ArticleThe Journal of endocrinology2026
Three cholecystokinin receptors differentially regulate reproduction, digestion, lipid metabolism and growth in medaka.
Article in The Journal of endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Cholecystokinin (Cck) is a multifunctional peptide hormone involved in the regulation of digestion, appetite, and reproduction. In this study, we generated medaka (Oryzias latipes) knockout lines for three distinct Cck receptors (cck1r -/-, cck2ra -/-, and cck2rb -/-) and conducted phenotypic analysis to elucidate their physiological functions. The cck1r -/- fish exhibited markedly reduced digestive enzyme secretion and growth remained impaired until 98 days post-hatching (dph), indicating an essential role for Cck1r in digestive regulation and early development. The cck2ra -/- fish showed a slight reduction in reproductive capacity and a moderate increase in lipid accumulation, implicating its involvement in reproductive maturation and lipid metabolism. The cck2rb -/- fish exhibited complete female infertility, pronounced lipid accumulation, and enhanced somatic growth after 126 dph, suggesting a central role for Cck2rb in regulating lipid metabolism, reproduction, and body size. Transcriptomic analysis further supported receptor-specific roles in lipid metabolism and growth regulation. These findings reveal novel functions of Cck receptors in lipid metabolism and somatic growth, extending beyond their established roles in digestion and reproduction. This study provides insights into endocrine-metabolic integration in vertebrates and represents the first functional characterization of all three Cck receptor subtypes within a single vertebrate model.
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