Effects of Short-term Fasting on Ghrelin/GH/IGF-1 Axis in Healthy Humans:The Role of Ghrelin in the Thrifty Phenotype

Context: A greater decrease in 24-hour energy expenditure (24hEE) during short-term fasting is indicative of a thrifty phenotype. Objective: As ghrelin and the growth hormone IGH)/insulin-like growth factor 1 (IGF-1) axis are implicated in the regulation of energy intake and metabolism, we investigated whether ghrelin, GH, and IGF-1 concentrations mediate the fasting-induced decrease in 24hEE that characterizes thriftiness. Methods: In 47 healthy individuals, 24hEE was measured in a whole-room indirect calorimeter both during 24-hour eucaloric and fasting conditions. Plasma total ghrelin, GH, and IGF-1 concentrations were measured by enzyme-linked immunosorbent assay after an overnight fast the morning before and after each 24-hour session. Results: During 24-hour fasting, on average 24hEE decreased by 8.0% (P < .001), GH increased by similar to 5-fold (P < .001), whereas ghrelin (mean +23 pg/mL) and IGF-1 were unchanged (both >= .19) despite a large interindividual variability in ghrelin change (SD 150 pg/mL). Greater fasting-induced increase in ghrelin was associated with a greater decrease in 24hEE during 24-hour fasting (r = -0.42, P = .003), such that individuals who increased ghrelin by 200 pg/mL showed an average decrease in 24hEE by 55 kcal/day. Conclusion: Short-term fasting induced selective changes in the ghrelin/GH/IGF-1 axis, specifically a ghrelin-independent GH hypersecretion that did not translate into increased IGF-1 concentrations. Greater increase in ghrelin after 24-hour fasting was associated with greater decrease in 24hEE, indicating ghrelin as a novel biomarker of increased energy efficiency of the thrifty phenotype.

Automated summary

This study investigates the role of ghrelin, GH, and IGF-1 in the fasting-induced decrease in 24-hour energy expenditure (24hEE). The results show that fasting leads to an increase in GH, while ghrelin and IGF-1 remain unchanged. The increase in ghrelin after fasting is associated with a decrease in 24hEE, suggesting that ghrelin may serve as a novel biomarker of increased energy efficiency in the thrifty phenotype.