Universität zu Köln

Pafili, Kalliopi ORCID: 0000-0003-4293-3514, Kahl, Sabine, Mastrototaro, Lucia, Strassburger, Klaus, Pesta, Dominik ORCID: 0000-0002-5089-3586, Herder, Christian, Putzer, Jennifer, Dewidar, Bedair, Hendlinger, Mona, Granata, Cesare, Saatmann, Nina, Yavas, Aslihan ORCID: 0000-0002-8408-3063, Gancheva, Sofiya, Heilmann, Geronimo, Esposito, Irene, Schlensak, Matthias and Roden, Michael (2022). Mitochondrial respiration is decreased in visceral but not subcutaneous adipose tissue in obese individuals with fatty liver disease. J. Hepatol., 77 (6). S. 1504 - 1516. AMSTERDAM: ELSEVIER. ISSN 1600-0641

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Abstract

Background & Aims: Adipose tissue dysfunction is involved in the development of insulin resistance and is responsible for excessive lipid delivery to other organs such as the liver. We tested the hypothesis that impaired mitochondrial function is a common feature of subcutaneous (SAT) and visceral adipose tissue (VAT), but may differently contribute to adipose tissue insulin resistance (IR) in obesity, non-alcoholic fatty liver (NAFL) and steatohepatitis (NASH). Methods: In this cross-sectional study, we analyzed tissuespecific insulin sensitivity using stable isotope dilution and hyperinsulinemic-normoglycemic clamp tests. We also assessed mitochondrial respiration, mRNA and protein expression, and tissue morphology in biopsies of SAT and VAT from obese humans without NAFL, with NAFL or with NASH (n = 22/group). Results: Compared to individuals without liver disease, persons with NAFL and NASH had about 30% (p = 0.010) and 33% (p = 0.002) lower maximal mitochondrial respiration, respectively, in VAT, but not in SAT. The lower maximal mitochondrial respiration of VAT was associated with lower adipose tissue insulin sensitivity (b = 0.985, p = 0.041) and with increased VAT protein expression of tumor necrosis factor A across all groups (b = -0.085, p = 0.040). VAT from individuals with NASH was characterized by lower expression of oxidative phosphorylation complex IV (p = 0.042) and higher mRNA expression of the macrophage marker CD68 (p = 0.002) than VAT from participants without NAFL. Conclusions: Humans with non-alcoholic fatty liver disease have distinct abnormalities of VAT energy metabolism, which correlate with adipose tissue dysfunction and may favor progression of NAFL to NASH. Lay summary: Adipose tissue (commonly called body fat) can be found under the skin (subcutaneous) or around internal organs (visceral). Dysfunction of adipose tissue can cause insulin resistance and lead to excess delivery of fat to other organs such as the liver. Herein, we show that dysfunction specifically in visceral adipose tissue was associated with fatty liver disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pafili, Kalliopi UNSPECIFIED orcid.org/0000-0003-4293-3514 UNSPECIFIED Kahl, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Mastrototaro, Lucia UNSPECIFIED UNSPECIFIED UNSPECIFIED Strassburger, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Pesta, Dominik UNSPECIFIED orcid.org/0000-0002-5089-3586 UNSPECIFIED Herder, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Putzer, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED Dewidar, Bedair UNSPECIFIED UNSPECIFIED UNSPECIFIED Hendlinger, Mona UNSPECIFIED UNSPECIFIED UNSPECIFIED Granata, Cesare UNSPECIFIED UNSPECIFIED UNSPECIFIED Saatmann, Nina UNSPECIFIED UNSPECIFIED UNSPECIFIED Yavas, Aslihan UNSPECIFIED orcid.org/0000-0002-8408-3063 UNSPECIFIED Gancheva, Sofiya UNSPECIFIED UNSPECIFIED UNSPECIFIED Heilmann, Geronimo UNSPECIFIED UNSPECIFIED UNSPECIFIED Esposito, Irene UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlensak, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Roden, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-687696
DOI:	10.1016/j.jhep.2022.08.010
Journal or Publication Title:	J. Hepatol.
Volume:	77
Number:	6
Page Range:	S. 1504 - 1516
Date:	2022
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1600-0641
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEPATIC INSULIN-RESISTANCE Multiple languages Gastroenterology & Hepatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68769