L-carnitine ameliorated fatty liver in high-calorie diet/STZ-induced type 2 diabetic mice by improving mitochondrial function - PubMed (original) (raw)

L-carnitine ameliorated fatty liver in high-calorie diet/STZ-induced type 2 diabetic mice by improving mitochondrial function

Yunqiu Xia et al. Diabetol Metab Syndr. 2011.

Abstract

Background: There are an increasing number of patients suffering from fatty liver caused by type 2 diabetes. We intended to study the preventive and therapeutic effect of L-carnitine (LC) on nonalcoholic fatty liver disease (NAFLD) in streptozotocin (STZ)-induced type 2 diabetic mice and to explore its possible mechanism.

Methods: Thirty male Kungming mice were randomly divided into five groups: control group, diabetic group, pre-treatment group (125 mg/kg BW), low-dose (125 mg/kg BW) therapeutic group and high-dose (250 mg/kg BW) therapeutic group. The morphology of hepatocytes was observed by light and electron microscopy. LC and ALC (acetyl L-carnitine) concentrations in the liver were determined by high-performance liquid chromatography (HPLC). Moreover, liver weight, insulin levels and free fatty acid (FFA) and triglyceride (TG) levels in the liver and plasma were measured.

Results: Average liver LC and ALC levels were 33.7% and 20% lower, respectively, in diabetic mice compared to control mice (P < 0.05). After preventive and therapeutic treatment with LC, less hepatocyte steatosis, clearer crista and fewer glycogen granules in the mitochondria were observed. Decreased liver weight, TG levels, and FFA concentrations (P < 0.05) in the liver were also observed after treatment with LC in diabetic mice. Moreover, liver LC and ALC levels increased upon treatment with LC, whereas the ratio of LC and ALC decreased significantly (P < 0.01).

Conclusion: LC supplements ameliorated fatty liver in type 2 diabetic mice by increasing fatty acid oxidation and decreasing the LC/ALC ratio in the liver. Therefore, oral administration of LC protected mitochondrial function in liver.

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Figures

Figure 1

Figure 1

Effects of LC on the changes in body weights of STZ-treated mice. control: control group (n = 6), DM+NS: diabetic group (n = 4), pre-treatment: preventive group (n = 3), DM+LC (H): high-dose therapeutic group (n = 4), DM+LC (L): low-dose therapeutic group (n = 3). All values are expressed as the mean ± S.E. using the repeated measures method. *P < 0.05, **P < 0.01 (compared to control group), #P < 0.05, ##P < 0.01 (compared to diabetic group).

Figure 2

Figure 2

LC's effect on liver sections stained by oil red O (×100 times). a, Oil red O images A. control group, B. diabetic group, C. preventive group, D. high-dose therapeutic group, E. low-dose therapeutic group. Red points in the image indicate lipid droplets stained by oil red O. b, Lipid profile area percentage Control+NS: control group (n = 3), DM+NS: diabetic group (n = 5), pre-treat: preventive group (n = 5), DM+LC (H): high-dose therapeutic group (n = 3), DM+LC (L): low-dose therapeutic group (n = 6). All values are expressed as the mean ± S.E. using the repeated measures method. **P < 0.01 (compared to control group), ##P < 0.01 (compared to diabetic group).

Figure 3

Figure 3

Effect of LC on the liver by electron microscopy (×30K). A. control group, B. diabetic group, C. preventive group, D. high-dose therapeutic group, E. low-dose therapeutic group. Mitochondrial (→), glycogen granules (↓), rough endoplasmic reticulum (←)

Figure 4

Figure 4

Effect of LC on lipid metabolism in the liver and peripheral adipocytes in STZ-treated mice. Acyl-CoA: long chain acyl CoA, CPT-1: carnitine palmitoyltransferase-1, CAT: carnitine/acylcarnitine translocase, HSL: hormone-sensitive lipase.

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