Dietary Poly Unsaturated Fatty Acid (pufa) Regulation of Organ and Tissue Microenvironments in an Iso-Caloric Pair-Fed Mouse Model

Abstract The majority of omega-3 (ω3) and ω3 PUFA diet studies have not differentiated dietary PUFA content from obesity. Our studies used pair-fed iso-caloric diets containing 35.5% of calories from fat with an ω6:ω3 ratio in ω6 and ω3 diets of 42:1 and 1:1 respectively with DeCarli diets and fish oil substituting for 70% of olive oil. The ω3 diet contained eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid at a 3:1 ratio, while the ω6 diet contained linoleic acid and a low level of linolenic acid. Female BALB/c mice were monitored for weight gain, diet consumption and sacrificed (12 wks) to examine mammary gland, spleen, bone and hepatic histopathology, leukocyte phenotypes and organ and tissue lipidomics. In association with pair feeding there were no differences in diet consumed and weight gain. The ω6 cohort had decreased numbers of progenitor cells and an increase in splenic subcapsular extramedullary hematopoiesis and hepatocyte lipidosis, hypertrophy and multinucleation and increased hepatic vascularity with thicker intima. The ω-6 cohort also had mammary fat pads (MFPs) with increased adipocytes in the tubular epithelium, stromal cellularity and epithelial tissue density. These changes and subclinical inflammation were accompanied by organ specific lipodemic changes, including increases in arachidonic acid (AA) in the plasma, spleen and liver, but not MFPs, of the ω-6 mice, and an increase in EPA and DHA in the plasma, spleen, MFPs and liver of the ω-3 mice. Further, B and T cells and macrophages had an increase in the % of phospho NFκβ+ cells and the liver and MFPs had an increase in the ω3 PUFA, docosapentaenoic acid. In summary, the dietary ω6:ω3 ratio, independent of obesity, regulates mammary gland, spleen and hepatic inflammation.