Nutrients, Vol. 18, Pages 1482: Protein Restriction Increases Soluble Leptin Receptor via a Leptin-Dependent Mechanism Without Affecting Leptin-Induced Appetite Suppression in Mice
Nutrients doi: 10.3390/nu18101482
Authors:
Mizuki Uchiyama
Tamaki Toyama
Yu Takei
Hinata Ishii
Asako Takenaka
Background/Objectives: Leptin, an adipocyte-derived hormone, suppresses appetite and regulates adiposity. Its soluble receptor (sOb-R), generated from the extracellular domain of the leptin receptor (Ob-R), circulates as a leptin-binding protein. We previously demonstrated that dietary protein restriction increased hepatic Ob-R mRNA expression and plasma sOb-R levels in C57BL/6J mice. However, the mechanism underlying this increase and its physiological relevance remain unclear. This study aimed to determine whether leptin is required for the protein-restriction-induced rise in circulating sOb-R and to evaluate whether elevated sOb-R modifies leptin responsiveness. Methods: C57BL/6J and ob/ob mice were fed a low-protein diet to assess the effects on hepatic Ob-R expression and plasma sOb-R levels. To examine whether increased sOb-R affects leptin action, exogenous leptin was administered to both strains under control and protein-restricted conditions, and appetite responses were evaluated. Results: Protein restriction increased hepatic Ob-R mRNA expression in both strains. Plasma sOb-R levels were elevated in C57BL/6J mice but not in ob/ob mice, indicating that endogenous leptin is essential for the protein-restriction-induced increase in circulating sOb-R. The anorexigenic effect of exogenous leptin was not altered by protein restriction in either strain. Conclusions: Protein restriction elevates circulating sOb-R through a leptin-dependent mechanism; however, this increase does not modify leptin-induced appetite suppression. These findings provide insight into the regulation of sOb-R under protein-restricted conditions.
Background/Objectives: Leptin, an adipocyte-derived hormone, suppresses appetite and regulates adiposity. Its soluble receptor (sOb-R), generated from the extracellular domain of the leptin receptor (Ob-R), circulates as a leptin-binding protein. We previously demonstrated that dietary protein restriction increased hepatic Ob-R mRNA expression and plasma sOb-R levels in C57BL/6J mice. However, the mechanism underlying this increase and its physiological relevance remain unclear. This study aimed to determine whether leptin is required for the protein-restriction-induced rise in circulating sOb-R and to evaluate whether elevated sOb-R modifies leptin responsiveness. Methods: C57BL/6J and ob/ob mice were fed a low-protein diet to assess the effects on hepatic Ob-R expression and plasma sOb-R levels. To examine whether increased sOb-R affects leptin action, exogenous leptin was administered to both strains under control and protein-restricted conditions, and appetite responses were evaluated. Results: Protein restriction increased hepatic Ob-R mRNA expression in both strains. Plasma sOb-R levels were elevated in C57BL/6J mice but not in ob/ob mice, indicating that endogenous leptin is essential for the protein-restriction-induced increase in circulating sOb-R. The anorexigenic effect of exogenous leptin was not altered by protein restriction in either strain. Conclusions: Protein restriction elevates circulating sOb-R through a leptin-dependent mechanism; however, this increase does not modify leptin-induced appetite suppression. These findings provide insight into the regulation of sOb-R under protein-restricted conditions. Read More