Impaired Hepatic Mitochondrial Capacity in Nonalcoholic Steatohepatitis Associated With Type 2 Diabetes.

Autor:	Gancheva S; Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich Heine University, Düsseldorf, Germany.; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany., Kahl S; Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich Heine University, Düsseldorf, Germany.; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany., Pesta D; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany., Mastrototaro L; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany., Dewidar B; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt., Strassburger K; German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany.; Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany., Sabah E; Obesity and Reflux Center, Neuwerk Hospital, Mönchengladbach, Germany., Esposito I; Institute of Pathology, Heinrich Heine University, Düsseldorf, Germany., Weiß J; German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany.; Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany., Sarabhai T; Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich Heine University, Düsseldorf, Germany.; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany., Wolkersdorfer M; Landesapotheke Salzburg, Salzburg, Austria., Fleming T; Department of Internal Medicine I, University Hospital Heidelberg, Heidelberg, Germany., Nawroth P; Department of Internal Medicine I, University Hospital Heidelberg, Heidelberg, Germany., Zimmermann M; Institute of Biochemistry and Molecular Biology I, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany., Reichert AS; Institute of Biochemistry and Molecular Biology I, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany., Schlensak M; Obesity and Reflux Center, Neuwerk Hospital, Mönchengladbach, Germany., Roden M; Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich Heine University, Düsseldorf, Germany.; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany.
Jazyk:	angličtina
Zdroj:	Diabetes care [Diabetes Care] 2022 Apr 01; Vol. 45 (4), pp. 928-937.
DOI:	10.2337/dc21-1758
Abstrakt:	Objective: Individuals with type 2 diabetes are at higher risk of progression of nonalcoholic fatty liver (steatosis) to steatohepatitis (NASH), fibrosis, and cirrhosis. The hepatic metabolism of obese individuals adapts by upregulation of mitochondrial capacity, which may be lost during the progression of steatosis. However, the role of type 2 diabetes with regard to hepatic mitochondrial function in NASH remains unclear. Research Design and Methods: We therefore examined obese individuals with histologically proven NASH without (OBE) (n = 30; BMI 52 ± 9 kg/m2) or with type 2 diabetes (T2D) (n = 15; 51 ± 7 kg/m2) as well as healthy individuals without liver disease (CON) (n = 14; 25 ± 2 kg/m2). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamps with d-[6,6-2H2]glucose. Liver biopsies were used for assessing mitochondrial capacity by high-resolution respirometry and protein expression. Results: T2D and OBE had comparable hepatic fat content, lobular inflammation, and fibrosis. Oxidative capacity in liver tissue normalized for citrate synthase activity was 59% greater in OBE than in CON, whereas T2D presented with 33% lower complex II-linked oxidative capacity than OBE and higher H2O2 production than CON. Interestingly, those with NASH and hepatic fibrosis score ≥1 had lower oxidative capacity and antioxidant defense than those without fibrosis. Conclusions: Loss of hepatic mitochondrial adaptation characterizes NASH and type 2 diabetes or hepatic fibrosis and may thereby favor accelerated disease progression. (© 2022 by the American Diabetes Association.)
Databáze:	MEDLINE
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