Abstract

Dietary deficiencies in vitamins such as thiamine (Vitamin B1) are common even in developed countries and can have a range of deleterious health effects. This trend in Vitamin B1 deficiency coincides with increased fat consumption in the American diet, particularly of soybean oil, the most widely consumed cooking oil in the U.S. which is also present in many processed foods. Here, we hypothesize that the concurrent malnutrition caused by a soybean oil-based high fat diet (SO-HFD) and a physiological deficiency in thiamine can impact regional gene expression in the brain and behavior. To test this, C57BL/6N male mice (N=10-12 per group) were fed either a low-fat chow (OSD) or an SO-HFD, with or without supplementation with 640 mg/kg of the thiamine analog thiamine tetrahydrofurfuryl disulfide (TTFD), for 18 weeks. Mice were subjected to a series of behavioral tests designed to evaluate cognition (passive avoidance test, PAT), strength (modified grip strength test, MGS), exercise endurance (treadmill test, EE), and locomotor/habituation activity (open field test, OFT). Our results showed no difference across groups on the PAT. On the MGS test, the force generated when normalized to body weight was lesser on all test days for SO-HFD as compared to OSD (p<0.05-0.0001). The TTFD supplementation improved MGS only in the SO group (p<0.05). On EE, OSD ran significantly longer before exhaustion as compared to SO (p<0.05-0.001). For one subset of animals TTFD supplementation improved the EE score in SO but not OSD (p<0.05-0.001). During the one-hour OFT, distance traveled decreased over time for both TTFD-supplemented groups only (p<0.05-0.01), indicating improvement in habituation/learning. Transcriptomic analysis of the hypothalamus and hippocampus from these mice revealed differentially expressed genes (p<0.05) that may contribute to alterations observed in the behavioral tests. Our results indicate that TTFD supplementation ameliorates HFD-induced deficits in strength and exercise endurance. TTFD supplementation improved habituation/learning on OFT regardless of diet. The Thiamine Advocacy Foundation, NIH R01DK127082 (FMS), DOD GW180072 (MCC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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