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Chlorogenic Acid Improves High Fat Diet-Induced Hepatic Steatosis and Insulin Resistance in Mice

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ABSTRACT

Purpose

Chlorogenic acid (CGA), the most abundant component in coffee, has exhibited many biological activities. The objective of this study is to assess preventive and therapeutic effects of CGA on obesity and obesity-related liver steatosis and insulin resistance.

Methods

Two sets of experiments were conducted. In set 1, 6-week old C57BL/6 mice were fed a regular chow or high-fat diet (HFD) for 15 weeks with twice intra-peritoneal (IP) injection of CGA (100 mg/kg) or DMSO (carrier solution) per week. In set 2, obese mice (average 50 g) were treated by CGA (100 mg/kg, IP, twice weekly) or DMSO for 6 weeks. Body weight, body composition and food intake were monitored. Blood glucose, insulin and lipid levels were measured at end of the study. Hepatic lipid accumulation and glucose homeostasis were evaluated. Additionally, genes involved in lipid metabolism and inflammation were analyzed by real time PCR.

Results

CGA significantly blocked the development of diet-induced obesity but did not affect body weight in obese mice. CGA treatment curbed HFD-induced hepatic steatosis and insulin resistance. Quantitative PCR analysis shows that CGA treatment suppressed hepatic expression of Pparγ, Cd36, Fabp4, and Mgat1 gene. CGA treatment also attenuated inflammation in the liver and white adipose tissue accompanied by a decrease in mRNA levels of macrophage marker genes including F4/80, Cd68, Cd11b, Cd11c, and Tnfα, Mcp-1 and Ccr2 encoding inflammatory proteins.

Conclusion

Our study provides direct evidence in support of CGA as a potent compound in preventing diet-induced obesity and obesity-related metabolic syndrome. Our results suggest that drinking coffee is beneficial in maintaining metabolic homeostasis when on a high fat diet.

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported in part by the National Institute of Health (RO1EB007357 and RO1HL098295). We thank Ms. Ryan Fugett for proof-reading and English editing.

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Authors and Affiliations

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

    Yongjie Ma, Mingming Gao & Dexi Liu

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  1. Yongjie Ma
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Correspondence to Dexi Liu.

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Ma, Y., Gao, M. & Liu, D. Chlorogenic Acid Improves High Fat Diet-Induced Hepatic Steatosis and Insulin Resistance in Mice. Pharm Res 32, 1200–1209 (2015). https://doi.org/10.1007/s11095-014-1526-9

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  • DOI: https://doi.org/10.1007/s11095-014-1526-9

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