SUN-641 Adipose Tissue Response to Vitamin E Status in the Regulation of Whole-Body Homeostasis

Abstract Disclosure: E.L. Lieu: None. P. Saha: None. S.M. Hartig: None. The essential, fat-soluble nutrient vitamin E performs antioxidant properties by preventing lipid peroxidation in times of elevated free radical generation. Dietary vitamin E is absorbed in the intestine and packaged in lipid-carrying vesicles and undergoes preferential export by the liver in the form of α-tocopherol. Ultimately, 90% of α-tocopherol is stored in the lipid droplets of adipocytes and becomes rapidly mobilized during high oxidative stress conditions such as in traumatic burn or irradiation injuries. However, the regulation of vitamin E levels in chronic disease such as obesity or type 2 diabetes is less clear, and studies on human subjects evaluating the relationship between adiposity and circulating vitamin E levels yield conflicting results. Further, several attempts to improve metabolic outcomes in obesity or type 2 diabetes by vitamin E supplementation fail to achieve meaningful, clinical endpoints. Together, these knowledge gaps highlight how the modulation of vitamin E storage in fat and the mechanism of purposeful vitamin E release from adipose tissue remain poorly defined. Since vitamin E cannot be endogenously synthesized and is mostly stored in adipose tissue, we implemented an α-tocopherol stripped diet to study the impact of vitamin E demand on whole-body metabolism. We placed 6-week-old male mice on vitamin E deficient (VED) or control diet for 8 weeks and characterized whole-body metabolism using the comprehensive lab animal monitoring system (CLAMS) and conducted studies of glucose disposal. Despite observing nominal energy balance changes in the metabolic cages, fasting in VED mice strongly decreased adipose tissue mass, especially in gonadal white adipose tissue, compared to age-matched controls. In line with adipose tissue reduction, VED mice exhibited lower circulating leptin and displayed elevated serum free fatty acid levels which predicts a role for lipolysis in regulating tissue vitamin E stores. Vitamin E status also seemingly affected insulin sensitivity as VED mice had lower serum insulin but improved glucose tolerance. Interestingly, H&E staining and morphometry analysis revealed decreased villus length and crypt depth only in the proximal small intestine of VED mice compared to controls, a finding associated with decreased capacity for nutrient uptake and impaired stem cell turnover. These findings emphasize the importance of adipose tissue in regulating whole-body redox and glucose homeostasis, and future work will determine why and how certain fat depots respond to whole-body vitamin E demands. Presentation: Sunday, July 13, 2025