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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MDPI AG
2022-09-01
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| author | Chang-Gun Lee Soo-Jin Lee Seokho Park Sung-E Choi Min-Woo Song Hyo Won Lee Hae Jin Kim Yup Kang Kwan Woo Lee Hwan Myung Kim Jong-Young Kwak In-Jeong Lee Ja Young Jeon |
| author_facet | Chang-Gun Lee Soo-Jin Lee Seokho Park Sung-E Choi Min-Woo Song Hyo Won Lee Hae Jin Kim Yup Kang Kwan Woo Lee Hwan Myung Kim Jong-Young Kwak In-Jeong Lee Ja Young Jeon |
| author_sort | Chang-Gun Lee |
| collection | DOAJ |
| 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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| last_indexed | 2024-03-10T01:43:34Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b34e3d41f59a4508be2c3fbe89e5400d2023-11-23T13:20:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-012317997810.3390/ijms23179978In Vivo Two-Photon Imaging Analysis of Dynamic Degradation of Hepatic Lipid Droplets in MS-275-Treated Mouse LiverChang-Gun Lee0Soo-Jin Lee1Seokho Park2Sung-E Choi3Min-Woo Song4Hyo Won Lee5Hae Jin Kim6Yup Kang7Kwan Woo Lee8Hwan Myung Kim9Jong-Young Kwak10In-Jeong Lee11Ja Young Jeon12Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, KoreaThree-Dimensional Immune System Imaging Core Facility, Ajou University, Suwon 16499, Gyeonggi-do, KoreaDepartment of Physiology, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, KoreaDepartment of Physiology, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, KoreaDepartment of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, KoreaDepartment of Energy Systems Research, Ajou University, Suwon 16499, Gyeonggi-do, KoreaDepartment of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, KoreaDepartment of Physiology, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, KoreaDepartment of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, KoreaDepartment of Energy Systems Research, Ajou University, Suwon 16499, Gyeonggi-do, KoreaThree-Dimensional Immune System Imaging Core Facility, Ajou University, Suwon 16499, Gyeonggi-do, KoreaThree-Dimensional Immune System Imaging Core Facility, Ajou University, Suwon 16499, Gyeonggi-do, KoreaDepartment of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, KoreaThe 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.https://www.mdpi.com/1422-0067/23/17/9978MS-275NAFLDfatty liverintravital imagingFGF21mitochondrial oxidation |
| spellingShingle | Chang-Gun Lee Soo-Jin Lee Seokho Park Sung-E Choi Min-Woo Song Hyo Won Lee Hae Jin Kim Yup Kang Kwan Woo Lee Hwan Myung Kim Jong-Young Kwak In-Jeong Lee Ja Young Jeon In Vivo Two-Photon Imaging Analysis of Dynamic Degradation of Hepatic Lipid Droplets in MS-275-Treated Mouse Liver International Journal of Molecular Sciences MS-275 NAFLD fatty liver intravital imaging FGF21 mitochondrial oxidation |
| 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 | MS-275 NAFLD fatty liver intravital imaging FGF21 mitochondrial oxidation |
| url | https://www.mdpi.com/1422-0067/23/17/9978 |
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