Effects of Caffeine and Chlorogenic Acid on Nonalcoholic Steatohepatitis in Mice Induced by Choline-Deficient, L-Amino Acid-Defined, High-Fat Diet.

Arisa Togashi-Kumagai,Yoshihisa Takahashi,Galtsog Lodon,Shiori Watabe,Ryoichi Yamaji,Toshio Fukusato,Yasuyuki Kobayashi,Masato Watanabe,Badamjav Sevjid,Naoki Harada,Erdenetsogt Dungubat

doi:10.3390/nu12123886

Abstract

Several recent experimental studies have investigated the effects of caffeine and chlorogenic acid (CGA), representative ingredients of coffee, on nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). However, the results are conflicting, and their effects are yet to be clarified. In the present study, we examined the effects of caffeine and CGA on choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-fed mice, relatively new model mice of NASH. Seven-week-old male C57BL/6J mice were divided into the following groups: Control diet (control), CDAHFD (CDAHFD), CDAHFD supplemented with 0.05% (w/w) caffeine (caffeine), and CDAHFD supplemented with 0.1% (w/w) CGA (CGA). After seven weeks, the mice were killed and serum biochemical, histopathological, and molecular analyses were performed. Serum alanine aminotransferase (ALT) levels were significantly higher in the caffeine and CGA groups than in the CDAHFD group. On image analysis, the prevalence of Oil red O-positive areas (reflecting steatosis) was significantly higher in the caffeine group than in the CDAHFD group, and that of CD45R-positive areas (reflecting lymphocytic infiltration) in the hepatic lobule was significantly higher in the caffeine and CGA groups than in the CDAHFD group. Hepatic expression of interleukin (IL)-6 mRNA was higher in the caffeine and CGA groups than in the CDAHFD group, and the difference was statistically significant for the caffeine group. In conclusion, in the present study, caffeine and CGA significantly worsened the markers of liver cell injury, inflammation, and/or steatosis in NASH lesions in mice.

Highlights

Nonalcoholic fatty liver disease (NAFLD) is defined as accumulation of excessive fat in the hepatocytes of patients without a history of large amount of alcohol drinking
Liver weight was significantly higher in the CDAHFD, caffeine, and chlorogenic acid (CGA) groups than in the control group (p = 0.003, p = 0.007, and p < 0.001, respectively)
The epididymal adipose tissue (EAT) weight was significantly lower in the CDAHFD, caffeine, and CGA groups than in the control group (p < 0.001 for all), and the EAT/body weight ratios were significantly lower in the CDAHFD, caffeine, and CGA

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is defined as accumulation of excessive fat in the hepatocytes of patients without a history of large amount of alcohol drinking. NAFLD includes a spectrum of liver diseases that ranges from simple steatosis (nonalcoholic fatty liver) to nonalcoholic steatohepatitis (NASH), which can progress to liver cirrhosis and hepatocellular carcinoma (HCC) [1,2,3]. NAFLD/NASH is rapidly increasing worldwide, in line with the increased prevalence of obesity because of lifestyle changes in recent years with the consumption of energy-rich diets. The prevalence of NAFLD in the general population of the world was estimated to be 25%, and the prevalence of NASH in the world was estimated to be 3–5% [4,5,6,7], demonstrating the importance of developing effective methods for their prevention and treatment. Coffee contains many physiologically active compounds [8,9]

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Discussion

Conclusion