Related Experiment Video
Updated: Aug 6, 2025
Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice
Published on: November 27, 2019
Intermittent Fasting induced ketogenesis inhibits mouse epithelial ovarian tumors by promoting anti-tumor T cell
Mary Priyanka Udumula1, Harshit Singh1, Rashid Faraz2
1Department of Women's Health Services, Henry Ford Hospital and Henry Ford Cancer Institute, Detroit, MI.
Abstract:
Epithelial Ovarian Cancer (EOC) is the most lethal gynecologic cancer with limited genetic alterations identified that can be therapeutically targeted. In tumor bearing mice, short-term fasting, fasting mimicking diet and calorie restriction enhance the activity of antineoplastic treatment by modulating systemic metabolism and boosting anti-tumor immunity. We tested the outcome of sixteen-hour intermittent fasting (IF) on mouse EOC progression with focus on fasting driven antitumor immune responses. IF resulted in consistent decrease of tumor promoting metabolic growth factors and cytokines, recapitulating changes that creates a tumor antagonizing environment. Immune profiling revealed that IF profoundly reshapes anti-cancer immunity by inducing increase in CD4+ and CD8+ cells, paralleled by enhanced antitumor Th1 and cytotoxic responses, by enhancing their metabolic fitness. Metabolic studies revealed that IF generated bioactive metabolite BHB which can be a potential substitute for simulating the antitumor benefits of IF. However, in a direct comparison, IF surpassed exogenous BHB therapy in improving survival and activating anti-tumor immune response. Thus, our data provides strong evidence for IF and its metabolic mediator BHB for ameliorating EOC progression and as a viable approach in maintaining and sustaining an effective anti-tumor T cell response.
Insights
Intermittent fasting (IF) effectively combats epithelial ovarian cancer (EOC) in mice by enhancing anti-tumor immunity and creating a less hospitable tumor environment. This fasting approach, along with its metabolite BHB, shows promise for EOC treatment.
Area of Science:
- Oncology
- Immunology
- Metabolism
Background:
- Epithelial ovarian cancer (EOC) is a highly lethal gynecologic malignancy with limited targeted therapeutic options.
- Metabolic interventions like fasting have shown potential in enhancing anti-cancer treatments by modulating systemic metabolism and immunity.
Approach:
- Investigated the impact of 16-hour intermittent fasting (IF) on mouse EOC progression, focusing on IF-driven anti-tumor immune responses.
- Analyzed metabolic and immune profiles to understand the mechanisms underlying IF's effects.
- Compared the efficacy of IF with its bioactive metabolite, beta-hydroxybutyrate (BHB).
Key Points:
- Intermittent fasting (IF) reduced tumor-promoting metabolic factors and cytokines, creating a tumor-antagonizing environment.
- IF significantly increased CD4+ and CD8+ T cells, enhancing anti-tumor Th1 and cytotoxic responses by improving T cell metabolic fitness.
- The metabolite beta-hydroxybutyrate (BHB) generated by IF showed potential but was less effective than IF itself in improving survival and immune response.
Conclusions:
- Intermittent fasting (IF) demonstrates significant potential in ameliorating epithelial ovarian cancer (EOC) progression.
- IF enhances anti-tumor immunity and T cell responses, offering a viable therapeutic strategy.
- The metabolite BHB may partially mediate IF's benefits, but IF itself provides superior anti-cancer effects.
