A peroxidized omega-3-enriched polyunsaturated diet leads to adipose and metabolic dysfunction

February 1, 2019

Journal of Nutritional Biochemistry. 2019 Feb;64:50-60

 James L. Miller, Magdalena Blaszkiewicz, Cordell Beaton, Cory P. Johnson, Stephen Waible II,

Amanda L. Dubois, Amanda Klemmer, Michael A. Kiebish, Kristy L. Townsend

Consumption of diets that differ in fat type and amount, and sequestration of various fatty acids to tissues and organs likely have effects on overall physiology and metabolic health. However, the contributions of dietary lipids to brain–adipose communication and adipose tissue function are poorly understood.We designed six custom diets that differed only in amount and type of dietary fat,with high or lowlevels of saturated fatty acids (SFA), omega-6 polyunsaturated fatty acids (n-6 PUFA) or omega-3 (n-3) PUFA. Mice fed the n-3 PUFA diet for 16weeks displayed a striking reduction inweight gain accompanied by smaller adipose depots and improved glucose sensitivity. Reduced body weight occurred despite lowered energy expenditure and no difference in food intake. Despite the apparent beneficial effects towhole body physiology, we have demonstrated for the first time that a peroxidized n-3-enriched diet led to lipotoxicity of white adipose tissue, as evidenced by increased fibrosis, lipofuscin, reduced anti-inflammatorymarkers and loss of proper nerve supply. While healthful, n-3 fats are prone to peroxidation, andwe observed peroxidated lipidmetabolites in the adipose tissue of mice on these diets. Furthermore, using a lipidomics approach, we have observed that brain, white adipose tissue and brown adipose tissue accumulate lipid metabolites differently. The brain remainedmostly shielded fromchanges in dietary fat type and amount, but differences in adipose lipidmetabolites across these six diets may have affected metabolic function and brain–adipose communication, as observed in this study.

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