TY - JOUR
T1 - Mitochondrial respiration is decreased in visceral but not subcutaneous adipose tissue in obese individuals with fatty liver disease
AU - Pafili, Kalliopi
AU - Kahl, Sabine
AU - Mastrototaro, Lucia
AU - Strassburger, Klaus
AU - Pesta, Dominik
AU - Herder, Christian
AU - Pützer, Jennifer
AU - Dewidar, Bedair
AU - Hendlinger, Mona
AU - Granata, Cesare
AU - Saatmann, Nina
AU - Yavas, Aslihan
AU - Gancheva, Sofiya
AU - Heilmann, Geronimo
AU - Esposito, Irene
AU - Schlensak, Matthias
AU - Roden, Michael
N1 - Funding Information:
This study was supported in part by the DDZ, which is funded by the Ministry of Culture and Science of the State of North Rhine-Westphalia ( MKW NRW ) and the German Federal Ministry of Health ( BMG ), by grants of the German Federal Ministry of Education and Research ( BMBF ) to the German Center for Diabetes Research (DZD e. V., DZD Grant 2016). Parts of the study were also supported by grants from the European Funds for Regional Development (EFRE-0400191), EUREKA Eurostars-2 (E! 113230 DIA-PEP) and by grants from the German Research Foundation ( DFG , SFB 1116/2 , GRK 2576 ), the German Diabetes Association ( DDG ) and the Schmutzler-Stiftung. The funding sources had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Publisher Copyright:
© 2022 The Authors
PY - 2022/12
Y1 - 2022/12
N2 - 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 tissue-specific 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 (β = 0.985, p = 0.041) and with increased VAT protein expression of tumor necrosis factor A across all groups (β = −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. Clinical trial number: NCT01477957.
AB - 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 tissue-specific 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 (β = 0.985, p = 0.041) and with increased VAT protein expression of tumor necrosis factor A across all groups (β = −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. Clinical trial number: NCT01477957.
KW - Adiposity
KW - energy metabolism
KW - fat depots
KW - hepatic steatosis
KW - insulin-stimulated glucose disposal
UR - http://www.scopus.com/inward/record.url?scp=85138585387&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2022.08.010
DO - 10.1016/j.jhep.2022.08.010
M3 - Article
C2 - 35988689
AN - SCOPUS:85138585387
SN - 0168-8278
VL - 77
SP - 1504
EP - 1514
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 6
ER -
