Abstract
Obesity is associated with a cluster of metabolic disorders and systemic low-grade inflammation involving multiple organs. Recent findings have suggested that intestine is a key organ altered in response to high fat diet (HFD) feeding. Probiotics mainly lactobacillus strains have earlier been implicated in alleviating metabolic disorders. Here we aimed to examine the effects of a naturally occurring butyrate-producing probiotic clostridium butyricum CGMCC0313.1 (CB0313.1) in limiting the development of HFD-induced obesity. Mice treated with CB0313.1 exhibited reduced lipid accumulation in liver and serum, lower circulating insulin levels and improved glucose tolerance and insulin sensitivity. Furthermore, CB0313.1 administration reversed the HFD-induced colonic inflammation as evidenced by reduced tumor necrosis factor (TNF)-α level and increases the interleukin (IL)-10 and IL-22 levels in colon tissue. Additionally to colonic inflammation, CB0313.1 also reduced the colon permeability by upregulating the tight junction (TJ) proteins (claudin-1 and occludin) and contributed to a decreased circulating endotoxin level. In colon content, CB0313.1 administration restored the reduced production of butyrate and other short chain fatty acids (SCFAs) caused by HFD feeding. In adipose tissue, lower transcriptional levels of pro-inflammatory TNF-α, IL-6, IL-1β and monocyte chemotactic protein (MCP)-1 in adipose tissue were observed in CB0313.1-treated mice. Collectively, our data demonstrated that CB0313.1, targeting colon inflammation and permeability, ameliorated HFD-induced obesity, insulin resistance as well as adipose inflammation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipose Tissue / drug effects
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Adipose Tissue / immunology
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Adipose Tissue / metabolism
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Animals
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Chemokine CCL2 / genetics
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Chemokine CCL2 / immunology
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Claudin-1 / genetics
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Claudin-1 / immunology
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Clostridium butyricum / immunology*
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Colon / drug effects*
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Colon / immunology
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Colon / metabolism
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Diet, High-Fat / adverse effects
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Dietary Fats / administration & dosage
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Dietary Fats / adverse effects
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Endotoxins / blood
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Fatty Acids, Volatile / blood*
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Gene Expression Regulation
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Glucose Tolerance Test
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Homeostasis / drug effects
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Homeostasis / immunology
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Immunity, Innate
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Insulin / blood
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Insulin Resistance / immunology*
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Interleukin-10 / genetics
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Interleukin-10 / immunology
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Interleukin-22
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Interleukins / genetics
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Interleukins / immunology
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Liver / drug effects
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Liver / immunology
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Liver / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Obesity / diet therapy*
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Obesity / etiology
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Obesity / immunology
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Obesity / pathology
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Occludin / genetics
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Occludin / immunology
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Permeability
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Probiotics / pharmacology*
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Signal Transduction
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
Substances
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Ccl2 protein, mouse
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Chemokine CCL2
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Claudin-1
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Dietary Fats
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Endotoxins
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Fatty Acids, Volatile
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IL10 protein, mouse
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Insulin
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Interleukins
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Occludin
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Ocln protein, mouse
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Tumor Necrosis Factor-alpha
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Interleukin-10
Grants and funding
The present study was supported by funds from National Natural Science Foundation of China (grant NO.31471128) to YC. The present study was also supported from the National Natural Science Foundation of China (grant nos. 31400779 and 31570915; National Young 1000 Talents Plan), the Provincial Natural Science Foundation of Jiangsu (grant NO. BK20130133), Jiangsu Province Recruitment Plan for High-level, Innovative and Entrepreneurial Talents, Jiangsu Province ‘Six Summit Talents’ Program (grant NO. 2014-SWYY-035) and Key Program of Fundamental Research Funds for the Central Universities (grant NO. JUSRP51613A) to JS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.