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)

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at