High-fat diet reveals the impact of Sar1b defects on lipid and lipoprotein profile and cholesterol metabolism
Biallelic pathogenic variants of the Sar1b gene cause chylomicron retention disease (CRD) whose central phenotype is the inability to secrete chylomicrons. Patients with CRD experience numerous clinical symptoms such as gastrointestinal, hepatic, neuromuscular, ophthalmic, and cardiological abnormal...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227523000962 |
| _version_ | 1797676724258865152 |
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| author | Nickolas Auclair Alain T. Sané Léna Ahmarani Nour-El-Houda Ould-Chikh Nathalie Patey Jean-François Beaulieu Edgard Delvin Schohraya Spahis Emile Levy |
| author_facet | Nickolas Auclair Alain T. Sané Léna Ahmarani Nour-El-Houda Ould-Chikh Nathalie Patey Jean-François Beaulieu Edgard Delvin Schohraya Spahis Emile Levy |
| author_sort | Nickolas Auclair |
| collection | DOAJ |
| description | Biallelic pathogenic variants of the Sar1b gene cause chylomicron retention disease (CRD) whose central phenotype is the inability to secrete chylomicrons. Patients with CRD experience numerous clinical symptoms such as gastrointestinal, hepatic, neuromuscular, ophthalmic, and cardiological abnormalities. Recently, the production of mice expressing either a targeted deletion or mutation of Sar1b recapitulated biochemical and gastrointestinal defects associated with CRD. The present study was conducted to better understand little-known aspects of Sar1b mutations, including mouse embryonic development, lipid profile, and lipoprotein composition in response to high-fat diet, gut and liver cholesterol metabolism, sex-specific effects, and genotype-phenotype differences. Sar1b deletion and mutation produce a lethal phenotype in homozygous mice, which display intestinal lipid accumulation without any gross morphological abnormalities. On high-fat diet, mutant mice exhibit more marked abnormalities in body composition, adipose tissue and liver weight, plasma cholesterol, non-HDL cholesterol and polyunsaturated fatty acids than those on the regular Chow diet. Divergences were also noted in lipoprotein lipid composition, lipid ratios (serving as indices of particle size) and lipoprotein-apolipoprotein distribution. Sar1b defects significantly reduce gut cholesterol accumulation while altering key players in cholesterol metabolism. Noteworthy, variations were observed between males and females, and between Sar1b deletion and mutation phenotypes. Overall, mutant animal findings reveal the importance of Sar1b in several biochemical, metabolic and developmental processes. |
| first_indexed | 2024-03-11T22:33:30Z |
| format | Article |
| id | doaj.art-fac6eb6ad59e469280811c93cc3f46d2 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-03-11T22:33:30Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-fac6eb6ad59e469280811c93cc3f46d22023-09-23T05:09:47ZengElsevierJournal of Lipid Research0022-22752023-09-01649100423High-fat diet reveals the impact of Sar1b defects on lipid and lipoprotein profile and cholesterol metabolismNickolas Auclair0Alain T. Sané1Léna Ahmarani2Nour-El-Houda Ould-Chikh3Nathalie Patey4Jean-François Beaulieu5Edgard Delvin6Schohraya Spahis7Emile Levy8Research Center, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada; Department of Pharmacology & Physiology, Université de Montréal, Montreal, Quebec, CanadaResearch Center, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, CanadaResearch Center, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, CanadaResearch Center, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, CanadaResearch Center, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, CanadaLaboratory of Intestinal Physiopathology, Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, CanadaResearch Center, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, CanadaResearch Center, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada; Department of Nutrition, Université de Montréal, Montreal, Quebec, CanadaResearch Center, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada; Department of Pharmacology & Physiology, Université de Montréal, Montreal, Quebec, Canada; Department of Nutrition, Université de Montréal, Montreal, Quebec, Canada; For correspondence: Emile LevyBiallelic pathogenic variants of the Sar1b gene cause chylomicron retention disease (CRD) whose central phenotype is the inability to secrete chylomicrons. Patients with CRD experience numerous clinical symptoms such as gastrointestinal, hepatic, neuromuscular, ophthalmic, and cardiological abnormalities. Recently, the production of mice expressing either a targeted deletion or mutation of Sar1b recapitulated biochemical and gastrointestinal defects associated with CRD. The present study was conducted to better understand little-known aspects of Sar1b mutations, including mouse embryonic development, lipid profile, and lipoprotein composition in response to high-fat diet, gut and liver cholesterol metabolism, sex-specific effects, and genotype-phenotype differences. Sar1b deletion and mutation produce a lethal phenotype in homozygous mice, which display intestinal lipid accumulation without any gross morphological abnormalities. On high-fat diet, mutant mice exhibit more marked abnormalities in body composition, adipose tissue and liver weight, plasma cholesterol, non-HDL cholesterol and polyunsaturated fatty acids than those on the regular Chow diet. Divergences were also noted in lipoprotein lipid composition, lipid ratios (serving as indices of particle size) and lipoprotein-apolipoprotein distribution. Sar1b defects significantly reduce gut cholesterol accumulation while altering key players in cholesterol metabolism. Noteworthy, variations were observed between males and females, and between Sar1b deletion and mutation phenotypes. Overall, mutant animal findings reveal the importance of Sar1b in several biochemical, metabolic and developmental processes.http://www.sciencedirect.com/science/article/pii/S0022227523000962Sar1b genechylomicronintestinal fat malabsorptionlipoprotein compositionembryonic lethalityhigh-fat diet |
| spellingShingle | Nickolas Auclair Alain T. Sané Léna Ahmarani Nour-El-Houda Ould-Chikh Nathalie Patey Jean-François Beaulieu Edgard Delvin Schohraya Spahis Emile Levy High-fat diet reveals the impact of Sar1b defects on lipid and lipoprotein profile and cholesterol metabolism Journal of Lipid Research Sar1b gene chylomicron intestinal fat malabsorption lipoprotein composition embryonic lethality high-fat diet |
| title | High-fat diet reveals the impact of Sar1b defects on lipid and lipoprotein profile and cholesterol metabolism |
| title_full | High-fat diet reveals the impact of Sar1b defects on lipid and lipoprotein profile and cholesterol metabolism |
| title_fullStr | High-fat diet reveals the impact of Sar1b defects on lipid and lipoprotein profile and cholesterol metabolism |
| title_full_unstemmed | High-fat diet reveals the impact of Sar1b defects on lipid and lipoprotein profile and cholesterol metabolism |
| title_short | High-fat diet reveals the impact of Sar1b defects on lipid and lipoprotein profile and cholesterol metabolism |
| title_sort | high fat diet reveals the impact of sar1b defects on lipid and lipoprotein profile and cholesterol metabolism |
| topic | Sar1b gene chylomicron intestinal fat malabsorption lipoprotein composition embryonic lethality high-fat diet |
| url | http://www.sciencedirect.com/science/article/pii/S0022227523000962 |
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