Background/Aims
Dietary factors and intestinal bacteria play an important role in the rapidly increasing
incidence of obesity and its associated conditions, such as steatosis and insulin
resistance. In the current study, we evaluated the effect of probiotics, and their
mechanisms on diet-induced obesity, steatosis and insulin resistance.
Methods
Wild-type male C57BL6 mice were fed either normal or high fat diets. Some mice received
VSL#3 probiotics. Animal weight, hepatic steatosis, insulin resistance, and their
relationship to hepatic Natural Killer T cells (NKT) cell number and inflammatory
signaling were evaluated.
Results
High fat diet induced a depletion of hepatic NKT cells thus leading to insulin resistance
and steatosis. Oral probiotic treatment significantly improved the high fat diet-induced
hepatic NKT cell depletion, insulin resistance and hepatic steatosis. This effect
was NKT cell dependant, resulted from the attenuation of the tumor necrosis factor-alpha
and IκB kinase inflammatory signaling, and led to an improved sensitivity in insulin
signaling.
Conclusions
Probiotics improve high fat diet-induced steatosis and insulin resistance. These effects
of probiotics are likely due to increased hepatic NKT cell numbers and reduced inflammatory
signaling.
Keywords
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References
- Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001.JAMA. 2003; 289: 76-79
- Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey.JAMA. 2002; 287: 356-359
- The prevalence and etiology of elevated aminotransferase levels in the United States.Am J Gastroenterol. 2003; 98: 960-967
- Initiation of hyperinsulinemia and hyperleptinemia is diet dependant in C57BL/6 mice.Horm Metab Res. 1999; 31: 570-575
- Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: the KANWU Study.Diabetologia. 2001; 44: 312-319
- Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study.Aliment Pharmacol Ther. 2006; 23: 1143-1151
- Omega-3 fatty acids improve hepatic steatosis in a murine model: potential implications for the marginal steatotic liver donor.Transplantation. 2005; 79: 606-608
- Is type II diabetes mellitus a disease of the innate immune system?.Diabetologia. 1998; 41: 1241-1248
- Inflammatory status and insulin resistance.Curr Opin Clin Nutr Metab Care. 2002; 5: 551-559
- Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.Science. 1993; 259: 87-91
- Tumor necrosis factor alpha: a key component of the obesity-diabetes link.Diabetes. 1994; 43: 1271-1278
- Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB.Nat Med. 2005; 11: 183-190
- Conditional disruption of I{kappa}B kinase 2 fails to prevent obesity-induced insulin resistance.J Clin Invest. 2004; 113: 474-481
- The liver as a crucial orgain in the first line of host defense: the role of Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells and T helper 1 immune responses.Immunol Rev. 2000; 174: 35-46
- The gut microbiota as an environmental factor that regulates fat storage.PNAS. 2004; 101: 15718-15723
- An obesity-associated gut microbiome with increased capacity for energy harvest.Nature. 2006; 444: 1027
- Mechanisms underlying the resistance to diet-induced obesity in germ-free mice.PNAS. 2007; 104: 979-984
- Fuller R. Probiotics: the scientific basis. Chapman and Hall, London1992: 111-144
- Microbial ecology: human gut microbes associated with obesity.Nature. 2006; 444: 1022
- Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease.Hepatology. 2003; 37: 343-350
- Gut-liver axis: a new point of attack to treat chronic liver damage?.Am J Gastroenterol. 2002; 97: 2144-2146
- Dietary factors alter hepatic innate immune system in mice with nonalcoholic fatty liver disease.Hepatology. 2005; 42: 880-885
- A simple method for the isolation and purification of total lipids from animal tissues.J Biol Chem. 1957; 226: 457-509
- Fatty liver vulnerability to lipopolysaccharide despite NF-kB induction and caspase 3 inhibition.Am J Physiol. 2001; 281: G382-G392
- Single step method of RNA isolation by acid guanidine thiocyanate–phenol–chloroform extraction.Anal Biochem. 1987; 162: 156-161
- Recognition of bacterial glycosphingolipids by natural killer T cells.Nature. 2005; 434: 520-525
- Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections.Nature. 2005; 434: 525-529
- Specific detection of bifidobacterium strains in a pharmaceutical probiotic product and in human feces by polymerase chain reaction.Syst Appl Microbiol. 2000; 23: 391-399
- Impact on the composition of the faecal flora by a new probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis.Aliment Pharmacol Ther. 1999; 13: 1103-1108
- Amelioration of non-alcoholic steatohepatitis and glucose intolerance in ob/ob mice by oral immune regulation towards liver-extracted proteins is associated with elevated intrahepatic NKT lymphocytes and serum IL-10 levels.J Pathol. 2006; 208: 74-81
- CD1d1 mutant mice are deficient in natural T cells that promptly produce IL-4.Immunity. 1997; 6: 469-477
- NK T cell-induced protection against diabetes in V alpha 14-J alpha 281 transgenic nonobese diabetic mice is associated with a Th2 shift circumscribed regionally to the islets and functionally to islet autoantigen.J Immunol. 2001; 166: 3749-3756
- Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IKKbeta.Science. 2001; 293: 1673-1677
- Molecular mechanisms of insulin receptor substrate protein-mediated modulation of insulin signalling.FEBS Lett. 2003; 546: 32-36
- Insulin signalling and the regulation of glucose and lipid metabolism.Nature. 2001; 414: 799-806
- The methionine–choline deficient dietary model of steatohepatitis does not exhibit insulin resistance.J Hepatol. 2004; 40: 47-51
- Metabolic endotoxemia initiates obesity and insulin resistance.Diabetes. 2007; 56: 1761-1772
- Oral administration of butyrivibrio fibrisolvens, a butyrate-producing bacterium, decreases the formation of aberrant crypt foci in the colon and rectum of mice.J Nutr. 2005; 135: 2878-2883
- An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and humans.J Exp Med. 1994; 180: 1097-1106
- Insulin sensitivity and its measurement: structural commonalities among the methods.J Clin Endocrinol Metab. 2000; 85: 4426-4433
Article info
Publication history
Published online: July 01, 2008
Accepted:
May 29,
2008
Received in revised form:
May 14,
2008
Received:
February 18,
2008
Associate Editor: C.P. DayFootnotes
☆This work was supported by the American Gastroenterology Association Roche Research Scholar Award in Liver Diseases (Z.L.) and a research grant from NIH/NIDDK R01DK075990-01 (Z.L.)
Identification
Copyright
© 2008 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
