Coenzyme Q metabolism is disturbed in high fat diet-induced non-alcoholic fatty liver disease in rats

Elena Bravo, Simonetta Palleschi, Barbara Rossi, Mariarosaria Napolitano, Luca Tiano, Emanuela D'Amore, Kathleen M Botham, Elena Bravo, Simonetta Palleschi, Barbara Rossi, Mariarosaria Napolitano, Luca Tiano, Emanuela D'Amore, Kathleen M Botham

Abstract

Oxidative stress is believed to be a major contributory factor in the development of non alcoholic fatty liver disease (NAFLD), the most common liver disorder worldwide. In this study, the effects of high fat diet-induced NAFLD on Coenzyme Q (CoQ) metabolism and plasma oxidative stress markers in rats were investigated. Rats were fed a standard low fat diet (control) or a high fat diet (57% metabolizable energy as fat) for 18 weeks. The concentrations of total (reduced + oxidized) CoQ9 were increased by >2 fold in the plasma of animals fed the high fat diet, while those of total CoQ10 were unchanged. Reduced CoQ levels were raised, but oxidized CoQ levels were not, thus the proportion in the reduced form was increased by about 75%. A higher percentage of plasma CoQ9 as compared to CoQ10 was in the reduced form in both control and high fat fed rats. Plasma protein thiol (SH) levels were decreased in the high fat-fed rats as compared to the control group, but concentrations of lipid hydroperoxides and low density lipoprotein (LDL) conjugated dienes were unchanged. These results indicate that high fat diet-induced NAFLD in rats is associated with altered CoQ metabolism and increased protein, but not lipid, oxidative stress.

Keywords: Coenzyme Q; antioxidants; non alcoholic fatty liver disease; oxidative stress; protein thiol groups; rats.

Figures

Figure 1
Figure 1
Rats were fed standard low fat diet (Control diet) or a high fat diet for 18 weeks. Blood samples were then collected and the concentrations of triacylglycerol (TG) (A) and total cholesterol (TC) (B), total lipids (TG + TC) (C) and insulin (D) in plasma were determined and the Homeostatic model assessment of insulin resistance (HOMA-IR) (E) was calculated. Data are the mean from 7 (Control diet) or 10 (High fat diet) animals and error bars show the SEM. ** P < 0.01, *** P < 0.001 vs. Control diet.
Figure 2
Figure 2
Rats were fed standard low fat diet (Control diet) or a high fat diet for 18 weeks. Livers were collected and sections were stained with haematoxylin-eosin (H&E). (A) Control diet; (B) High fat diet. Images typical of sections taken from 7 rats fed the control diet and 10 rats fed the high fat diet are shown. Original magnification 40×.
Figure 3
Figure 3
Plasma Coenzyme Q (CoQ) levels in rats fed a standard low fat (Control diet) or a high fat diet for 18 weeks. Blood samples were collected and the concentrations of reduced (RedCoQ) and oxidised (OxCoQ) CoQ9 and CoQ10 in plasma were determined. Total CoQ values are RedCoQ + OxCoQ. (A) CoQ (CoQ9 + CoQ10) and RedCoQ/OxCoQ; (B) CoQ9 and RedCoQ9/OxCoQ9; (C) CoQ10 and RedCoQ10/ OxCoQ10; Data are the mean from 6 (Control diet) or 10 (High fat diet) animals and error bars show the SEM. * P < 0.05, ** P < 0.01, *** P < 0.001 vs. Control diet.
Figure 3
Figure 3
Plasma Coenzyme Q (CoQ) levels in rats fed a standard low fat (Control diet) or a high fat diet for 18 weeks. Blood samples were collected and the concentrations of reduced (RedCoQ) and oxidised (OxCoQ) CoQ9 and CoQ10 in plasma were determined. Total CoQ values are RedCoQ + OxCoQ. (A) CoQ (CoQ9 + CoQ10) and RedCoQ/OxCoQ; (B) CoQ9 and RedCoQ9/OxCoQ9; (C) CoQ10 and RedCoQ10/ OxCoQ10; Data are the mean from 6 (Control diet) or 10 (High fat diet) animals and error bars show the SEM. * P < 0.05, ** P < 0.01, *** P < 0.001 vs. Control diet.
Figure 4
Figure 4
Plasma CoQ9:CoQ10 ratios in rats fed a standard low fat (Control diet) or a high fat diet for 18 weeks. Blood samples were collected and the concentrations of reduced (RedCoQ) and oxidised (OxCoQ) CoQ9 and CoQ10 in plasma were measured and the ratio of CoQ9:CoQ10 was calculated. Data are the mean from 6 (Control diet) or 10 (High fat diet) animals and error bars show the SEM. ** P < 0.01, *** P < 0.001 vs. Control diet.
Figure 5
Figure 5
Blood oxidative stress markers in rats fed a standard low fat (Control diet) or a high fat diet for 18 weeks. Blood samples were collected and the plasma or LDL (conjugated dienes formation in response to copper oxidation) content of (A) protein thiol (SH) groups; (B) conjugated dienes (Vmax × 103 of propagation phase, determined using 50 μg/mL LDL protein); (C) reactive oxygen species (dROMs) was determined. (D) dROMs/plasma lipids. Data are the mean from 6 (control diet) or 9 (High fat diet) animals (protein SH groups and dROMs). For conjugated dienes the mean of 5 rats in each group are shown. Error bars show the SEM. ** P < 0.01, *** P < 0.001 vs. Control diet.
Figure 6
Figure 6
Plasma antioxidant levels in rats fed a standard low fat (Control diet) or a high fat diet for 18 weeks. Blood samples were collected and the concentrations of (A) Red blood cell glutathione (GSH) (data expressed as μmol/mL whole blood); (B) VitA; and (C) VitE were determined. (D) VitE/plasma lipids (μmol/mmol). Data for GSH are the mean from 7 (Control diet) or 9 (High fat diet) animals and those for vitamins A and E are the mean from 4 (control diet) or 6 (High fat diet) rats. Error bars show the SEM. ** P < 0.01 vs. Control diet.

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