Maternal obesity increases hypothalamic miR-505-5p expression in mouse offspring leading to altered fatty acid sensing and increased intake of high-fat food.
In utero exposure to maternal obesity programs increased obesity risk. Animal models show that programmed offspring obesity is preceded by hyperphagia, but the mechanisms that mediate these changes are unknown. Using a mouse model of maternal obesity, we observed increased intake of a high-fat diet...
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Public Library of Science (PLoS)
2024-06-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002641&type=printable |
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| author | Laura Dearden Isadora C Furigo Lucas C Pantaleão L W P Wong Denise S Fernandez-Twinn Juliana de Almeida-Faria Katherine A Kentistou Maria V Carreira Guillaume Bidault Antonio Vidal-Puig Ken K Ong John R B Perry Jose Donato Susan E Ozanne |
| author_facet | Laura Dearden Isadora C Furigo Lucas C Pantaleão L W P Wong Denise S Fernandez-Twinn Juliana de Almeida-Faria Katherine A Kentistou Maria V Carreira Guillaume Bidault Antonio Vidal-Puig Ken K Ong John R B Perry Jose Donato Susan E Ozanne |
| author_sort | Laura Dearden |
| collection | DOAJ |
| description | In utero exposure to maternal obesity programs increased obesity risk. Animal models show that programmed offspring obesity is preceded by hyperphagia, but the mechanisms that mediate these changes are unknown. Using a mouse model of maternal obesity, we observed increased intake of a high-fat diet (HFD) in offspring of obese mothers that precedes the development of obesity. Through small RNA sequencing, we identified programmed overexpression of hypothalamic miR-505-5p that is established in the fetus, lasts to adulthood and is maintained in hypothalamic neural progenitor cells cultured in vitro. Metabolic hormones and long-chain fatty acids associated with obesity increase miR-505-5p expression in hypothalamic neurons in vitro. We demonstrate that targets of miR-505-5p are enriched in fatty acid metabolism pathways and overexpression of miR-505-5p decreased neuronal fatty acid metabolism in vitro. miR-505-5p targets are associated with increased BMI in human genetic studies. Intra-cerebroventricular injection of miR-505-5p in wild-type mice increased HFD intake, mimicking the phenotype observed in offspring exposed to maternal obesity. Conversely, maternal exercise intervention in an obese mouse pregnancy rescued the programmed increase of hypothalamic miR-505-5p in offspring of obese dams and reduced HFD intake to control offspring levels. This study identifies a novel mechanism by which maternal obesity programs obesity in offspring via increased intake of high-fat foods. |
| format | Article |
| id | doaj-art-ab9fe1aaf89243808133bb36842e17d9 |
| institution | Kabale University |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-ab9fe1aaf89243808133bb36842e17d92025-02-05T05:30:18ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852024-06-01226e300264110.1371/journal.pbio.3002641Maternal obesity increases hypothalamic miR-505-5p expression in mouse offspring leading to altered fatty acid sensing and increased intake of high-fat food.Laura DeardenIsadora C FurigoLucas C PantaleãoL W P WongDenise S Fernandez-TwinnJuliana de Almeida-FariaKatherine A KentistouMaria V CarreiraGuillaume BidaultAntonio Vidal-PuigKen K OngJohn R B PerryJose DonatoSusan E OzanneIn utero exposure to maternal obesity programs increased obesity risk. Animal models show that programmed offspring obesity is preceded by hyperphagia, but the mechanisms that mediate these changes are unknown. Using a mouse model of maternal obesity, we observed increased intake of a high-fat diet (HFD) in offspring of obese mothers that precedes the development of obesity. Through small RNA sequencing, we identified programmed overexpression of hypothalamic miR-505-5p that is established in the fetus, lasts to adulthood and is maintained in hypothalamic neural progenitor cells cultured in vitro. Metabolic hormones and long-chain fatty acids associated with obesity increase miR-505-5p expression in hypothalamic neurons in vitro. We demonstrate that targets of miR-505-5p are enriched in fatty acid metabolism pathways and overexpression of miR-505-5p decreased neuronal fatty acid metabolism in vitro. miR-505-5p targets are associated with increased BMI in human genetic studies. Intra-cerebroventricular injection of miR-505-5p in wild-type mice increased HFD intake, mimicking the phenotype observed in offspring exposed to maternal obesity. Conversely, maternal exercise intervention in an obese mouse pregnancy rescued the programmed increase of hypothalamic miR-505-5p in offspring of obese dams and reduced HFD intake to control offspring levels. This study identifies a novel mechanism by which maternal obesity programs obesity in offspring via increased intake of high-fat foods.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002641&type=printable |
| spellingShingle | Laura Dearden Isadora C Furigo Lucas C Pantaleão L W P Wong Denise S Fernandez-Twinn Juliana de Almeida-Faria Katherine A Kentistou Maria V Carreira Guillaume Bidault Antonio Vidal-Puig Ken K Ong John R B Perry Jose Donato Susan E Ozanne Maternal obesity increases hypothalamic miR-505-5p expression in mouse offspring leading to altered fatty acid sensing and increased intake of high-fat food. PLoS Biology |
| title | Maternal obesity increases hypothalamic miR-505-5p expression in mouse offspring leading to altered fatty acid sensing and increased intake of high-fat food. |
| title_full | Maternal obesity increases hypothalamic miR-505-5p expression in mouse offspring leading to altered fatty acid sensing and increased intake of high-fat food. |
| title_fullStr | Maternal obesity increases hypothalamic miR-505-5p expression in mouse offspring leading to altered fatty acid sensing and increased intake of high-fat food. |
| title_full_unstemmed | Maternal obesity increases hypothalamic miR-505-5p expression in mouse offspring leading to altered fatty acid sensing and increased intake of high-fat food. |
| title_short | Maternal obesity increases hypothalamic miR-505-5p expression in mouse offspring leading to altered fatty acid sensing and increased intake of high-fat food. |
| title_sort | maternal obesity increases hypothalamic mir 505 5p expression in mouse offspring leading to altered fatty acid sensing and increased intake of high fat food |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002641&type=printable |
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