Compromised hepatic mitochondrial fatty acid oxidation and reduced markers of mitochondrial turnover in human NAFLD.

Autor: Moore MP; Research Service, Harry S. Truman Memorial Veterans Medical Center, Columbia, Missouri, USA.; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA., Cunningham RP; Research Service, Harry S. Truman Memorial Veterans Medical Center, Columbia, Missouri, USA.; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA., Meers GM; Research Service, Harry S. Truman Memorial Veterans Medical Center, Columbia, Missouri, USA.; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA., Johnson SA; Research Service, Harry S. Truman Memorial Veterans Medical Center, Columbia, Missouri, USA.; Department of Medicine-Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri, USA., Wheeler AA; Department of Surgery, University of Missouri, Columbia, Missouri, USA., Ganga RR; Department of Surgery, University of Missouri, Columbia, Missouri, USA., Spencer NM; Department of Surgery, University of Missouri, Columbia, Missouri, USA., Pitt JB; Department of Surgery, University of Missouri, Columbia, Missouri, USA., Diaz-Arias A; Boyce and Bynum Pathology Professional Services, Columbia, Missouri, USA., Swi AIA; Department of Medicine-Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri, USA., Hammoud GM; Department of Medicine-Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri, USA., Ibdah JA; Research Service, Harry S. Truman Memorial Veterans Medical Center, Columbia, Missouri, USA.; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA.; Department of Medicine-Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri, USA., Parks EJ; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA.; Department of Medicine-Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri, USA., Rector RS; Research Service, Harry S. Truman Memorial Veterans Medical Center, Columbia, Missouri, USA.; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA.; Department of Medicine-Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri, USA.
Jazyk: angličtina
Zdroj: Hepatology (Baltimore, Md.) [Hepatology] 2022 Nov; Vol. 76 (5), pp. 1452-1465. Date of Electronic Publication: 2022 Apr 14.
DOI: 10.1002/hep.32324
Abstrakt: Background and Aims: NAFLD and its more-advanced form, steatohepatitis (NASH), is associated with obesity and is an independent risk factor for cardiovascular, liver-related, and all-cause mortality. Available human data examining hepatic mitochondrial fatty acid oxidation (FAO) and hepatic mitochondrial turnover in NAFLD and NASH are scant.
Approach and Results: To investigate this relationship, liver biopsies were obtained from patients with obesity undergoing bariatric surgery and data clustered into four groups based on hepatic histopathological classification: Control (CTRL; no disease); NAFL (steatosis only); Borderline-NASH (steatosis with lobular inflammation or hepatocellular ballooning); and Definite-NASH (D-NASH; steatosis, lobular inflammation, and hepatocellular ballooning). Hepatic mitochondrial complete FAO to CO 2 and the rate-limiting enzyme in β-oxidation (β-hydroxyacyl-CoA dehydrogenase activity) were reduced by ~40%-50% with D-NASH compared with CTRL. This corresponded with increased hepatic mitochondrial reactive oxygen species production, as well as dramatic reductions in markers of mitochondrial biogenesis, autophagy, mitophagy, fission, and fusion in NAFL and NASH.
Conclusions: These findings suggest that compromised hepatic FAO and mitochondrial turnover are intimately linked to increasing NAFLD severity in patients with obesity.
(© 2022 American Association for the Study of Liver Diseases.)
Databáze: MEDLINE
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