FGF21 mediates the associations between exercise, ageing and glucose regulation LeeShuen Yee BurnsStephen Francis NgKenneth StenselDavid ZhongLiang TanFrankie ChiaKar Ling FamKai Deng YapMargaret YeoKwee Poo YapEric Peng Huat LimChin Leong 2019 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.