Objective: Non-alcoholic fatty liver disease is characterized by high hepatic triacylglycerol contents, which is associated with endoplasmic reticulum (ER) stress and insulin resistance. Caffeic acid (CA) has antioxidant, immunomodulatory, and antiinflammatory effects. We investigated the effects of CA on hepatic steatosis and its mechanism of action. Methods: We treated CA (50 µM) with AML12 cells. We categorized mice into three groups as follows: low-fat diet mice (LFD, n = 10), high-fat diet-induced obese mice (HFD, n = 10), and HFD fed with CA (50 mg/kg/d, n = 10) for 10 wk. Results: CA did not cause any cytotoxic effect on AML12 cell line within the range of concentrations tested (0–200 µM). We found that CA (50 µM) treatment in palmitate-treated AML12 hepatocytes reduced lipid accumulation and lipogenesis markers, decreased ER stress, and increased autophagy markers. However, there was no significant difference in lipid droplets of palmitate-treated AML12 hepatocytes and CA-treated autophagy-related protein 7 deficiency AML12 hepatocytes with palmitate. Similarly, CA significantly lowered body and liver weights. Lipid accumulation in the liver decreased in the HFD + CA group compared with the HFD group. Glucose intolerance and insulin sensitivity also were markedly improved in the HFD + CA group. Moreover, the levels of ER stress markers were decreased in the livers of the HFD + CA group. Conclusion: Autophagy markers were increased in the livers of the HFD + CA group. These results suggest that caffeic acid may ameliorate hepatic steatosis and decrease ER stress by increasing autophagy.
Bibliographical noteFunding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2016 R1 A6 A3 A11933581).
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning ( NRF-2016 R1 A6 A3 A11933581 ).
© 2018 Elsevier Inc.
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Nutrition and Dietetics