Unrestricted Ketogenic Diet Feeding Enhances Epithelial Ovarian Cancer Growth In Vivo
The ketogenic diet (KD) is hypothesized to impact tumor progression by altering tumor metabolism. In this study, we assessed the impact of an unrestricted KD on epithelial ovarian cancer (EOC) tumor growth, gene expression, and metabolite concentration in a mouse model. ID8 EOC cells, which were syn...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/12/2730 |
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| author | Mariam M. AlHilli Emily E. Rhoades Danielle Chau Surabhi Tewari Adrian Reich Alex Myers Daniel J. Lindner Justin D. Lathia Renliang Zhang Belinda Willard Gail Cresci Nathan A. Berger Ofer Reizes |
| author_facet | Mariam M. AlHilli Emily E. Rhoades Danielle Chau Surabhi Tewari Adrian Reich Alex Myers Daniel J. Lindner Justin D. Lathia Renliang Zhang Belinda Willard Gail Cresci Nathan A. Berger Ofer Reizes |
| author_sort | Mariam M. AlHilli |
| collection | DOAJ |
| description | The ketogenic diet (KD) is hypothesized to impact tumor progression by altering tumor metabolism. In this study, we assessed the impact of an unrestricted KD on epithelial ovarian cancer (EOC) tumor growth, gene expression, and metabolite concentration in a mouse model. ID8 EOC cells, which were syngeneic with C57Bl/6J mouse strain and transfected with luciferase (ID8-luc), were injectedand monitored for tumor development. Female mice were fed either a strict KD, a high fat/low carbohydrate (HF/LC) diet, or a low fat/high carbohydrate (LF/HC) diet (n = 10 mice per group) ad libitum. EOC tumor growth was monitored weekly, and tumor burden was determined based on luciferase fluorescence (photons/second). At the endpoint (42 days), tumors were collected and processed for RNA sequencing. Plasma and tumor metabolites were evaluated using LC-MS. The KD-fed mice exhibited a statistically significant increase in tumor progression in comparison to the HF/LC- and LF/HC-fed groups (9.1 vs. 2.0 vs. 3.1-fold, respectively, <i>p</i> < 0.001). The EOC tumors of the KD-fed mice exhibited significant enrichment of the peroxisome proliferator-activated receptor (PPAR) signaling and fatty acid metabolism pathways based on the RNA sequencing analysis when compared to the LF/HC- and HF/LC-fed mice. Thus, unrestricted KD diet enhanced tumor progression in our mouse EOC model. KD was associated with the upregulation of fatty acid metabolism and regulation pathways, as well as enrichment of fatty acid and glutamine metabolites. |
| first_indexed | 2024-03-11T02:05:51Z |
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| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T02:05:51Z |
| publishDate | 2023-06-01 |
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| series | Nutrients |
| spelling | doaj.art-faac75313c1245f182211d05d8299f172023-11-18T11:56:47ZengMDPI AGNutrients2072-66432023-06-011512273010.3390/nu15122730Unrestricted Ketogenic Diet Feeding Enhances Epithelial Ovarian Cancer Growth In VivoMariam M. AlHilli0Emily E. Rhoades1Danielle Chau2Surabhi Tewari3Adrian Reich4Alex Myers5Daniel J. Lindner6Justin D. Lathia7Renliang Zhang8Belinda Willard9Gail Cresci10Nathan A. Berger11Ofer Reizes12Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Cleveland Clinic, Cleveland, OH 44195, USADepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44196, USADepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, Cleveland Clinic, Cleveland, OH 44195, USADepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44196, USADepartment of Bioinformatics, Florida Research and Innovations Center, Cleveland Clinic, Port St. Lucie, FL 34987, USADepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44196, USACase Comprehensive Cancer Center, Cleveland, OH 44106, USADepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44196, USAProteomics and Metabolic Core, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44196, USAProteomics and Metabolic Core, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44196, USADepartment of Gastroenterology, Hepatology and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH 44195, USACase Comprehensive Cancer Center, Cleveland, OH 44106, USADepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44196, USAThe ketogenic diet (KD) is hypothesized to impact tumor progression by altering tumor metabolism. In this study, we assessed the impact of an unrestricted KD on epithelial ovarian cancer (EOC) tumor growth, gene expression, and metabolite concentration in a mouse model. ID8 EOC cells, which were syngeneic with C57Bl/6J mouse strain and transfected with luciferase (ID8-luc), were injectedand monitored for tumor development. Female mice were fed either a strict KD, a high fat/low carbohydrate (HF/LC) diet, or a low fat/high carbohydrate (LF/HC) diet (n = 10 mice per group) ad libitum. EOC tumor growth was monitored weekly, and tumor burden was determined based on luciferase fluorescence (photons/second). At the endpoint (42 days), tumors were collected and processed for RNA sequencing. Plasma and tumor metabolites were evaluated using LC-MS. The KD-fed mice exhibited a statistically significant increase in tumor progression in comparison to the HF/LC- and LF/HC-fed groups (9.1 vs. 2.0 vs. 3.1-fold, respectively, <i>p</i> < 0.001). The EOC tumors of the KD-fed mice exhibited significant enrichment of the peroxisome proliferator-activated receptor (PPAR) signaling and fatty acid metabolism pathways based on the RNA sequencing analysis when compared to the LF/HC- and HF/LC-fed mice. Thus, unrestricted KD diet enhanced tumor progression in our mouse EOC model. KD was associated with the upregulation of fatty acid metabolism and regulation pathways, as well as enrichment of fatty acid and glutamine metabolites.https://www.mdpi.com/2072-6643/15/12/2730ketone bodieshigh fat dietovarian cancermicetumor metabolismtumor progression |
| spellingShingle | Mariam M. AlHilli Emily E. Rhoades Danielle Chau Surabhi Tewari Adrian Reich Alex Myers Daniel J. Lindner Justin D. Lathia Renliang Zhang Belinda Willard Gail Cresci Nathan A. Berger Ofer Reizes Unrestricted Ketogenic Diet Feeding Enhances Epithelial Ovarian Cancer Growth In Vivo Nutrients ketone bodies high fat diet ovarian cancer mice tumor metabolism tumor progression |
| title | Unrestricted Ketogenic Diet Feeding Enhances Epithelial Ovarian Cancer Growth In Vivo |
| title_full | Unrestricted Ketogenic Diet Feeding Enhances Epithelial Ovarian Cancer Growth In Vivo |
| title_fullStr | Unrestricted Ketogenic Diet Feeding Enhances Epithelial Ovarian Cancer Growth In Vivo |
| title_full_unstemmed | Unrestricted Ketogenic Diet Feeding Enhances Epithelial Ovarian Cancer Growth In Vivo |
| title_short | Unrestricted Ketogenic Diet Feeding Enhances Epithelial Ovarian Cancer Growth In Vivo |
| title_sort | unrestricted ketogenic diet feeding enhances epithelial ovarian cancer growth in vivo |
| topic | ketone bodies high fat diet ovarian cancer mice tumor metabolism tumor progression |
| url | https://www.mdpi.com/2072-6643/15/12/2730 |
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