Exercise-Stimulated Resolvin Biosynthesis in the Adipose Tissue Is Abrogated by High-Fat Diet-Induced Adrenergic Deficiency

BACKGROUND: Diet-induced white adipose tissue inflammation is associated with insulin resistance and metabolic perturbations. Conversely, exercise protects against the development of diet-induced chronic inflammation and insulin resistance independent of weight loss; however, the mechanisms remain largely unknown. We have recently shown that through adrenergic stimulation of macrophages, exercise promotes resolution of acute peritoneal inflammation by enhancing the biosynthesis of specialized proresolving lipid mediators. In this study, we sought to determine whether exercise stimulates proresolving pathways in adipose tissue and whether this response is modified by diet. Specifically, we hypothesized that exercise stimulates proresolving pathways by adrenergic signaling, which is inhibited by high-fat diet, priming the development of chronic inflammation in the adipose tissue. METHODS: To explore the dietary dependence of the proresolving effects of exercise, mice were fed either a control or high-fat diet for 2 weeks before, and throughout, a 4-week period of daily treadmill running. Glucose handling, body weight and composition, lipemia, and exercise performance were evaluated at the end of the feeding and exercise interventions. Likewise, changes in catecholamines and their biosynthetic enzymes were measured along with adipose tissue specialized proresolving lipid mediator levels and macrophage phenotype and abundance. RESULTS: When compared with sedentary controls, macrophages isolated from mice exposed to 4 weeks of exercise display elevated expression of the specialized proresolving lipid mediator biosynthetic enzyme Alox15, while adipose tissue specialized proresolving lipid mediator levels and anti-inflammatory CD301(+) M2 macrophages increased. These changes were dependent upon diet as 6 weeks of feeding with high-fat diet abrogated the proresolving effect of exercise when compared with control diet-fed animals. Interestingly, exercise-induced epinephrine production was inhibited by high-fat diet, which diminished the expression of the epinephrine biosynthetic enzyme PNMT (phenylethanolamine N-methyltransferase) in adrenal glands. CONCLUSIONS: Taken together, these results suggest that a diet high in fat diminishes the proresolving effects of exercise in the adipose tissue via decreasing the biosynthesis of catecholamines.