P-2 DE NOVO LIPOGENESIS MARKERS ARE INVOLVED IN METABOLIC ASSOCIATED FATTY LIVER DISEASE PROGRESSION IN BTBR OB/OB MICE
Introduction and Objectives: The new recommendations suggesting changing the current nomenclature from Non-Alcoholic Fatty Liver Disease (NAFLD) to Metabolic associated fatty liver disease (MAFLD) are primarily aimed at improving the understanding of the disease. MAFLD is a hepatic manifestation of...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Annals of Hepatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268123000108 |
| _version_ | 1797862206491066368 |
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| author | Lucas Opazo-Rios Manuel Soto-Catalan Iolanda Lázaro Aleix Sala-Vila Cristian Pérez-Gallardo Fabian Segovia-Miranda Juan Antonio Moreno Jesús Egido Sebastián Mas-Fontao |
| author_facet | Lucas Opazo-Rios Manuel Soto-Catalan Iolanda Lázaro Aleix Sala-Vila Cristian Pérez-Gallardo Fabian Segovia-Miranda Juan Antonio Moreno Jesús Egido Sebastián Mas-Fontao |
| author_sort | Lucas Opazo-Rios |
| collection | DOAJ |
| description | Introduction and Objectives: The new recommendations suggesting changing the current nomenclature from Non-Alcoholic Fatty Liver Disease (NAFLD) to Metabolic associated fatty liver disease (MAFLD) are primarily aimed at improving the understanding of the disease. MAFLD is a hepatic manifestation of metabolic syndrome and is usually associated with obesity and type 2 diabetes, excluding other causes not associated with positive energy balance. This study aimed to characterize the pathophysiological mechanism involved in MAFLD development in susceptible-strain Black Tan and brachyuric (BTBR) insulin-resistant mice in combination with leptin deficiency (ob/ob). Materials and Methods: We studied liver morphology and biochemistry on our diabetic and obese mice model (BTBR ob/ob) as well as a diabetic non-obese control (BTBR + streptozotocin) and non-diabetic control mice (BTBR wild type) from 4-22 weeks. The lipid composition was assessed and lipid-related pathways were studied at transcriptional and protein levels. Results: Microvesicular steatosis was evident in BTBR ob/ob from week 6, progressing to macrovesicular in the following weeks. At the 12th week, inflammatory clusters, activation of STAT3 and Nrf2 signaling pathways, and hepatocellular ballooning. At 22 weeks, the histopathological features previously observed were maintained and no signs of fibrosis were detected. Liver gene-expression analysis demonstrated modifications in fatty acid transporters associated with uptake (Cd36, Cd204, Fatp4)/efflux (Abca1, Abcg1), de novo fatty acid synthesis enzymes (ACC, FASN, SCD-1) and transcription factors related to lipogenic pathways (Pparα/γ, Srebp-1, Chrebp-1). Additionally, the lipidomic analysis showed profiles associated with de novo lipogenesis (DNL), showing a significant increase in palmitic acid (C16:0), palmitoleic acid (C16:1n7) and oleic acid (C18:1n9). Conclusions: BTBR ob/ob mice develop MAFLD profiles that resemble pathological features observed in humans, with overactivation of inflammatory response, oxidative stress and DNL signaling pathways. Therefore, BTBR ob/ob mouse is an excellent model for the study of the steatosis to steatohepatitis transition. |
| first_indexed | 2024-04-09T22:16:34Z |
| format | Article |
| id | doaj.art-c872cd79e05b4246a16d87507c1b5579 |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-04-09T22:16:34Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-c872cd79e05b4246a16d87507c1b55792023-03-23T04:33:49ZengElsevierAnnals of Hepatology1665-26812023-03-0128100906P-2 DE NOVO LIPOGENESIS MARKERS ARE INVOLVED IN METABOLIC ASSOCIATED FATTY LIVER DISEASE PROGRESSION IN BTBR OB/OB MICELucas Opazo-Rios0Manuel Soto-Catalan1Iolanda Lázaro2Aleix Sala-Vila3Cristian Pérez-Gallardo4Fabian Segovia-Miranda5Juan Antonio Moreno6Jesús Egido7Sebastián Mas-Fontao8Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28040 Madrid, Spain; Facultad de Ciencias de la Salud, Universidad de Las Américas, 4301099, Concepción-Talcahuano, ChileRenal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28040 Madrid, SpainHospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, SpainHospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, SpainDepartment of Cell Biology, Faculty of Biological Sciences, Universidad de Concepción, Concepción, ChileDepartment of Cell Biology, Faculty of Biological Sciences, Universidad de Concepción, Concepción, ChileDepartment of Cell Biology, Physiology and Immunology, University of Cordoba; Maimonides Biomedical Research Institute of Cordoba (IMIBIC); UGC Nephrology, Hospital Universitario Reina Sofía, 14004 Cordoba, SpainRenal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28040 Madrid, SpainRenal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28040 Madrid, SpainIntroduction and Objectives: The new recommendations suggesting changing the current nomenclature from Non-Alcoholic Fatty Liver Disease (NAFLD) to Metabolic associated fatty liver disease (MAFLD) are primarily aimed at improving the understanding of the disease. MAFLD is a hepatic manifestation of metabolic syndrome and is usually associated with obesity and type 2 diabetes, excluding other causes not associated with positive energy balance. This study aimed to characterize the pathophysiological mechanism involved in MAFLD development in susceptible-strain Black Tan and brachyuric (BTBR) insulin-resistant mice in combination with leptin deficiency (ob/ob). Materials and Methods: We studied liver morphology and biochemistry on our diabetic and obese mice model (BTBR ob/ob) as well as a diabetic non-obese control (BTBR + streptozotocin) and non-diabetic control mice (BTBR wild type) from 4-22 weeks. The lipid composition was assessed and lipid-related pathways were studied at transcriptional and protein levels. Results: Microvesicular steatosis was evident in BTBR ob/ob from week 6, progressing to macrovesicular in the following weeks. At the 12th week, inflammatory clusters, activation of STAT3 and Nrf2 signaling pathways, and hepatocellular ballooning. At 22 weeks, the histopathological features previously observed were maintained and no signs of fibrosis were detected. Liver gene-expression analysis demonstrated modifications in fatty acid transporters associated with uptake (Cd36, Cd204, Fatp4)/efflux (Abca1, Abcg1), de novo fatty acid synthesis enzymes (ACC, FASN, SCD-1) and transcription factors related to lipogenic pathways (Pparα/γ, Srebp-1, Chrebp-1). Additionally, the lipidomic analysis showed profiles associated with de novo lipogenesis (DNL), showing a significant increase in palmitic acid (C16:0), palmitoleic acid (C16:1n7) and oleic acid (C18:1n9). Conclusions: BTBR ob/ob mice develop MAFLD profiles that resemble pathological features observed in humans, with overactivation of inflammatory response, oxidative stress and DNL signaling pathways. Therefore, BTBR ob/ob mouse is an excellent model for the study of the steatosis to steatohepatitis transition.http://www.sciencedirect.com/science/article/pii/S1665268123000108 |
| spellingShingle | Lucas Opazo-Rios Manuel Soto-Catalan Iolanda Lázaro Aleix Sala-Vila Cristian Pérez-Gallardo Fabian Segovia-Miranda Juan Antonio Moreno Jesús Egido Sebastián Mas-Fontao P-2 DE NOVO LIPOGENESIS MARKERS ARE INVOLVED IN METABOLIC ASSOCIATED FATTY LIVER DISEASE PROGRESSION IN BTBR OB/OB MICE Annals of Hepatology |
| title | P-2 DE NOVO LIPOGENESIS MARKERS ARE INVOLVED IN METABOLIC ASSOCIATED FATTY LIVER DISEASE PROGRESSION IN BTBR OB/OB MICE |
| title_full | P-2 DE NOVO LIPOGENESIS MARKERS ARE INVOLVED IN METABOLIC ASSOCIATED FATTY LIVER DISEASE PROGRESSION IN BTBR OB/OB MICE |
| title_fullStr | P-2 DE NOVO LIPOGENESIS MARKERS ARE INVOLVED IN METABOLIC ASSOCIATED FATTY LIVER DISEASE PROGRESSION IN BTBR OB/OB MICE |
| title_full_unstemmed | P-2 DE NOVO LIPOGENESIS MARKERS ARE INVOLVED IN METABOLIC ASSOCIATED FATTY LIVER DISEASE PROGRESSION IN BTBR OB/OB MICE |
| title_short | P-2 DE NOVO LIPOGENESIS MARKERS ARE INVOLVED IN METABOLIC ASSOCIATED FATTY LIVER DISEASE PROGRESSION IN BTBR OB/OB MICE |
| title_sort | p 2 de novo lipogenesis markers are involved in metabolic associated fatty liver disease progression in btbr ob ob mice |
| url | http://www.sciencedirect.com/science/article/pii/S1665268123000108 |
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