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

Abstract

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.

Microbiome First Medicine in Health and Safety

“…Obesity is one of the major conditions that gives rise to a myriad of comorbid, inflammation driven, chronic diseases particularly as aging progresses [ 62 , 63 ]. Table 2 illustrates examples of 43 comorbid NCDs for obesity [ 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. The obese population carries one of the highest risks for multiple future NCDs of any disease-burdened cohort.…”

Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies

“…Such microglial plasticity is also supported by a time-course study performed in mice fed HFD for 1-28 days, in which hypothalamic microglia express different markers at different times, with an early increase in CD86 expression at 3 days on HFD, followed by a decrease in this pro-inflammatory marker concomitant with the overexpression of CD206 [175] and arginase-1 [176] at 7 days on HFD, and a final overexpression of MHC-II after 28 days on HFD [175]. Consistent with the upregulation of some microglial markers, many studies have reported that microglia from HFD-fed rodents display an amoeboid morphology with thickened processes in several brain regions [147,150,152,153,157,165,167,168,177]. Conversely, one study in which rats were exposed to free-choice high-fat high-sugar diet did not find morphological changes in microglia neither in the cortex nor in the hippocampus [178].…”