Western diet promotes the progression of metabolic dysfunction‐associated steatotic liver disease in association with ferroptosis in male mice
Abstract Non‐alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction‐associated steatotic liver disease (MASLD), is a silent killer that often progresses to metabolic dysfunction‐associated steatohepatitis (MASH). To date, there are no pharmacological treatments for MASLD. Wh...
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| Language: | English |
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Wiley
2024-11-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.70139 |
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| author | Nicole Maddie Nefia Chacko David Matatov Maria Alicia Carrillo‐Sepulveda |
| author_facet | Nicole Maddie Nefia Chacko David Matatov Maria Alicia Carrillo‐Sepulveda |
| author_sort | Nicole Maddie |
| collection | DOAJ |
| description | Abstract Non‐alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction‐associated steatotic liver disease (MASLD), is a silent killer that often progresses to metabolic dysfunction‐associated steatohepatitis (MASH). To date, there are no pharmacological treatments for MASLD. While obesity is a major cause of the development and progression of MASLD, the underlying mechanisms remain unclear. We hypothesize that ferroptosis, a recently discovered nonapoptotic iron‐dependent form of cell death, is activated during the progression of MASLD and may be a potential target for treating MASLD. Using a murine model of Western diet‐induced obesity, C57BL/6J male mice were exposed to a long‐term (36 weeks) Western diet. Controls were maintained with a standard chow diet. Western diet‐induced obesity was confirmed by increased body mass index (BMI). Histopathological analysis demonstrated the progression of MASLD to MASH in the obese group, which was accompanied by significant hepatic iron deposition, oxidative damage, and lipid peroxidation. Hepatic ferroptosis was further confirmed by decreased protein expression of glutathione peroxidase 4 (GPX4) and increased acyl‐CoA synthetase long‐chain family member 4 (ACSL4), markers of ferroptosis. These findings suggest that ferroptosis is a potential mechanism involved in the pathogenesis of MASLD in male mice. |
| format | Article |
| id | doaj-art-2f1eb223a2194855b5c7656bc71c822c |
| institution | Kabale University |
| issn | 2051-817X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj-art-2f1eb223a2194855b5c7656bc71c822c2025-01-10T11:14:29ZengWileyPhysiological Reports2051-817X2024-11-011223n/an/a10.14814/phy2.70139Western diet promotes the progression of metabolic dysfunction‐associated steatotic liver disease in association with ferroptosis in male miceNicole Maddie0Nefia Chacko1David Matatov2Maria Alicia Carrillo‐Sepulveda3Department of Biomedical Sciences, College of Osteopathic Medicine New York Institute of Technology Old Westbury New York USADepartment of Biomedical Sciences, College of Osteopathic Medicine New York Institute of Technology Old Westbury New York USADepartment of Biomedical Sciences, College of Osteopathic Medicine New York Institute of Technology Old Westbury New York USADepartment of Biomedical Sciences, College of Osteopathic Medicine New York Institute of Technology Old Westbury New York USAAbstract Non‐alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction‐associated steatotic liver disease (MASLD), is a silent killer that often progresses to metabolic dysfunction‐associated steatohepatitis (MASH). To date, there are no pharmacological treatments for MASLD. While obesity is a major cause of the development and progression of MASLD, the underlying mechanisms remain unclear. We hypothesize that ferroptosis, a recently discovered nonapoptotic iron‐dependent form of cell death, is activated during the progression of MASLD and may be a potential target for treating MASLD. Using a murine model of Western diet‐induced obesity, C57BL/6J male mice were exposed to a long‐term (36 weeks) Western diet. Controls were maintained with a standard chow diet. Western diet‐induced obesity was confirmed by increased body mass index (BMI). Histopathological analysis demonstrated the progression of MASLD to MASH in the obese group, which was accompanied by significant hepatic iron deposition, oxidative damage, and lipid peroxidation. Hepatic ferroptosis was further confirmed by decreased protein expression of glutathione peroxidase 4 (GPX4) and increased acyl‐CoA synthetase long‐chain family member 4 (ACSL4), markers of ferroptosis. These findings suggest that ferroptosis is a potential mechanism involved in the pathogenesis of MASLD in male mice.https://doi.org/10.14814/phy2.70139ferroptosisGPX4MASHMASLDobesityWestern diet |
| spellingShingle | Nicole Maddie Nefia Chacko David Matatov Maria Alicia Carrillo‐Sepulveda Western diet promotes the progression of metabolic dysfunction‐associated steatotic liver disease in association with ferroptosis in male mice Physiological Reports ferroptosis GPX4 MASH MASLD obesity Western diet |
| title | Western diet promotes the progression of metabolic dysfunction‐associated steatotic liver disease in association with ferroptosis in male mice |
| title_full | Western diet promotes the progression of metabolic dysfunction‐associated steatotic liver disease in association with ferroptosis in male mice |
| title_fullStr | Western diet promotes the progression of metabolic dysfunction‐associated steatotic liver disease in association with ferroptosis in male mice |
| title_full_unstemmed | Western diet promotes the progression of metabolic dysfunction‐associated steatotic liver disease in association with ferroptosis in male mice |
| title_short | Western diet promotes the progression of metabolic dysfunction‐associated steatotic liver disease in association with ferroptosis in male mice |
| title_sort | western diet promotes the progression of metabolic dysfunction associated steatotic liver disease in association with ferroptosis in male mice |
| topic | ferroptosis GPX4 MASH MASLD obesity Western diet |
| url | https://doi.org/10.14814/phy2.70139 |
| work_keys_str_mv | AT nicolemaddie westerndietpromotestheprogressionofmetabolicdysfunctionassociatedsteatoticliverdiseaseinassociationwithferroptosisinmalemice AT nefiachacko westerndietpromotestheprogressionofmetabolicdysfunctionassociatedsteatoticliverdiseaseinassociationwithferroptosisinmalemice AT davidmatatov westerndietpromotestheprogressionofmetabolicdysfunctionassociatedsteatoticliverdiseaseinassociationwithferroptosisinmalemice AT mariaaliciacarrillosepulveda westerndietpromotestheprogressionofmetabolicdysfunctionassociatedsteatoticliverdiseaseinassociationwithferroptosisinmalemice |