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Rutin Suppresses Palmitic Acids-Triggered Inflammation in Macrophages and Blocks High Fat Diet-Induced Obesity and Fatty Liver in Mice

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Abstract

Purpose

To elucidate the mechanism of rutin in blocking macrophage-mediated inflammation and high fat diet-induced obesity and fatty liver.

Methods

Both in vitro and in vivo approaches were taken in evaluating the effects of rutin on palmitic acids-triggered inflammation in cultured macrophages, and on weight gain and development of fatty liver of mice fed a high fat diet.

Results

Palmitic acids increase mRNA levels of pro-inflammatory cytokines, and elevate the production of TNFα in cultured macrophages. Pre-exposure of rutin to cells greatly suppressed these elevations. The suppressed inflammation by rutin was correlated with a decrease in transcription of genes responsible for ER stress and production of reactive oxygen species. In vivo, rutin protects mice from high fat diet-induced obesity, fatty liver and insulin resistance. The protective effects were associated with lack of hypertrophy and crown-like structures in the white adipose tissue, decreased mRNA levels of marker genes for macrophages including F4/80, Cd11c and Cd68, and repressed transcription of genes involved in chronic inflammation such as Mcp1 and Tnfα in white adipose tissue. In addition, rutin increases the expression of genes responsible for energy expenditure in brown adipose tissue including Pgc1α and Dio2. Furthermore, rutin suppresses transcription of Srebp1c and Cd36 in the liver, leading to a blockade of fatty liver development.

Conclusion

These results suggest that supplementation of rutin is a promising strategy for blocking macrophage-mediated inflammation and inflammation-induced obesity and its associated complications.

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Acknowledgments And Disclosures

The study was supported in part by grants from NIH (RO1EB007357 and RO1HL098295). We thank Ms. Ryan Fugett for English editing. The authors claim no conflicts of interest.

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Authors and Affiliations

  1. Department of Pharmaceutical and Biomedical Sciences College of Pharmacy, University of Georgia, 450 Pharmacy South 250 West Green Street, Athens, Georgia, 30602, USA

    Mingming Gao, Yongjie Ma & Dexi Liu

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  1. Mingming Gao
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  2. Yongjie Ma
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  3. Dexi Liu
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Correspondence to Dexi Liu.

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Gao, M., Ma, Y. & Liu, D. Rutin Suppresses Palmitic Acids-Triggered Inflammation in Macrophages and Blocks High Fat Diet-Induced Obesity and Fatty Liver in Mice. Pharm Res 30, 2940–2950 (2013). https://doi.org/10.1007/s11095-013-1125-1

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  • DOI: https://doi.org/10.1007/s11095-013-1125-1

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