FGF21 mediates the associations between exercise, ageing and glucose regulation

Introduction: Ageing increases the prevalence of glucose intolerance, but exercise improves glucose homeostasis. The fibroblast growth factor 21 (FGF21)-adiponectin axis helps regulate glucose metabolism. However, the role of FGF21 in mediating glucose metabolism with ageing and exercise remains unknown. Purpose: This study examined whether FGF21 responses to a glucose challenge are associated with habitual exercise, ageing and glucose regulation. Methods: Eighty age- and sex-matched healthy individuals were assigned to young sedentary and active (≤36 years old, n=20 each group) and older sedentary and active (≥45 years old, n=20 each group) groups. Fasted and post-prandial blood glucose concentration and plasma concentration of insulin, FGF21 and adiponectin were determined during an oral glucose tolerance test (OGTT). Results: During the OGTT, glucose concentrations were 9% higher (p=0.008) and FGF21 concentrations were 58% higher (p=0.014) in the older than the younger group, independent of activity status. Active participants had 40% lower insulin concentration and 53% lower FGF21 concentration than sedentary participants, independent of age (all p<0.001). Adiponectin concentration during the OGTT did not differ by age (p=0.448) or activity status (p=0.611). Within the younger group, post-prandial glucose, insulin and FGF21 concentrations during the OGTT were lower in active than in sedentary participants. In the older group, only post-prandial insulin and FGF21 concentrations were lower in active participants. Conclusions: FGF21, but not adiponectin, response during the OGTT is higher in older than younger adults and lower in active than sedentary individuals. Exercise-associated reduction in OGTT glucose concentrations was observed in younger but not older adults.