Clinical nutrition ESPEN · 2026
Insights into Natural Dietary Components as Indirect Modulators of Glucagon-like Peptide-1 Receptor Signaling in Weight Management.
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Ramasinghe Chapa, Xu Baojun
Аннотация
BACKGROUND: The glucagon-like peptide-1 receptor (GLP-1R) has emerged as a major therapeutic target in obesity and metabolic disease due to its roles in appetite regulation, gastric emptying, insulin secretion, and energy homeostasis. Although pharmacological GLP-1R agonists produce substantial weight reduction and glycemic improvement, growing interest has focused on natural dietary components capable of indirectly enhancing endogenous glucagon-like peptide-1 (GLP-1) signaling.
SCOPE: This review critically examines current mechanistic and translational evidence regarding dietary proteins, fermentable carbohydrates, dietary lipids, and phytochemical-rich foods as indirect modulators of GLP-1R activity in weight management.
KEY FINDINGS: Unlike synthetic agonists that directly bind and activate GLP-1R, dietary components primarily act through upstream nutrient-sensing and enteroendocrine pathways, including free fatty acid receptors (FFARs), the calcium-sensing receptor (CaSR), and Takeda G protein-coupled bile acid receptor 1 (TGR5), while additional mechanisms involve gut microbiota modulation, short-chain fatty acid production, delayed gastric emptying, and partial inhibition of dipeptidyl peptidase-4 (DPP-4). Evidence from clinical, preclinical, and translational studies demonstrates that dietary interventions can enhance endogenous GLP-1 secretion, improve satiety, reduce postprandial glycaemia, and support modest weight reduction. However, responses remain variable and generally less potent than pharmacological GLP-1R agonism CONCLUSION: Collectively, current findings support natural dietary components as physiologically relevant indirect modulators of GLP-1R signaling that may complement pharmacological therapies and contribute to sustainable long-term weight management. Further well-controlled human studies are required to clarify receptor-specific mechanisms, optimize dietary strategies, and strengthen translational applicability.
SCOPE: This review critically examines current mechanistic and translational evidence regarding dietary proteins, fermentable carbohydrates, dietary lipids, and phytochemical-rich foods as indirect modulators of GLP-1R activity in weight management.
KEY FINDINGS: Unlike synthetic agonists that directly bind and activate GLP-1R, dietary components primarily act through upstream nutrient-sensing and enteroendocrine pathways, including free fatty acid receptors (FFARs), the calcium-sensing receptor (CaSR), and Takeda G protein-coupled bile acid receptor 1 (TGR5), while additional mechanisms involve gut microbiota modulation, short-chain fatty acid production, delayed gastric emptying, and partial inhibition of dipeptidyl peptidase-4 (DPP-4). Evidence from clinical, preclinical, and translational studies demonstrates that dietary interventions can enhance endogenous GLP-1 secretion, improve satiety, reduce postprandial glycaemia, and support modest weight reduction. However, responses remain variable and generally less potent than pharmacological GLP-1R agonism CONCLUSION: Collectively, current findings support natural dietary components as physiologically relevant indirect modulators of GLP-1R signaling that may complement pharmacological therapies and contribute to sustainable long-term weight management. Further well-controlled human studies are required to clarify receptor-specific mechanisms, optimize dietary strategies, and strengthen translational applicability.