Vitamin B1 Supplementation Ameliorates Obesogenic Effects of a High Fat Diet in Male Mice

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 hypothesized that the concurrent malnutrition caused by a soybean oil-based high fat diet (SO-HFD) and a physiological deficiency in thiamine can exacerbate conditions such as obesity, diabetes, and fatty liver that are associated with consumption of HFDs. To test this, C57BL/6N male mice (N=8-10 per group) were fed either a low-fat chow or an SO-HFD, with or without supplementation with 640 mg/kg of the thiamine analog thiamine tetrahydrofurfuryl disulfide (TTFD), for 18 weeks. Our results showed that the SO-HFD supplemented with TTFD leads to significantly decreased weight gain and delayed the onset of glucose intolerance compared to SO-HFD without added TTFD (p<0.05). In contrast, TTFD supplementation did not have any effect on body weight or glucose intolerance in the context of a low-fat diet. Metabolomic analysis revealed that the SO-HFD decreased absolute thiamine levels both in the blood and liver tissue compared to the low fat control diet (p<0.05); this decrease was reversed by TTFD supplementation suggesting that some of the negative effects of the SO-HFD may be due to its impact on the Vitamin B1 pathway. Untargeted metabolomic analysis identified several other metabolites — such as amino acids, organic acids, methylamine osmolytes and those involved in nucleotide metabolism — that were also affected by TTFD supplementation, but in a beneficial fashion. Transcriptomic analysis of the liver and intestines revealed alterations in thiamine absorption and metabolic pathways by the SO-HFD; effects of TTFD on hepatic gene expression and fatty liver will be presented. TTFD supplementation given after the onset of SO-HFD-induced obesity was not able to reverse the phenotype, suggesting that the deleterious effects of the SO-HFD-induced Vitamin B1 deficiency may be permanent. In conclusion, our findings indicate that consumption of an SO-enriched diet, similar in fat content to what is consumed by most Americans, can result in a Vitamin B1 deficiency. Although TTFD supplementation may mitigate some of the adverse metabolic effects of this diet, this intervention must be done at an early stage. Funding: The Thiamine Advocacy Foundation Research Grant (FMS, PHD, PD); NIH R01DK127082 (FMS)Acknowledgements: UCR Genomics Core Facility, UCR Metabolomics Core Facility, UCR High Performance Computing Center (HPCC). 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.