliferator-activated receptor-alpha is a functional target of p63 in adult human keratinocytes. J Invest Dermatol, 2009, 129(10): 2376-2385.
14. Wang Y, Viscarra J, Kim SJ, et al. Transcriptional regulation of hepatic lipogenesis. Nat Rev Mol Cell Biol, 2015, 16(11): 678-689.
15. Schweizer E, Hofmann J. Microbial typeⅠfatty acid synthases (fas): major players in a network of cellular fas systems. Microbiol Mol Biol Rev, 2004, 68(3): 501-517.
16. Jin YJ, Li SZ, Zhao ZS, et al. Carnitine palmitoyltransferase-1 (CPT-1) activity stimulation by cerulenin via sympathetic nervous system activation overrides cerulenin’s peripheral effect. Endocrinology, 2004, 145(7): 3197-3204.
17. Kwon H, Kim D, Kim JS. Body fat distribution and the risk of incident metabolic syndrome: a longitudinal cohort study. Sci Rep, 2017, 7(1): 10955.
18. Bernini LJ, Simão AN, Alfieri DF, et al. Beneficial effects of Bifidobacterium lactis on lipid profile and cytokines in patients with metabolic syndrome: a randomized trial. Effects of probiotics on metabolic syndrome. Nutrition, 2016, 32(6): 716-719.
19. Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications-a review. Nutr J, 2014, 13: 17.
20. Bougarne N, Weyers B, Desmet SJ, et al. Molecular actions of PPAR-α in lipid metabolism and inflammation. Endocr Rev, 2018, 39(5): 760-802.
21. Mohd MA, Ahmad Norudin NA, Muhammad TST. Transcriptional regulation of retinol binding protein 4 by Interleukin-6 via peroxisome proliferator-activated receptor α and CCAAT/Enhancer binding proteins. Mol Cell Endocrinol, 2020, 505: 110702.
22. Cheng C, Geng F, Cheng X, et al. Lipid metabolism reprogramming and its potential targets in cancer. Cancer Commun (Lond), 2018, 38(1): 27.
23. Shimomura I, Bashmakov Y, Ikemoto S, et al. Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes. Proc Natl Acad Sci USA, 1999, 96(24): 13656-13661.
24. Cagen LM, Deng X, Wilcox HG, et al. Insulin activates the rat sterol-regulatory-element-binding protein 1c (SREBP-1c) promoter through the combinatorial actions of SREBP-, LXR, Sp-1 and NF-Y cis-acting elements. Biochem J, 2005, 385(Pt 1): 207-216.
25. Ruiz R, Jideonwo V, Ahn M, et al. Sterol regulatory element-binding protein-1 (SREBP-1) is required to regulate glycogen synthesis and gluconeogenic gene expression in mouse liver. J Biol Chem, 2014, 289(9): 5510-5517.
26. Loftus TM, Jaworsky DE, Frehywot GL, et al. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science, 2000, 288(5475): 2379-2381.
27. Park DY, Ahn YT, Huh CS, et al. Dual probiotic strains suppress high fructose-induced metabolic syndrome. World J Gastroenterol, 2013, 19(2): 274-283.
28. Oh YJ, Kim HJ, Kim TS, et al. Effects of Lactobacillus plantarum PMO 08 alone and combined with chia seeds on metabolic syndrome and parameters related to gut health in high-fat diet-induced obese mice. J Med Food, 2019, 22(12): 1199-1207.

West China Medical Journal

Effects of heat-inactivated Lactobacillus gasseri TMC0356 on liver lipid metabolism in rats with metabolic syndrome and its possible mechanism

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