Obesity Prevents S-Adenosylmethionine-Mediated Improvements in Age-Related Peripheral and Hippocampal Outcomes

Background: Age predisposes individuals to a myriad of disorders involving inflammation; this includes stress-related neuropsychiatric disorders such as depression and anxiety, and neurodegenerative diseases. Obesity can further exacerbate these effects in the brain. We investigated whether an inexpensive dietary supplement, s-adenosylmethionine (SAMe), could improve age- and/or obesity-related inflammatory and affective measures in the hippocampus. Methods: Mice were placed on their diets at six weeks of age and then aged to 14 months, receiving SAMe (0.1 g/kg of food) for the final six weeks of the experiment. Prior to tissue collection, mice were tested for anxiety-like behaviors in the open field test and for metabolic outcomes related to type 2 diabetes. Results: SAMe treatment significantly improved outcomes in aged control mice, where fasting glucose decreased, liver glutathione levels increased, and hippocampal microglia morphology improved. SAMe increased transforming growth factor β-1 mRNA in both control mice, potentially accounting for improved microglial outcomes. Obese mice demonstrated increased anxiety-like behavior, where SAMe improved some, but not all, open field measures. Conclusions: In summary, SAMe boosted antioxidant levels, improved diabetic measures, and hippocampal inflammatory and behavioral outcomes in aged mice. The effects of SAMe in obese mice were more subdued, but it could still provide some positive outcomes for obese individuals dealing with anxiety and having difficulty changing their behaviors to improve health outcomes.