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In Vivo Two-Photon Imaging Analysis of Dynamic Degradation of Hepatic Lipid Droplets in MS-275-Treated Mouse Liver

The accumulation of hepatic lipid droplets (LDs) is a hallmark of non-alcoholic fatty liver disease (NAFLD). Appropriate degradation of hepatic LDs and oxidation of complete free fatty acids (FFAs) are important for preventing the development of NAFLD. Histone deacetylase (HDAC) is involved in the i...

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Autores principales: Lee, Chang-Gun, Lee, Soo-Jin, Park, Seokho, Choi, Sung-E, Song, Min-Woo, Lee, Hyo Won, Kim, Hae Jin, Kang, Yup, Lee, Kwan Woo, Kim, Hwan Myung, Kwak, Jong-Young, Lee, In-Jeong, Jeon, Ja Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456374/
https://www.ncbi.nlm.nih.gov/pubmed/36077368
http://dx.doi.org/10.3390/ijms23179978
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author Lee, Chang-Gun
Lee, Soo-Jin
Park, Seokho
Choi, Sung-E
Song, Min-Woo
Lee, Hyo Won
Kim, Hae Jin
Kang, Yup
Lee, Kwan Woo
Kim, Hwan Myung
Kwak, Jong-Young
Lee, In-Jeong
Jeon, Ja Young
author_facet Lee, Chang-Gun
Lee, Soo-Jin
Park, Seokho
Choi, Sung-E
Song, Min-Woo
Lee, Hyo Won
Kim, Hae Jin
Kang, Yup
Lee, Kwan Woo
Kim, Hwan Myung
Kwak, Jong-Young
Lee, In-Jeong
Jeon, Ja Young
author_sort Lee, Chang-Gun
collection PubMed
description The accumulation of hepatic lipid droplets (LDs) is a hallmark of non-alcoholic fatty liver disease (NAFLD). Appropriate degradation of hepatic LDs and oxidation of complete free fatty acids (FFAs) are important for preventing the development of NAFLD. Histone deacetylase (HDAC) is involved in the impaired lipid metabolism seen in high-fat diet (HFD)-induced obese mice. Here, we evaluated the effect of MS-275, an inhibitor of HDAC1/3, on the degradation of hepatic LDs and FFA oxidation in HFD-induced NAFLD mice. To assess the dynamic degradation of hepatic LDs and FFA oxidation in fatty livers of MS-275-treated HFD C57BL/6J mice, an intravital two-photon imaging system was used and biochemical analysis was performed. The MS-275 improved hepatic metabolic alterations in HFD-induced fatty liver by increasing the dynamic degradation of hepatic LDs and the interaction between LDs and lysozyme in the fatty liver. Numerous peri-droplet mitochondria, lipolysis, and lipophagy were observed in the MS-275-treated mouse fatty liver. Biochemical analysis revealed that the lipolysis and autophagy pathways were activated in MS-275 treated mouse liver. In addition, MS-275 reduced the de novo lipogenesis, but increased the mitochondrial oxidation and the expression levels of oxidation-related genes, such as PPARa, MCAD, CPT1b, and FGF21. Taken together, these results suggest that MS-275 stimulates the degradation of hepatic LDs and mitochondrial free fatty acid oxidation, thus protecting against HFD-induced NAFLD.
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spelling pubmed-94563742022-09-09 In Vivo Two-Photon Imaging Analysis of Dynamic Degradation of Hepatic Lipid Droplets in MS-275-Treated Mouse Liver Lee, Chang-Gun Lee, Soo-Jin Park, Seokho Choi, Sung-E Song, Min-Woo Lee, Hyo Won Kim, Hae Jin Kang, Yup Lee, Kwan Woo Kim, Hwan Myung Kwak, Jong-Young Lee, In-Jeong Jeon, Ja Young Int J Mol Sci Article The accumulation of hepatic lipid droplets (LDs) is a hallmark of non-alcoholic fatty liver disease (NAFLD). Appropriate degradation of hepatic LDs and oxidation of complete free fatty acids (FFAs) are important for preventing the development of NAFLD. Histone deacetylase (HDAC) is involved in the impaired lipid metabolism seen in high-fat diet (HFD)-induced obese mice. Here, we evaluated the effect of MS-275, an inhibitor of HDAC1/3, on the degradation of hepatic LDs and FFA oxidation in HFD-induced NAFLD mice. To assess the dynamic degradation of hepatic LDs and FFA oxidation in fatty livers of MS-275-treated HFD C57BL/6J mice, an intravital two-photon imaging system was used and biochemical analysis was performed. The MS-275 improved hepatic metabolic alterations in HFD-induced fatty liver by increasing the dynamic degradation of hepatic LDs and the interaction between LDs and lysozyme in the fatty liver. Numerous peri-droplet mitochondria, lipolysis, and lipophagy were observed in the MS-275-treated mouse fatty liver. Biochemical analysis revealed that the lipolysis and autophagy pathways were activated in MS-275 treated mouse liver. In addition, MS-275 reduced the de novo lipogenesis, but increased the mitochondrial oxidation and the expression levels of oxidation-related genes, such as PPARa, MCAD, CPT1b, and FGF21. Taken together, these results suggest that MS-275 stimulates the degradation of hepatic LDs and mitochondrial free fatty acid oxidation, thus protecting against HFD-induced NAFLD. MDPI 2022-09-01 /pmc/articles/PMC9456374/ /pubmed/36077368 http://dx.doi.org/10.3390/ijms23179978 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Chang-Gun
Lee, Soo-Jin
Park, Seokho
Choi, Sung-E
Song, Min-Woo
Lee, Hyo Won
Kim, Hae Jin
Kang, Yup
Lee, Kwan Woo
Kim, Hwan Myung
Kwak, Jong-Young
Lee, In-Jeong
Jeon, Ja Young
In Vivo Two-Photon Imaging Analysis of Dynamic Degradation of Hepatic Lipid Droplets in MS-275-Treated Mouse Liver
title In Vivo Two-Photon Imaging Analysis of Dynamic Degradation of Hepatic Lipid Droplets in MS-275-Treated Mouse Liver
title_full In Vivo Two-Photon Imaging Analysis of Dynamic Degradation of Hepatic Lipid Droplets in MS-275-Treated Mouse Liver
title_fullStr In Vivo Two-Photon Imaging Analysis of Dynamic Degradation of Hepatic Lipid Droplets in MS-275-Treated Mouse Liver
title_full_unstemmed In Vivo Two-Photon Imaging Analysis of Dynamic Degradation of Hepatic Lipid Droplets in MS-275-Treated Mouse Liver
title_short In Vivo Two-Photon Imaging Analysis of Dynamic Degradation of Hepatic Lipid Droplets in MS-275-Treated Mouse Liver
title_sort in vivo two-photon imaging analysis of dynamic degradation of hepatic lipid droplets in ms-275-treated mouse liver
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456374/
https://www.ncbi.nlm.nih.gov/pubmed/36077368
http://dx.doi.org/10.3390/ijms23179978
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