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Impaired hepatic mitochondrial capacity in nonalcoholic steatohepatitis associated with Type 2 diabetes

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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 ste...

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Main Authors: Gancheva, Sofiya (Author) , Kahl, Sabine (Author) , Pesta, Dominik (Author) , Mastrototaro, Lucia (Author) , Dewidar, Bedair (Author) , Strassburger, Klaus (Author) , Sabah, Ehsan (Author) , Esposito, Irene (Author) , Weiß, Jürgen (Author) , Sarabhai, Theresia (Author) , Wolkersdorfer, Martin (Author) , Fleming, Thomas (Author) , Nawroth, Peter Paul (Author) , Zimmermann, Marcel (Author) , Reichert, Andreas S. (Author) , Schlensak, Matthias (Author) , Roden, Michael (Author)
Format: Article (Journal)
Language:English
Published: February 03 2022
In: Diabetes care
Year: 2022, Volume: 45, Issue: 4, Pages: 928-937
ISSN:1935-5548
DOI:10.2337/dc21-1758
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.2337/dc21-1758
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Author Notes:Sofiya Gancheva, Sabine Kahl, Dominik Pesta, Lucia Mastrototaro, Bedair Dewidar, Klaus Strassburger, Ehsan Sabah, Irene Esposito, Jürgen Weiß, Theresia Sarabhai, Martin Wolkersdorfer, Thomas Fleming, Peter Nawroth, Marcel Zimmermann, Andreas S. Reichert, Matthias Schlensak and Michael Roden
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Summary: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.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.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.Loss of hepatic mitochondrial adaptation characterizes NASH and type 2 diabetes or hepatic fibrosis and may thereby favor accelerated disease progression.
Item Description:Gesehen am 15.09.2022
Physical Description:Online Resource
ISSN:1935-5548
DOI:10.2337/dc21-1758

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