Helicobacter pylori Colonization Ameliorates Glucose Homeostasis in Mice through a PPAR γ-Dependent Mechanism

被引:31
作者
Bassaganya-Riera, Josep [1 ,4 ]
Dominguez-Bello, Maria Gloria [2 ]
Kronsteiner, Barbara [1 ]
Carbo, Adria [1 ]
Lu, Pinyi [1 ]
Viladomiu, Monica [1 ]
Pedragosa, Mireia [1 ]
Zhang, Xiaoying [1 ]
Sobral, Bruno W. [1 ]
Mane, Shrinivasrao P. [1 ]
Mohapatra, Saroj K. [1 ]
Horne, William T. [1 ]
Guri, Amir J. [1 ]
Groeschl, Michael [3 ]
Lopez-Velasco, Gabriela [1 ]
Hontecillas, Raquel [1 ]
机构
[1] Virginia Tech, Nutr Immunol & Mol Med Lab, Ctr Modeling Immun Enter Pathogens, Virginia Bioinformat Inst, Blacksburg, VA USA
[2] Univ Puerto Rico, Dept Biol, San Juan, PR 00936 USA
[3] Univ Erlangen Nurnberg, D-91054 Erlangen, Germany
[4] Virginia Tech, Dept Biomed Sci & Pathobiol, VA MD Reg Coll Vet Med, Blacksburg, VA USA
来源
PLOS ONE | 2012年 / 7卷 / 11期
基金
美国国家卫生研究院;
关键词
CONJUGATED LINOLEIC-ACID; HOMOTYPIC PHAGOSOME FUSION; INSULIN-RESISTANCE; ADIPOSE-TISSUE; CAGA(-) STRAINS; INFECTION; INFLAMMATION; OBESITY; LEPTIN; GHRELIN;
D O I
10.1371/journal.pone.0050069
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: There is an inverse secular trend between the incidence of obesity and gastric colonization with Helicobacter pylori, a bacterium that can affect the secretion of gastric hormones that relate to energy homeostasis. H. pylori strains that carry the cag pathogenicity island (PAI) interact more intimately with gastric epithelial cells and trigger more extensive host responses than cag(-) strains. We hypothesized that gastric colonization with H. pylori strains differing in cag PAI status exert distinct effects on metabolic and inflammatory phenotypes. Methodology/Principal Findings: To test this hypothesis, we examined metabolic and inflammatory markers in db/db mice and mice with diet-induced obesity experimentally infected with isogenic forms of H. pylori strain 26695: the cag PAI wild-type and its cag PAI mutant strain 99-305. H. pylori colonization decreased fasting blood glucose levels, increased levels of leptin, improved glucose tolerance, and suppressed weight gain. A response found in both wild-type and mutant H. pylori strain-infected mice included decreased white adipose tissue macrophages (ATM) and increased adipose tissue regulatory T cells (Treg) cells. Gene expression analyses demonstrated upregulation of gastric PPAR gamma-responsive genes (i.e., CD36 and FABP4) in H. pylori-infected mice. The loss of PPAR gamma in immune and epithelial cells in mice impaired the ability of H. pylori to favorably modulate glucose homeostasis and ATM infiltration during high fat feeding. Conclusions/Significance: Gastric infection with some commensal strains of H. pylori ameliorates glucose homeostasis in mice through a PPAR gamma-dependent mechanism and modulates macrophage and Treg cell infiltration into the abdominal white adipose tissue.
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页数:10
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