Diet-induced increases in chemerin are attenuated by exercise and mediate the effect of diet on insulin and HOMA-IR

Objectives: Chemerin concentrations are elevated in obesity and associated with inflammation and insulin resistance. Exercise improves insulin sensitivity, which may be facilitated by changes in chemerin. We explored the effects of chronic exercise on chemerin levels in diet-induced obese mice. Methods: We divided 40 mice into 4 groups: high-fat diet/exercise, high-fat diet/sedentary, normal diet/exercise, and normal diet/sedentary. A 9-week dietary intervention was followed by a 12-week exercise intervention (treadmill run: 11 m/min for 30 min, 3x/week). We analyzed blood samples before and after the exercise intervention. We used t-tests and linear regression to examine changes in chemerin, insulin resistance, and inflammatory markers, and associations between changes in chemerin and all other biomarkers. Results: Chemerin increased significantly across all mice over the 12-week intervention (mean +/- SD = 40.7 +/- 77.8%, p = 0.01), and this increase was smaller in the exercise versus sedentary mice (27.2 +/- 83.9% versus 54.9 +/- 70.5%, p = 0.29). The increase among the high-fat diet/exercise mice was similar to 44% lower than the increase among the high-fat diet/sedentary mice (55.7 +/- 54.9% versus 99.8 +/- 57.7%, p = 0.12). The high-fat diet mice showed significant increases in insulin (773.5 +/- 1286.6%, p < 0.0001) and homeostatic model assessment of insulin resistance (HOMA-IR; 846.5 +/- 1723.3%, p < 0.01). Mediation analyses showed that increases in chemerin explained a substantial amount of the diet-induced increases in insulin and HOMA-IR. Conclusion: Chronic exercise may attenuate diet-driven increases in circulating chemerin, and the insulin resistance associated with a high-fat diet may be mediated by diet-induced increases in chemerin.