Elevated FGF21 during insufficient sleep in active but not sedentary volunteers
Authors: Broussard Josiane L. , Morton Sarah J. , Marbas Emily M , Knauer Oliver A , Melanson Edward L , Wright Kenneth P. 
Published: June 2021

Insufficient sleep induces insulin resistance and is associated with an increased risk for developing obesity and cardiometabolic diseases, implicating sleep loss as a metabolic stressor. Fibroblast growth factor 21 (FGF21) is a hepatokine secreted in response to stress and is elevated in human obesity and diabetes. FGF21 expression can be induced by free fatty acid (FFA) activation of peroxisome proliferator‐activator receptor alpha. We previously reported that insufficient sleep results in elevated FFA; however, the impact of insufficient sleep on FGF21 has not been explored. In an ongoing study, we are comparing the effects of insufficient sleep on insulin sensitivity in physically active and inactive individuals to determine whether regular exercise attenuates the adverse effects of insufficient sleep. To explore the effects of physical activity and insufficient sleep on FGF21, we compared changes in FGF21 during an oral glucose tolerance test (OGTT).Eleven sedentary (SED: 6F, 24.9±4.2y, 22.3±1.7kg/m2; mean±SD) and 11 physically active adults (PA: 6F, 23.5±3.3y, 22.0±2.3kg/m2) participated in a 6‐day controlled inpatient protocol. Participants were provided isocaloric diets designed to meet energy requirements. Active participants continued to exercise during insufficient sleep by conducting 60 minutes of moderate physical activity (treadmill running) at 65–75% of maximum heart rate. An OGTT was conducted at baseline (9h sleep opportunity/night) and after 3 nights of insufficient sleep (5h sleep opportunity/night). Blood was sampled at T=0, +30, +60, +90, and +120 minutes following glucose ingestion and assayed for FGF21, glucose, insulin and FFA.FGF21 was elevated in response to insufficient sleep in PA participants (Fig 1a; baseline: 40.5±13.3 v. insufficient sleep: 95.3±18.2 pg/ml, p<0.05), but not SED (baseline: 68.9±19.4 v. insufficient sleep: 95.6±24.1 pg/ml, p=ns). Both SED and PA participants displayed elevated glucose in response to the OGTT during insufficient sleep (Fig 1b), whereas insulin was elevated only in SED participants (Fig 1c). PA participants had higher levels of FFA as compared to SED, though FFA were not altered by insufficient sleep in either group (Fig 1d). Changes in FGF21 were not related to glucose, insulin or FFA.FGF21 is elevated during insufficient sleep in physically active individuals. Furthermore, insulin response to an OGTT during insufficient sleep was attenuated only in the physically active participants. Though the physiological implications of elevated FGF21 in humans are unclear, we speculate that elevated FGF21 during insufficient sleep in active individuals may act as a compensatory response to mitigate metabolic impairments.Support or Funding InformationThis work was supported by the Sleep Research Society Early Career Development Award, the National Institutes of Health GCRC grant RR‐00036, R01HL109706 and K01DK110138, Society in Science, and The Branco Weiss Fellowship, administered by the ETH Zürich.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.