Unacylated ghrelin is associated with changes in insulin sensitivity and lipid profile during an exercise intervention

OBJECTIVE: Ghrelin has been implicated in energy homeostasis, body weight regulation and glucose metabolism. Level of unacylated ghrelin (UAG), but not acylated ghrelin (AG), has been suggested to increase during long-term exercise. However, the association of the level of UAG with exercise-induced changes of insulin sensitivity and lipid metabolism has not been previously investigated. We hypothesized that an increase in UAG level in response to a long-term exercise programme improves insulin sensitivity and associated lipid profile, independently of weight loss. DESIGN, PATIENTS AND MEASUREMENTS: A prospective study of 552 young men (mean age 19·3 and range 19-28 years) undergoing military service with structured 6-month exercise training programme. Exercise performance, clinical and biochemical measurements were obtained at baseline and follow-up. Association between UAG level and fasting glucose, insulin, insulin sensitivity and lipid levels were evaluated. RESULTS: An overall increase in the level of UAG was observed during the 6-month follow-up (P < 0·001), which was largest among those with weight loss ≥ 2·5% or among those whose reduction in waist circumference was largest (P = 0·007 and P < 0·001, respectively). A change in UAG level correlated inversely with a change in fasting glucose and insulin levels, HOMA-IR, total cholesterol and total triglyceride levels (P < 0·001 for all). The association between change in the UAG level and the change in insulin sensitivity was independent of weight loss or reduction in waist circumference. CONCLUSIONS: Increase in UAG level was associated with improved insulin sensitivity via mechanisms independent of weight loss during an intensive, long-term exercise intervention in young healthy men.