MON-678 - Polyunsaturated Fatty Acids Uncover Vitamin E-Driven Adipose Tissue Responses

Vitamin supplementation is widely endorsed for its accessibility and safety but is often used without strong scientific or clinical evidence of efficacy. The fat-soluble vitamin E (VE) performs antioxidant properties by preventing lipid peroxidation in times of elevated free radical generation. Hypermetabolic states, such as burn injury and irradiation, can rapidly reduce VE in adipose tissue which serves as the storage site for 90% of VE. However, several studies on human subjects evaluating the relationship between adiposity and circulating or stored VE levels in chronic diseases such as obesity or type 2 diabetes yield conflicting and poorly elaborated results. Therefore, attempts to improve metabolic outcomes by VE supplementation never materialized. Together, these knowledge gaps highlight how the regulation of VE storage in fat and the mechanism of purposeful VE release from adipose tissue remain poorly defined. To model increasing physiological VE demand and impacts on whole-body metabolism, I placed mice on flaxseed oil-based vitamin E deficient (VED) and corresponding control diet containing supplemented VE. Importantly, flaxseed oil contains a high percentage of polyunsaturated fatty acids (PUFA). A major source of lipid peroxides is PUFA, and studies have shown the importance of raising VE levels when faced with higher PUFA content to lower oxidative stress. To test the prediction that PUFA content in the flaxseed-based diets are a stimulus that can unveil adipose tissue responses to high VE demand, I also performed the studies with a lard-based VED and control diet, which have much lower levels of PUFA. Overnight fasting in flaxseed-VED mice strongly decreased adipose tissue mass, especially in gonadal white adipose tissue, compared to age-matched controls. In line with adipose tissue reduction, flaxseed-VED mice exhibited lower circulating leptin and had elevated serum free fatty acid levels which predicts a role for lipolysis in regulating tissue VE stores. Using a fluorescent VE analog, I identified VE is stored within the lipid droplets of adipocytes. I then activated beta-adrenergic signaling to induce lipolysis in differentiated mouse fibroblasts which was sufficient to reduce BODIPY-labeled lipid content in differentiated adipocytes but was unable to deplete VE from the lipid droplets. This indicates that VE release is independent of other lipid species. Interestingly, the changes observed in the flaxseed diet group were absent in the lard-VED group, despite both VED groups demonstrating over 95% reduction in circulating VE. These findings emphasize the importance of adipose tissue in responding to VE status, and future work will identify signals for specified VE release from adipose tissue. Understanding these mechanisms has clinical implications for adipose tissue nutrient handling and may identify regulatory pathways shared by other fat-soluble nutrients.

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