Gut Hormones and Hypothalamic Pituitary Integration in Linear Growth and Weight Regulation in Children and Adolescents

Abstract

Background: Gut peptides coordinate food intake, nutrient handling and neuroendocrine responses during development. Their relevance to paediatric obesity is established more firmly than their contribution to attained height. Recent receptor genetics, incretin trials and nutritional interventions justify an integrated reassessment. Objective: To examine relationships between gut hormones, hypothalamic–pituitary signalling, linear growth and weight trajectories, distinguish causal evidence from association, and identify diagnostic and therapeutic implications. Methods: A structured, targeted narrative synthesis evaluated PubMed-indexed publications dated January 2001 to 10 September 2026. Bibliographic records and available abstracts were verified against PubMed-linked Europe PMC records. Paediatric systematic reviews and randomised trials received greatest weight, followed by cohorts, genetic and functional studies, and case reports. Adult and experimental findings were explicitly separated. Direct Scopus searching, exhaustive screening, independent duplicate selection and formal risk-of-bias grading were not performed. Results: GLP-1 receptor agonists have the strongest paediatric interventional evidence for reducing excess weight gain and BMI. GHSR loss-of-function variants strengthen the biological link between ghrelin signalling and stature, including short stature with low IGF-I despite normal conventional stimulated GH responses. Circulating ghrelin does not consistently predict height velocity. Undernutrition can uncouple GH secretion from IGF-I production. GLP-2 treatment supports intestinal adaptation, although height responses are heterogeneous. Microbiota-directed nutrition offers encouraging growth evidence in young undernourished children, without establishing gut-hormone mediation. Long-term effects of incretin therapy on adult height and peak bone mass remain insufficiently characterised. Conclusions: Gut signals influence both energy balance and the conditions permitting growth, but weight efficacy cannot establish linear-growth efficacy. Clinical interpretation requires attention to nutritional state, puberty, receptor function and the specific outcome measured.