Abstract 13651: Adipose Tissue Resolvin Biosynthesis is Abrogated by High Fat Diet-Induced Adrenergic Deficiency

Diet-induced chronic inflammation in adipose tissue (AT) is associated with systemic insulin resistance. Conversely, exercise (Exe) protects against the development of chronic inflammation and insulin resistance. Our lab recently showed that exercise promotes inflammation resolution through adrenergic stimulation of specialized proresolving mediators (SPMs). In this study, we sought to determine if the proresolving benefits of exercise were dietary dependent. When compared with sedentary controls (Sed), mice exposed to 4 wk of Exe display elevated AT expression of SPM biosynthetic enzyme Alox15 (Sed 1.12±0.18 vs. Exe 1.68±0.13 relative expression, n =5-7), SPM levels (Sed vs. Exe; RvD1 156.7±12.02 vs. 223.0±24.71; 17 R -RvD1 354.0±35.86 vs. 534.4±98.92; RvD4 31.31±6.93 vs. 123.1±30.69; and 17 R -RvD3 2.92±1.08 vs. 8.20±1.70 pg/g, n =5-7), and anti-inflammatory macrophages (F4/80 + CD301 + ; Sed 17.5±3.2 vs. Exe 40.9±4.5 %F4/80 + , n =4-6). These changes were dependent upon diet as short duration feeding with high fat diet (60% kcal from fat; HFD) abrogated the proresolving effect of exercise when compared with low fat diet (10% kcal from fat; LFD) controls. Interestingly, exercise-induced epinephrine (Epi) production in LFD-fed mice (Sed 147.2±24.4 vs Exe 312.5±60.9 ng/mL) was inhibited by HFD (Sed 121.1±22.7 vs. Exe 140.0±16.8 ng/mL). HFD feeding resulted in diminished expression of the Epi biosynthetic enzyme phenylethanolamine N-methyltransferase (PNMT) in adrenal glands when compared with LFD fed animals (protein expression: LFD 1.0±0.25 vs. HFD 0.36±0.15, n =4). These results suggest that the proresolving effects of exercise in adipose tissue are dietary and adrenergic dependent.