Nonalcoholic steatohepatitis (NASH) has multiple etiologic associations, but the pathogenesis is poorly understood. Cytochrome P450 (CYP) 2E1 is induced in the liver of patients who drink alcohol to excess and is important in the pathogenesis of alcoholic liver disease (ALD). We have previously show
Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis
✍ Scribed by Mercedes Pérez-Carreras; Pilar Del Hoyo; Miguel A. Martín; Juan C. Rubio; Ana Martín; Gregorio Castellano; Francisco Colina; Joaquín Arenas; José A. Solis-Herruzo
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 994 KB
- Volume
- 38
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Mitochondrial dysfunction might play a central role in the pathogenesis of nonalcoholic steatohepatitis (NASH). The aims of this study were to evaluate whether free fatty acid (FFA) transport into the mitochondria or the activity of mitochondria respiratory chain (MRC) complexes are impaired in NASH. In patients with NASH and control subjects, we measured free carnitine, short-chain acylcarnitine (SCAC) and long-chain acylcarnitine (LCAC) esters, carnitine palmitoyltransferase (CPT) activity, and MRC enzyme activity in liver tissue as well as serum concentration of tumor necrosis factor a (TNF-a), homeostatic metabolic assessment of insulin resistance (HOMAIR), and body mass index (BMI). In patients with NASH, the LCAC/free carnitine ratio was significantly increased and the SCACIfree carnitine ratio was decreased. In patients with NASH, the activity of the MRC complexes was decreased to 63% f 20% (complex I), 58.5% f 16.7% (complex 11), 70.6% 2 10.3% (complex TII), 62.5% f 13% (complex IV), and 42.4% f 9.1% (adenosine triphosphate synthase) of the corresponding control values. Activity of these complexes correlated significantly with serum TNF-a and HOMAIR. Serum TNF-a (36.3 f 23.1 pg/mL), HOMAIR (4.5 f 2.38), and BMI (29.9 2 3.5 kg/m2) values were significantly increased in patients with NASH. In conclusion, activities of MRC complexes were decreased in liver tissue of patients with NASH. This dysfunction correlated with serum TNF-a, insulin resistance, and BMI values. (HEPATOLOGY 2003;38:999-1007.) N onalcoholic steatohepatitis (NASH) is a clinicopathologic condition characterized by histologic features of alcoholic liver disease that occurs in patients who do not consume significant amounts of alcohol.' At this moment, NASH is considered part of a large spectrum of nonalcoholic fatty liver disease that also includes pure fatty liver (hepatic steatosis), hepatic steato-
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