Differential regulation of brain microvessel transcriptome and brain metabolome by western and heart-healthy dietary patterns in Ossabaw pigs
Abstract Diet is a potentially modifiable neurodegenerative disease risk factor. We studied the effects of a typical Western diet (WD; high in refined carbohydrates, cholesterol and saturated fat), relative to a heart-healthy diet (HHD; high in unrefined carbohydrates, polyunsaturated fat and fiber,...
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Nature Portfolio
2024-11-01
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| Online Access: | https://doi.org/10.1038/s41598-024-81321-1 |
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| author | Gloria Solano-Aguilar Gregory Matuszek Nirupa R. Matthan Alice H. Lichtenstein Xuedi Wang Sukla Lakshman Kathryn Barger Joseph F. Urban Aleksey Molokin Rachel E. Bennett Bradley T. Hyman Stefania Lamon-Fava |
| author_facet | Gloria Solano-Aguilar Gregory Matuszek Nirupa R. Matthan Alice H. Lichtenstein Xuedi Wang Sukla Lakshman Kathryn Barger Joseph F. Urban Aleksey Molokin Rachel E. Bennett Bradley T. Hyman Stefania Lamon-Fava |
| author_sort | Gloria Solano-Aguilar |
| collection | DOAJ |
| description | Abstract Diet is a potentially modifiable neurodegenerative disease risk factor. We studied the effects of a typical Western diet (WD; high in refined carbohydrates, cholesterol and saturated fat), relative to a heart-healthy diet (HHD; high in unrefined carbohydrates, polyunsaturated fat and fiber, and low in cholesterol) on brain microvessel transcriptomics and brain metabolomics of the temporal region in Ossabaw minipigs. Thirty-two pigs (16 male and 16 females) were fed a WD or HHD starting at the age of 4 months for a period of 6 months. The WD and HHD were isocaloric and had a similar macronutrient content but differed in macronutrient quality. Within each dietary group, half of the pigs also received atorvastatin. Relative to HHD-fed pigs, WD-fed pigs had 175 genes differentially expressed (fold change > 1.3, FDR < 0.05) by diet, 46 upregulated and 129 downregulated. Gene Set Enrichment Analysis identified 22 gene sets enriched in WD-fed pigs, comprising pathways related to inflammation, angiogenesis, and apoptosis, and 53 gene sets enriched in the HHD-fed pigs, including cell energetics, neurotransmission, and inflammation resolution pathways. Metabolite analysis showed enrichment in arginine, tyrosine, and lysine in WD-fed pigs, and ergothioneine and S-adenosyl methionine in HHD-fed pigs. Atorvastatin treatment did not affect gene expression. These results suggest a likely contribution of diet to brain pathologies characterized by neuroinflammation and neurodegeneration. |
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| id | doaj-art-7132af9e0f0c4276b4647f0cda0ab6c0 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-7132af9e0f0c4276b4647f0cda0ab6c02024-12-01T12:19:20ZengNature PortfolioScientific Reports2045-23222024-11-0114111310.1038/s41598-024-81321-1Differential regulation of brain microvessel transcriptome and brain metabolome by western and heart-healthy dietary patterns in Ossabaw pigsGloria Solano-Aguilar0Gregory Matuszek1Nirupa R. Matthan2Alice H. Lichtenstein3Xuedi Wang4Sukla Lakshman5Kathryn Barger6Joseph F. Urban7Aleksey Molokin8Rachel E. Bennett9Bradley T. Hyman10Stefania Lamon-Fava11Diet Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, USDA Northeast AreaBiostatistics Core Unit, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts UniversityCardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts UniversityCardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts UniversityGerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts UniversityDiet Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, USDA Northeast AreaBiostatistics Core Unit, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts UniversityDiet Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, USDA Northeast AreaDiet Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, USDA Northeast AreaDepartment of Neurology, Harvard Medical School and Massachusetts General Hospital Institute for Neurodegenerative DiseaseDepartment of Neurology, Harvard Medical School and Massachusetts General Hospital Institute for Neurodegenerative DiseaseCardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts UniversityAbstract Diet is a potentially modifiable neurodegenerative disease risk factor. We studied the effects of a typical Western diet (WD; high in refined carbohydrates, cholesterol and saturated fat), relative to a heart-healthy diet (HHD; high in unrefined carbohydrates, polyunsaturated fat and fiber, and low in cholesterol) on brain microvessel transcriptomics and brain metabolomics of the temporal region in Ossabaw minipigs. Thirty-two pigs (16 male and 16 females) were fed a WD or HHD starting at the age of 4 months for a period of 6 months. The WD and HHD were isocaloric and had a similar macronutrient content but differed in macronutrient quality. Within each dietary group, half of the pigs also received atorvastatin. Relative to HHD-fed pigs, WD-fed pigs had 175 genes differentially expressed (fold change > 1.3, FDR < 0.05) by diet, 46 upregulated and 129 downregulated. Gene Set Enrichment Analysis identified 22 gene sets enriched in WD-fed pigs, comprising pathways related to inflammation, angiogenesis, and apoptosis, and 53 gene sets enriched in the HHD-fed pigs, including cell energetics, neurotransmission, and inflammation resolution pathways. Metabolite analysis showed enrichment in arginine, tyrosine, and lysine in WD-fed pigs, and ergothioneine and S-adenosyl methionine in HHD-fed pigs. Atorvastatin treatment did not affect gene expression. These results suggest a likely contribution of diet to brain pathologies characterized by neuroinflammation and neurodegeneration.https://doi.org/10.1038/s41598-024-81321-1NeuroinflammationBrain microvesselsTranscriptomicsMetabolomics |
| spellingShingle | Gloria Solano-Aguilar Gregory Matuszek Nirupa R. Matthan Alice H. Lichtenstein Xuedi Wang Sukla Lakshman Kathryn Barger Joseph F. Urban Aleksey Molokin Rachel E. Bennett Bradley T. Hyman Stefania Lamon-Fava Differential regulation of brain microvessel transcriptome and brain metabolome by western and heart-healthy dietary patterns in Ossabaw pigs Scientific Reports Neuroinflammation Brain microvessels Transcriptomics Metabolomics |
| title | Differential regulation of brain microvessel transcriptome and brain metabolome by western and heart-healthy dietary patterns in Ossabaw pigs |
| title_full | Differential regulation of brain microvessel transcriptome and brain metabolome by western and heart-healthy dietary patterns in Ossabaw pigs |
| title_fullStr | Differential regulation of brain microvessel transcriptome and brain metabolome by western and heart-healthy dietary patterns in Ossabaw pigs |
| title_full_unstemmed | Differential regulation of brain microvessel transcriptome and brain metabolome by western and heart-healthy dietary patterns in Ossabaw pigs |
| title_short | Differential regulation of brain microvessel transcriptome and brain metabolome by western and heart-healthy dietary patterns in Ossabaw pigs |
| title_sort | differential regulation of brain microvessel transcriptome and brain metabolome by western and heart healthy dietary patterns in ossabaw pigs |
| topic | Neuroinflammation Brain microvessels Transcriptomics Metabolomics |
| url | https://doi.org/10.1038/s41598-024-81321-1 |
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