The Protective Effect of Cynara Cardunculus Extract in Diet-Induced NAFLD: Involvement of OCTN1 and OCTN2 Transporter Subfamily

Abstract

Hyperlipidemia and insulin-resistance are often associated with Non-Alcoholic Fatty Liver Disease (NAFLD) thereby representing a true issue worldwide due to increased risk of developing cardiovascular and systemic disorders. Although clear evidence suggests that circulating fatty acids contribute to pathophysiological mechanisms underlying NAFLD and hyperlipidemia, further studies are required to better identify potential beneficial approaches for counteracting such a disease. Recently, several artichoke extracts have been used for both reducing hyperlipidemia, insulin-resistance and NAFLD, though the mechanism is unclear. Here we used a wild type of Cynara Cardunculus extract (CyC), rich in sesquiterpens and antioxidant active ingredients, in rats fed a High Fat Diet (HFD) compared to a Normal Fat Diet (NFD). In particular, in rats fed HFD for four consecutive weeks, we found a significant increase of serum cholesterol, triglyceride and serum glucose. This effect was accompanied by increased body weight and by histopathological features of liver steatosis. The alterations of metabolic parameters found in HFDs were antagonised dose-dependently by daily oral supplementation of rats with CyC 10 and 20 mg/kg over four weeks, an effect associated to significant improvement of liver steatosis. The effect of CyC (20 mg/kg) was also associated to enhanced expression of both OCTN1 and OCTN2 carnitine-linked transporters. Thus, present data suggest a contribution of carnitine system in the protective effect of CyC in diet-induced hyperlipidemia, insulin-resistance and NAFLD.

Keywords: Non-Alcoholic Fatty Liver Disease (NAFLD); OCTN1; OCTN2; hyperlipidemia; insulin-resistance.

Figure 1

Study design.

Figure 2

The effect of CyC (10 and 20 mg/kg daily given orally over a period of four weeks) on body weight in Normal Fat Diet (NFD) and High Fat Diet (HFD) groups. Data are expressed as mean ± SE.* P < 0.05 HFD vs. NFD. ^§ P < 0.05 HFD + CyC vs. HFD.

Figure 3

The effect of CyC (10 and 20 mg/kg given daily and orally over a period of four weeks) on histopathological features of liver steatosis in NFD and HFD. Histopathological sections have been stained with hematoxylin-eosin.

Figure 4

The effect of CyC (10 and 20 mg/kg daily given orally over a period of four weeks) on OCTN1 (A,B) and OCTN2 (C,D) carnitine-linked transporters in NFD and HFD. Representative Western blotting analysis are expressed in subgraph A and C. Optical Density for each blot is expressed in Subgraph B and D). Data are expressed as mean ± SE.* P < 0.05 HFd vs. NFD. ^§ P < 0.05 HFD + CyC vs. HFD.