Meal-feeding promotes skeletal growth by ghrelin-dependent enhancement of growth hormone rhythmicity.

Summary

Across rodents and humans, structured meal-feeding induced preprandial ghrelin surges and tripled GH secretion by increasing burst height and frequency, sustaining skeletal growth despite reduced intake. Continuous enteral feeding sustained ghrelin and flattened GH rhythmicity, while bolus feeding enhanced ultradian GH rhythms. Findings challenge grazing/snacking behavior as optimal for growth, implicating ghrelin-GHS-R–dependent GH pulsatility as a key mediator.

Key Findings

• Meal-feeding induced preprandial ghrelin surges and tripled GH secretion via increased burst height with two additional daily GH bursts.
• Rodent skeletal growth (body length and tibial epiphyseal plate width) was maintained in meal-fed animals through ghrelin/GHS-R signaling despite reduced caloric intake.
• In humans, continuous enteral feeding sustained ghrelin and minimized GH rhythmicity, whereas bolus enteral feeding restored ultradian GH rhythms with postprandial ghrelin troughs.

Clinical Implications

Structured meal timing may optimize GH pulsatility and growth, informing dietary counseling in pediatrics and potentially augmenting GH therapies; however, interventional trials on growth outcomes are needed before guideline changes.

Limitations

• Human experiments were short-term physiological studies without growth outcomes
• Rodent studies used males; generalizability to females, children, and clinical populations remains to be tested

Future Directions

Randomized trials testing meal timing interventions on longitudinal growth and GH therapy response; mechanistic dissection of downstream targets of GH pulses on growth plates in humans.