Korean J Gastroenterol.  2010 Jun;55(6):384-389. 10.4166/kjg.2010.55.6.384.

Effects of Carnitine on Peripheral Blood Mitochondrial DNA Copy Number and Liver Function in Non-Alcoholic Fatty Liver Disease

• Lim CY
• Jun DW
• Jang SS
• Cho WK
• Chae JD
• Jun JH

• KMID: 948767
• DOI: http://doi.org/10.4166/kjg.2010.55.6.384

Abstract

BACKGROUND/AIMS
Functional and anatomical abnormalities of mitochondria play an important role in developing steatohepatitis. Carnitine is essential for enhanced mitochondrial beta oxidation through the transfer of long-chain fatty acids into the mitochondria. We examined the impact of carnitine complex on liver function and peripheral blood mitochondria copy number in NAFLD patients.
METHODS
Forty-five NAFLD patients were enrolled. Patients were categorized into the carnitine complex-administered group and control group. Before and 3 months after drug administration, a liver function test and peripheral blood mitochondrial DNA and 8-oxo-dG quantitive analysis were conducted.
RESULTS
In carnitine treatment group, ALT, AST, and total bilirubin were reduced after medication. There was no difference in AST, ALT, and total bilirubin between before and after treatment in control group. In carnitine group, peripheral mitochondrial DNA copy number was significantly increased from 158.8+/-69.5 copy to 241.6+/-180.6 copy (p=0.025). While in control group the mitochondrial copy number was slightly reduced from 205.5+/-142.3 to 150.0+/-109.7. 8-oxo-dG level was also tended to decrease in carnitine group (p=0.23) and tended to increase in control group (p=0.07).
CONCLUSIONS
In NAFLD, the carnitine improved liver profile and peripheral blood mitochondrial DNA copy number. This results suggest that carnitine activate the mitochondria, thereby contributing to the improvement of NAFLD.

Keyword

Nonalcholic fatty liver disease; Mitochondria; Carnitine

MeSH Terms

Adult
Aged
Alanine Transaminase/blood
Aspartate Aminotransferases/blood
Bilirubin/blood
Carnitine/*therapeutic use
DNA Copy Number Variations/*drug effects
DNA, Mitochondrial/*blood
Deoxyguanosine/analogs &derivatives/analysis
Fatty Liver/diagnosis/*drug therapy/genetics
Female
Humans
Liver Function Tests
Male
Middle Aged

Figure

• 

  Fig. 1. Changes of liver chemistry between values at baseline and 3 month in the same group. Grey bar, before medication; Black bar, after medication. (A) Aspartic acid transaminase, (B) Alanine transaminase, (C) Bilirubin, (D) γ-GTP. ∗ p<0.05 by paired t-test.

• 

  Fig. 2. Changes of mitochondrial DNA copy number before and after medication in both groups. Grey bar, before medication; Black bar, after medication. ∗ p＜0.05 by paired t-test.

• 

  Fig. 3. Difference of 8-oxo-dG before and after medication in both groups.

• 

  Fig. 4. Peripheral blood mitochondria DNA copy number between biopsy proven steatosis and steatohepatitis.

Reference

1. Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology. 2002; 122:1649–1657.

2. Pessayre D, Fromenty B. NASH: a mitochondrial disease. J Hepatol. 2005; 42:928–940.

3. Berson A, De Beco V, Letté ron P, et al. Steatohepatitis-in-ducing drugs cause mitochondrial dysfunction and lipid per-oxidation in rat hepatocytes. Gastroenterology. 1998; 114:764–774.

4. Ibdah JA, Perlegas P, Zhao Y, et al. Mice heterozygous for a defect in mitochondrial trifunctional protein develop hepatic steatosis and insulin resistance. Gastroenterology. 2005; 128:1381–1390.

5. Pé rez-Carreras M, Del Hoyo P, Martí n MA, et al. Defective hepatic mitochondrial respiratory chain in patients with non-alcoholic steatohepatitis. Hepatology. 2003; 38:999–1007.

6. Song J, Oh JY, Sung YA, Pak YK, Park KS, Lee HK. Peripheral blood mitochondrial DNA content is related to insulin sensitivity in offspring of type 2 diabetic patients. Diabetes Care. 2001; 24:865–869.

7. Lee HK, Song JH, Shin CS, et al. Decreased mitochondrial DNA content in peripheral blood precedes the development of non-insulindependent diabetes mellitus. Diabetes Res Clin Pract. 1998; 42:161–167.

8. Wu X, Zhang L, Gurley E, et al. Prevention of free fatty acid-induced hepatic lipotoxicity by 18beta-glycyrrhetinic acid through lysosomal and mitochondrial pathways. Hepatology. 2008; 47:1905–1915.

9. Szeto HH. Mitochondria-targeted peptide antioxidants: novel neuroprotective agents. AAPS J. 2006; 8:E521–531.

10. Bremer J. Carnitine–metabolism and functions. Physiol Rev. 1983; 63:1420–1480.

11. Bowyer BA, Miles JM, Haymond MW, Fleming CR. L-carni-tine therapy in home parenteral nutrition patients with abnormal liver tests and low plasma carnitine concentrations. Gastroenterology. 1988; 94:434–438.

12. Krä henbü hl S, Mang G, Kupferschmidt H, Meier PJ, Krause M. Plasma and hepatic carnitine and coenzyme A pools in a patient with fatal, valproate induced hepatotoxicity. Gut. 1995; 37:140–143.

13. Romano M, Vacante M, Cristaldi E, et al. L-carnitine treatment reduces steatosis in patients with chronic hepatitis C treated with alpha-interferon and ribavirin. Dig Dis Sci. 2008; 53:1114–1121.

14. Kumaran S, Subathra M, Balu M, Panneerselvam C. Supplementation of L-carnitine improves mitochondrial enzymes in heart and skeletal muscle of aged rats. Exp Aging Res. 2005; 31:55–67.

15. Kraemer WJ, Volek JS, French DN, et al. The effects of L-carnitine L-tartrate supplementation on hormonal responses to resistance exercise and recovery. J Strength Cond Res. 2003; 17:455–462.