Adipose tissue (AT) inflammation is associated with obesity-induced insulin resistance. Exercise (Exe) prevents the development of chronic inflammatory diseases and insulin resistance largely through unknown mechanisms. We sought to determine if changes in specialized pro-resolving lipid mediators (SPM) in AT contribute to the anti-inflammatory effect of exercise. When compared with sedentary controls (Sed), normal chow fed mice exposed to 4 wk of Exe showed 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; 17R-RvD1 354.0±35.86 vs. 534.4±98.92; RvD4 31.31±6.93 vs. 123.1±30.69; and 17R-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 diet-dependent as feeding with high fat diet (60% kcal from fat; HFD) abrogated the pro-resolving effect of exercise in AT when compared with low fat diet (10% kcal from fat; LFD) controls. Exercise-stimulated upregulation of 15-LO expression was localized to AT macrophages in a diet-dependent manner (LFD Sed 0.11±0.03 vs. LFD Exe 0.23±0.03; HFD Sed 0.10±0.04 vs. HFD Exe 0.08±0.02 relative expression, n=3-6), as adipocytes from exercised mice showed no difference in 15-LO expression compared with sedentary controls. Given that epinephrine stimulates macrophage 15-LO expression and RvD1 production, we questioned if catecholamine biosynthesis was affected by HFD feeding. Adrenal glands from mice fed HFD show diminished expression of phenylethanolamine N-methyltransferase when compared with controls (LFD 1.0±0.25 vs. HFD 0.36±0.15, n=4). Similarly, db/db mice also displayed reduced catecholamines and expression of biosynthetic enzymes in the adrenal glands.
These results suggest that obesity-induced adrenergic dysfunction abrogates exercise-stimulated resolvin production in AT.
J. Hellmann: None. W. Lynch: None. E.P. Calderin: None. B. Sansbury: None. M. Spite: None. A. Bhatnagar: None. B. Hill: None.
American Diabetes Association (1-16-JDF-041 to B.H.); National Institutes of Health (GM127495, GM127607)