Article ; Online: Alterations in Cytoskeleton and Mitochondria in the Development and Reversal of Steatosis in Human Hepatocytes.
Cellular and molecular gastroenterology and hepatology
2023 Volume 16, Issue 2, Page(s) 243–261
Abstract: Background & aims: Alterations in mitochondrial morphology and function and increased oxidative stresses in hepatocytes are well established in nonalcoholic fatty liver disease (NAFLD). Patients can undergo lifestyle changes, especially in earlier NAFLD ...
| Abstract | Background & aims: Alterations in mitochondrial morphology and function and increased oxidative stresses in hepatocytes are well established in nonalcoholic fatty liver disease (NAFLD). Patients can undergo lifestyle changes, especially in earlier NAFLD stages, to reverse disease-induced phenotypes on a gross level. Yet, little is known about whether mitochondrial function and injuries recover upon reversal. Thus, we elucidated this question and interplays between the cytoskeletal network and mitochondria in the development and reversal of steatosis. Methods: We cultured primary human hepatocytes stably for 2 weeks and used free fatty acid supplementation to induce steatosis over 7 days and reversed steatosis by free fatty acid withdrawal over the next 7 days. We assessed cytoskeletal and mitochondrial morphologies using immunocytochemistry and confocal microscopy. We evaluated mitochondrial respiration and function via the Seahorse analyzer, in which we fully optimized reagent dosing specifically for human hepatocytes. Results: During early steatosis, intracellular lipid droplets displaced microtubules altering mitochondrial distribution, and disrupted the F-actin network, leading to loss of bile canaliculi in steatotic hepatocytes. Basal mitochondrial respiration, maximum respiratory capacity, and resistance to H Conclusions: Despite the restoration of cytoskeletons morphologically upon reversal of steatosis, the mitochondria in hepatocytes were impaired owing to early adaptative respiratory increase. Hepatocytes thus were highly predisposed to H |
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| MeSH term(s) | Humans ; Non-alcoholic Fatty Liver Disease/metabolism ; Fatty Acids, Nonesterified/metabolism ; Actins/metabolism ; Hydrogen Peroxide/metabolism ; Hepatocytes/metabolism ; Mitochondria/metabolism ; Cytoskeleton/metabolism ; Microtubules/metabolism |
| Chemical Substances | Fatty Acids, Nonesterified ; Actins ; Hydrogen Peroxide (BBX060AN9V) |
| Language | English |
| Publishing date | 2023-04-20 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2819778-1 |
| ISSN | 2352-345X ; 2352-345X |
| ISSN (online) | 2352-345X |
| ISSN | 2352-345X |
| DOI | 10.1016/j.jcmgh.2023.04.003 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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