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Metabolic and Metabolomic Effects of Metformin in Murine Model of Pulmonary Adenoma Formation
Andrew C Elton1, Vannesa Cedarstrom1, Arman Quraishi1
1Department of Otolaryngology - Head and Neck Surgery, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Abstract:
Epidemiologic studies of diabetic patients treated with metformin identified significantly lower incidences of cancer. From this, there is growing interest in the use of metformin to treat and prevent cancer. Studies have investigated chemopreventive mechanisms including alterations in calorie intake, cancer metabolism, and cell signaling. Repurposing the drug is challenging due to its metabolic effects and non-uniform effects on different types of cancer. In our previously published studies, we observed that benzo[a]pyrene treated mice receiving metformin significantly reduced lung adenomas; however, mice had reduced weight gain. In this study, we compared chemoprevention diets with and without metformin to evaluate the effects of diet vs. effects of metformin. We also performed tandem mass spectrometry on mouse serum to assess metabolomic alterations associated with metformin treatment. In metformin cohorts, the rate of weight gain was reduced, but weights did not vary between diets. There was no weight difference between diets without metformin. Interestingly, caloric intake was increased in metformin treated mice. Metabolomic analysis revealed metabolite alterations consistent with metformin treatment. Based on these results, we conclude that previous reductions in lung adenomas may have been occurred from anticancer effects of metformin rather than a potentially toxic effect such as calorie restriction.
Insights
Metformin shows promise in cancer prevention by directly targeting cancer cells, not just by reducing calorie intake. This study differentiates metformin's anticancer effects from potential side effects like weight loss.
Area of Science:
- Oncology
- Pharmacology
- Metabolomics
Background:
- Epidemiologic studies suggest metformin use in diabetic patients is linked to lower cancer incidence.
- Metformin is being investigated for cancer treatment and prevention, with proposed mechanisms involving metabolic and signaling pathways.
- Previous research indicated metformin reduced lung adenomas in mice but also caused weight reduction.
Purpose of the Study:
- To differentiate the direct anticancer effects of metformin from dietary effects in cancer chemoprevention.
- To investigate the impact of metformin on weight gain and caloric intake in a mouse model.
- To identify metabolomic alterations associated with metformin treatment using tandem mass spectrometry.
Main Methods:
- Comparison of chemoprevention diets with and without metformin in a mouse model.
- Assessment of weight gain and caloric intake across different treatment groups.
- Tandem mass spectrometry analysis of mouse serum to evaluate metabolomic changes.
Main Results:
- Metformin treatment reduced the rate of weight gain but did not affect final body weight.
- Caloric intake was increased in metformin-treated mice, contradicting a calorie restriction mechanism.
- Metabolomic analysis revealed significant alterations consistent with metformin's known metabolic effects.
Conclusions:
- The observed reduction in lung adenomas is likely due to metformin's direct anticancer properties.
- Metformin's chemopreventive effects are not solely attributable to calorie restriction or associated weight loss.
- Metformin exhibits distinct metabolic alterations supporting its potential as an anticancer agent.
